Squamous Cell Carcinoma of Head and NeckPhase 1NCT05121948
A Study of HC-7366 to Establish the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
A Phase 1 study testing HC-7366 in people with Squamous Cell Carcinoma of Head and Neck and Colo-rectal Cancer, run by HiberCell, Inc. at 7 sites in United States.
Trial summary
This is a first in human, multicenter, open label, Phase 1a and 1b dose-escalation and dose-expansion study to establish the maximum tolerated dose, recommended Phase 2 dose, and evaluate the safety and tolerability of QD oral dosing of HC 7366 in a dose escalating fashion in subjects with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of Head and Neck, Colo-rectal Cancer, Non Small Cell Lung Cancer
- What is being tested?
- HC-7366
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 7 sitesUnited States
- Study dates
- 23 Feb 2022to 1 Mar 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a signed an informed consent form prior to any study specific procedures or treatment
- Be ≥18 years of age (male or female) at the time of consent
- Phase 1a:
- Have 1 of the following tumor types with qualifying characteristics, and have received at least 1 and no more than 5 prior lines of therapy for metastatic (stage IV) disease:
- SCCHN
- CRC
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- NSCLC
- TCC
- Other solid tumors (eg, carcinoma of unknown primary) with the exception of rapidly progressing neoplasms (eg, pancreatic cancer, glioblastoma, hepatocellular carcinoma). Note: Subjects do not need to have progressed through all possible available therapies with known clinical benefit for their respective cancers to participate in this study. Note: Subjects with SCCHN, CRC, NSCLC, and TCC are a priority and should constitute as a whole, at least 50% of the enrolled population. Enrollment of all others will be capped when reaching a combined 50%, in order to maintain 18 slots for subjects with SCCHN, CRC, NSCLC, and TCC.
- Phase 1b:
- Have renal cell carcinoma with respective qualifying characteristics:
- Histological or cytological proof of component (any percentage) of clear cell RCC, excluding subjects that have any component of collecting duct or medullary histology are eligible
- Subjects with residual, but well-controlled endocrinopathy (eg, hypothyroidism) are eligible
- Subjects with metastatic or locally advanced unresectable RCC Note: Prior nephrectomy is not mandatory.
- Subjects with progressive disease after receipt of at least 2 and no more than 5 prior lines of therapy for metastatic (stage IV) disease, including but not limited to VEGF-directed tyrosine kinase inhibitors (TKIs), high-dose IL-2 , immune checkpoint inhibitors, mTOR inhibitors, or belzutifan, alone or in combination. Note: A line of therapy is considered complete once the patient has progressed following such treatment. If a treatment regimen is changed before disease progression due to toxicity, for example, this is still considered part of the same line of therapy. In addition, maintenance therapy [that is, therapy with a different drug or drugs given to conserve an existing response or stable disease before disease progression] is not considered an additional line of therapy.
- Have at least 1 radiologically measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 defined as a lesion that is at least 10 mm in longest diameter or lymph node that is at least 15 mm in short axis imaged by CT scan or magnetic resonance imaging and obtained by imaging within 28 days prior to study treatment. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
- Have resolution of all previous treatment related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (≤Grade 2) and alopecia. If the subject received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention
- If subjects were previously treated with immune checkpoint inhibitors, at least 4 weeks must have elapsed since the last dose, and they must have recovered from toxicities as mentioned in above Criterion #5
- Subjects must have at least one biopsiable lesion at baseline. Biopsies in this clinical study will conform to American Society of Clinical Oncology's Ethical Framework for Including Research Biopsies in Oncology Clinical Trials. Provided there are suitable and accessible lesions, no biopsy contraindications, minimal risk of complications and a positive informed decision, subjects are willing to provide fresh tissue for biomarker analysis, and, based on the adequacy of the tissue sample quality, for assessment of biomarker status. Two biopsies will be necessary: at baseline (within 15 days prior to study Day 1) and at the time of the first response assessment CT scan at Cycle 3/Day 1 (+7 days). Newly obtained biopsy specimens are preferred to archived samples and formalin fixed, paraffin embedded block specimens are preferred to slides. Biopsies should not be taken from target lesions
- Have Eastern Cooperative Oncology Group performance status of 0 or 1 and sustained between screening and initiation of dosing on Day 1
- Have no swallowing difficulties that would prevent compliance with oral dosing
- Have not experienced >10% body weight loss in the previous 4 weeks
- Have a serum albumin level >3 g/dL
- Have life expectancy of 3 months or greater as determined by the treating physician
- Have adequate organ function on Day 1, as defined by meeting all of the following criteria:
- Total bilirubin ≤1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5 x ULN
- Aspartate aminotransferase and alanine aminotransferase ≤2.5 × ULN or ≤5 × ULN for subjects with known hepatic metastases
- Have adequate renal function on Day 1, as defined by creatinine ≤1.5 × ULN and creatinine clearance ≥60 mL/min, as per the below Cockcroft Gault formula
- Have adequate hematologic function on Day 1, as defined by meeting all of the following criteria:
- Hemoglobin ≥9 g/dL (uncorrected by red blood cell transfusion or erythropoietin support)
- Absolute neutrophil count ≥1.5 × 109/L
- Platelet count ≥100 × 109/L
- Have adequate coagulation function on Day 1, as defined by either of the following criteria:
- International normalized ratio (INR) <1.5 × ULN OR for subjects receiving warfarin or low molecular weight heparin, the subject must, in the investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.5 × ULN if that is the goal of anticoagulant therapy
- Activated partial thromboplastin time <1.5 × ULN unless subject is receiving anticoagulant therapy, provided prothrombin time or partial thromboplastin time is within therapeutic range of intended use of anticoagulants
- Have normal or adequately controlled pan-endocrine function (pituitary, adrenal, thyroid, pancreatic, gonadal). Subjects on hormonal supplementation must be stable at their treatment doses
- Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subjects of childbearing potential must be willing to use an adequate form of contraception from the signing of the ICF until 90 days after the last dose of study medication
- Female subjects must agree not to breastfeed and not to donate ova starting at screening and throughout the study treatment, and for 90 days after the final administration of study drug
- Male subjects with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or for the time their partner is breastfeeding throughout the study treatment and for 90 days after the final administration of study drug
- Male subjects must not donate sperm during the treatment period and for at least 90 days after the final administration of the study drug
- Male subjects with female partner(s) of child bearing potential must agree to use a condom with spermicide during the treatment period and for at least 90 days after the final administration of the study drug
- Be willing and have the ability to comply with scheduled visits (including geographical proximity), treatment plans, laboratory tests, and other study procedures.
Who cannot join
- Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study treatment or who has not recovered from adverse reactions due to a previously administered agent or major surgery
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the sponsor
- Has known history of active tuberculosis
- Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Has known active hepatitis B (eg, hepatitis B surface antigen reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid [RNA] [qualitative]) infection
Show all 19Show fewer
- Has been diagnosed with any infectious process that would, in the opinion of the investigator, interfere with study participation, especially regarding site-specific testing and isolation requirements. This applies to viral infections including, but not limited to, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection
- Has a history of clinically severe autoimmune disease, or history of organ transplant
- Has a history of retinitis or photosensitive skin disorders including (but not limited to) erythema multiforme, atopic eczema, psoriasis, viral exanthemata, pemphigus, and dermatitis herpetiformis
- Has known additional malignancy that is progressing or required active treatment within the previous 5 years. Exceptions include basal cell carcinoma or squamous cell carcinoma of the skin that has undergone potentially curative therapy, superficial bladder cancer, or in situ cervical cancer. Subjects with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease free for at least 5 years
- Has known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of disease progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using systemic steroids for at least 7 days prior to study treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
- Has a history of interstitial lung disease, pneumonitis within 12 months prior to screening, or current pneumonitis
- Has an active infection requiring systemic therapy
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Has a clinically significant cardiovascular disease such as unstable angina, myocardial infarction, or acute coronary syndrome, symptomatic or uncontrolled arrhythmia, congestive heart failure, baseline electrocardiogram (ECG) abnormalities, including, but not limited to, QTc prolongation (as calculated using Fridericia formula) to greater than 450 ms for males or to greater than 470 ms for females, or any Class III or IV cardiac disease as defined by the New York Heart Association Functional Classification
- Has overt or latent disorders of the exocrine pancreas (such as acute or chronic pancreatitis of any etiology) or chronic (including autoimmune) gastrointestinal disorders such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, lupus, scleroderma, Sjogren's syndrome, and polyarteritis nodosa
- Has a known psychiatric or substance abuse disorder(s) that would interfere with informed consent or cooperation with the requirements of the study
- Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through 90 days after the final administration of the study drug
- Is a first degree relative of the investigator, staff, or study sponsor.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Sarah Cannon Research Institute /Tennessee Oncology
Nashville, Tennessee, 37203
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Swedish Cancer Institute
Seattle, Washington, 98104
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Multicenter, Open-label, Phase 1a/b Study of HC-7366 in Subjects With Advanced Solid Tumors
This is a first in human, multicenter, open label, Phase 1a and 1b dose-escalation and dose-expansion study to establish the maximum tolerated dose, recommended Phase 2 dose, and evaluate the safety and tolerability of QD oral dosing of HC 7366 in a dose escalating fashion in subjects with advanced solid tumors. Up to 40 subjects will be enrolled into the Phase 1a dose-escalation part of the study. The study will be conducted in the United States at approximately 7 to 10 sites. Every effort will be made to ensure approximately 50% of all subjects enrolled into Phase 1a of this study are subjects with the tumors of special interest including squamous cell carcinoma of the head and neck, colorectal cancer, non-small cell lung cancer, and transitional cell carcinoma of the bladder. Subjects with other solid tumor types are also eligible provided study selection criteria are met and they do not exceed 50% of all enrolled subjects. All subjects in Phase 1b will enroll with clear cell renal cell carcinoma. The Phase 1a study will follow a traditional 3+3 design. The starting dose level will be 10 mg QD, escalating to 20, 40, 75, 125, and 150 mg QD as safety allows. All doses are to be administered in the fasting state with water at least 1 hour before food or at least 2 hours after food. The Phase 1b dose-expansion will be at a single dose level of 75 mg based on the safety, tolerability, PK/PD results from Phase 1a to obtain additional safety and preliminary efficacy information. At the discretion of the safety monitoring committee and sponsor, the cohort may be expanded to enroll additional patients and/ or 1-2 additional cohorts will be opened. Up to 30 subjects may be enrolled in the Phase 1b portion of the study at the 75 mg dose. Replacement patients will be enrolled if necessary. Subjects will be dosed until unacceptable toxicity, disease progression per immune-related Response Evaluation Criteria in Solid Tumors, discontinuation of treatment for other protocol allowed reason (eg, subject refusal), any other administrative reasons, or after 2 years of treatment, whichever occurs first. For scheduling purposes, dosing in Phase 1a and 1b will occur in 3 week cycles and computed tomography scans will be conducted once every 6 weeks from Cycle 1/Day 1, with the first postbaseline scan after 6 weeks of dosing (precycle 3) until confirmed disease progression, death, start of new anticancer therapy, withdrawal of consent, or end of study, whichever occurs first.
Read the detailed description
Subjects of Phase 1a and 1b are to spend Cycle 1/Day 1 (C1D1) in the clinic followed by an optional overnight stay for safety monitoring and PK sampling. Subjects will be hospitalized (optional) for administration of the first 2 doses: C1D1 and Cycle 1/Day 2 (C1D2). After the initial optional hospital stay at the start of study, subjects will be seen in the outpatient clinic on Days 8, 15, and 21 of Cycle 1 and thereafter, on the first day of each cycle for physical and laboratory assessments, adverse event (AE) and dosing compliance monitoring, and PK C3-C6; the End of Treatment visit will also be in-person in the outpatient clinic. An overnight stay for Cycle 1/Day 21 (C1D21) to C2D1 is also optional. Subjects will be allowed to go home after having a 12-hour PK sample draw in the clinic and will be asked to return to the clinic on C1D2 (for a safety check with a PK sample draw and an electrocardiogram (ECG) prior to dosing.
Subjects of Phase 1a who discontinue before the first postbaseline CT scan for reasons other than disease progression, a treatment-related AE, or dose limiting toxicity (DLT) prior to completion of the DLT evaluation period will be replaced to ensure an adequate safety assessment at each dose level. Subjects of Phase 1b who discontinue before the first postbaseline CT scan for reasons other than disease progression, or a treatment-related AE will be replaced and will be censored for efficacy; however, enrollment will continue to include enough subjects at each dose level in order to complete safety and efficacy assessments of that dose level.
Each subject in Phase 1a and 1b will be treated for a maximum of 2 years and followed for a maximum of 2 years.
Six dose-escalation levels are planned for subjects in the Phase 1a part of the study. Dose escalation will follow a traditional 3+3 design. A minimum of 3 subjects will be enrolled in each cohort sequentially, with expansion to 6 subjects in each cohort as needed to determine the DLT. For each cohort, the first subject is a sentinel subject. Sentinel subjects will be dosed and followed for 4 days to assess safety and tolerability. If deemed safe and well tolerated, the remainder of the cohort (N=2) will be enrolled. If none of the first 3 subjects in a cohort experiences a study treatment related DLT during the first 21 days (DLT evaluation period), the next cohort may be enrolled. Before applying the dose escalation rules, 3 subjects in a given dose level must have received a minimum of 75% of the planned dose and have been evaluated for toxicity, unless one or more subjects experiences a DLT within the first 21 days. If the first 3 DLT-evaluable subjects within a cohort experience no DLTs during the DLT-evaluation period, the next cohort may enroll. In the case a subject does not receive a minimum of 75% of the planned dose, for any reason other than a DLT (ie, lost to follow-up), the subject may be replaced. DLT's will be reviewed by the Safety Monitoring Committee (SMC) when the planned number of subjects of Phase 1a part of the study complete their DLT observation period using the dose-escalation rules. If the MTD is not reached even at the maximum dose level (150 mg QD is well tolerated), a higher dose level may be evaluated based on the SMC recommendations after a comprehensive review of the safety, PK, and efficacy data generated from the study.
- Conditions
- Squamous Cell Carcinoma of Head and Neck, Colo-rectal Cancer, Non Small Cell Lung Cancer, Transitional Cell Carcinoma of the Bladder, Other Solid Tumors, Clear Cell Renal Cell Carcinoma
- Being tested
- HC-7366
- Keywords
- SCCHN, CRC, NSCLC, TCC, Phase 1, First in human, HC-7366, ccRCC
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Colonic Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HC-7366Drug
HC-7366 drug product is an immediate release capsule formulation of HC-7366 potassium salt monohydrate (HC-7366-K) in a hard gelatin capsule for oral administration. Each capsule contains HC-7366-K monohydrate (the active ingredient), lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate. Capsules are supplied in 3 strengths: 10, 25, and 100 mg HC-7366 free acid equivalent.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1a Cohort 1 - 10 mg | Experimental | 10 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle Receives: Drug: HC-7366 |
| Phase 1a Cohort 2 - 20 mg | Experimental | 20 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle Receives: Drug: HC-7366 |
| Phase 1a Cohort 3 - 40 mg | Experimental | 40 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle Receives: Drug: HC-7366 |
| Phase 1a Cohort 4 - 75 mg | Experimental | 75 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle Receives: Drug: HC-7366 |
| Phase 1a Cohort 5 - 125 mg | Experimental | 125 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle Receives: Drug: HC-7366 |
| Phase 1a Cohort 6 - 150 mg | Experimental | 150 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle Receives: Drug: HC-7366 |
| Phase 1b Cohort 7 - Dose 1 Chosen for Expansion | Experimental | XX mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle Receives: Drug: HC-7366 |
| Phase 1b Cohort 8 - Dose 2 Chosen for Expansion | Experimental | XX mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle Receives: Drug: HC-7366 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of MTD of HC-7366
When orally administered once daily in a dose escalating fashion in subjects with selected, advanced solid tumors
Measured: Within 18 months of last patient enrolled
Determination of Recommended Phase 2 dose of HC-7366
When orally administered once daily in a dose escalating fashion in subjects with selected, advanced solid tumors
Measured: Within 18 months of last patient enrolled
Occurrence of dose-limiting toxicities (DLTs)
Measured: Within 18 months of last patient enrolled
Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment related TEAEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0
Measured: Within 18 months of last patient enrolled
Incidence of TEAEs leading to premature discontinuation
Measured: Within 18 months of last patient enrolled
Incidence of laboratory abnormalities, based on NCI CTCAE grades of hematology, serum chemistry, and urinalysis test results
Measured: Within 18 months of last patient enrolled
Incidence of abnormalities observed in 12 lead ECG parameters
Measured: Within 18 months of last patient enrolled
Incidence of abnormalities observed in vital signs measurements
Measured: Within 18 months of last patient enrolled
Secondary outcomes (16)
Area under the plasma concentration versus time curve from time 0 until last measurable concentration (AUC 0-last)
Measured: Within 24 months of last patient enrolled
Area under the plasma concentration versus time curve from time 0 to 24 hours postdose (AUC 0-24)
Measured: Within 24 months of last patient enrolled
Area under the plasma concentration versus time curve from time 0 extrapolated to infinity (AUC 0-∞)
Measured: Within 24 months of last patient enrolled
Area under the plasma concentration versus time curve over a dosing interval (AUC 0-t)
Measured: Within 24 months of last patient enrolled
Peak plasma concentration (Cmax)
Measured: Within 24 months of last patient enrolled
Time of the maximum observed plasma concentration (tmax)
Measured: Within 24 months of last patient enrolled
Apparent total clearance (CL/F) of plasma concentration
Measured: Within 24 months of last patient enrolled
Apparent volume of distribution during the terminal phase (Vz/F) of plasma concentration
Measured: Within 24 months of last patient enrolled
Apparent terminal elimination half life (t1/2) of plasma concentration
Measured: Within 24 months of last patient enrolled
Accumulation ratio based on AUC 0-t (ARAUC) of plasma concentration
Measured: Within 24 months of last patient enrolled
Linearity ratio (LR) of plasma concentration
Measured: Within 24 months of last patient enrolled
Overall response rate (ORR) to HC-7366 using iRECIST
Measured: Within 24 months of last patient enrolled
Duration of response (DOR) to HC-7366 using iRECIST
Measured: Within 24 months of last patient enrolled
Time to treatment failure (TTF)
Measured: Within 24 months of last patient enrolled
Progression-free survival (PFS) using iRECIST
Measured: Within 24 months of last patient enrolled
Overall survival (OS)
Measured: Within 24 months of last patient enrolled
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2021
- Study start23 Feb 2022
- Primary completion9 Feb 2024
- Study completion1 Mar 2024
Why it stopped: sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Carcinoma of Head and NeckStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- HiberCell, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Covance
- Responsible party
- Sponsor
- Investigators
- Jose Iglesias, MD, Study director, Consultant Chief Medical Officer for HiberCell, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05121948
- Sponsor's protocol ID
- HC366-FCP2111
- Status last verified
- Mar 2024
- First submitted
- 5 Nov 2021
- Last updated
- 8 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label, Phase 1a/b Study of HC-7366 in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT05121948
- Acronym / sponsor ID
- HC366-FCP2111
- Conditions
- Squamous Cell Carcinoma of Head and Neck, Colo-rectal Cancer, Non Small Cell Lung Cancer, Transitional Cell Carcinoma of the Bladder, Other Solid Tumors, Clear Cell Renal Cell Carcinoma
- Keywords
- SCCHN, CRC, NSCLC, TCC, Phase 1, First in human, HC-7366, ccRCC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: sponsor decision
- Enrolment
- 35 participants (actual)
- Lead sponsor
- HiberCell, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Covance
- Study start
- 23 Feb 2022 (actual)
- Primary completion
- 9 Feb 2024 (actual)
- Study completion
- 1 Mar 2024 (actual)
- First posted
- 16 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a first in human, multicenter, open label, Phase 1a and 1b dose-escalation and dose-expansion study to establish the maximum tolerated dose, recommended Phase 2 dose, and evaluate the safety and tolerability of QD oral dosing of HC 7366 in a dose escalating fashion in subjects with advanced solid tumors. Up to 40 subjects will be enrolled into the Phase 1a dose-escalation part of the study. The study will be conducted in the United States at approximately 7 to 10 sites. Every effort will be made to ensure approximately 50% of all subjects enrolled into Phase 1a of this study are subjects with the tumors of special interest including squamous cell carcinoma of the head and neck, colorectal cancer, non-small cell lung cancer, and transitional cell carcinoma of the bladder. Subjects with other solid tumor types are also eligible provided study selection criteria are met and they do not exceed 50% of all enrolled subjects. All subjects in Phase 1b will enroll with clear cell renal cell carcinoma. The Phase 1a study will follow a traditional 3+3 design. The starting dose level will be 10 mg QD, escalating to 20, 40, 75, 125, and 150 mg QD as safety allows. All doses are to be administered in the fasting state with water at least 1 hour before food or at least 2 hours after food. The Phase 1b dose-expansion will be at a single dose level of 75 mg based on the safety, tolerability, PK/PD results from Phase 1a to obtain additional safety and preliminary efficacy information. At the discretion of the safety monitoring committee and sponsor, the cohort may be expanded to enroll additional patients and/ or 1-2 additional cohorts will be opened. Up to 30 subjects may be enrolled in the Phase 1b portion of the study at the 75 mg dose. Replacement patients will be enrolled if necessary. Subjects will be dosed until unacceptable toxicity, disease progression per immune-related Response Evaluation Criteria in Solid Tumors, discontinuation of treatment for other protocol allowed reason (eg, subject refusal), any other administrative reasons, or after 2 years of treatment, whichever occurs first. For scheduling purposes, dosing in Phase 1a and 1b will occur in 3 week cycles and computed tomography scans will be conducted once every 6 weeks from Cycle 1/Day 1, with the first postbaseline scan after 6 weeks of dosing (precycle 3) until confirmed disease progression, death, start of new anticancer therapy, withdrawal of consent, or end of study, whichever occurs first.
Detailed description
Subjects of Phase 1a and 1b are to spend Cycle 1/Day 1 (C1D1) in the clinic followed by an optional overnight stay for safety monitoring and PK sampling. Subjects will be hospitalized (optional) for administration of the first 2 doses: C1D1 and Cycle 1/Day 2 (C1D2). After the initial optional hospital stay at the start of study, subjects will be seen in the outpatient clinic on Days 8, 15, and 21 of Cycle 1 and thereafter, on the first day of each cycle for physical and laboratory assessments, adverse event (AE) and dosing compliance monitoring, and PK C3-C6; the End of Treatment visit will also be in-person in the outpatient clinic. An overnight stay for Cycle 1/Day 21 (C1D21) to C2D1 is also optional. Subjects will be allowed to go home after having a 12-hour PK sample draw in the clinic and will be asked to return to the clinic on C1D2 (for a safety check with a PK sample draw and an electrocardiogram (ECG) prior to dosing.
Subjects of Phase 1a who discontinue before the first postbaseline CT scan for reasons other than disease progression, a treatment-related AE, or dose limiting toxicity (DLT) prior to completion of the DLT evaluation period will be replaced to ensure an adequate safety assessment at each dose level. Subjects of Phase 1b who discontinue before the first postbaseline CT scan for reasons other than disease progression, or a treatment-related AE will be replaced and will be censored for efficacy; however, enrollment will continue to include enough subjects at each dose level in order to complete safety and efficacy assessments of that dose level.
Each subject in Phase 1a and 1b will be treated for a maximum of 2 years and followed for a maximum of 2 years.
Six dose-escalation levels are planned for subjects in the Phase 1a part of the study. Dose escalation will follow a traditional 3+3 design. A minimum of 3 subjects will be enrolled in each cohort sequentially, with expansion to 6 subjects in each cohort as needed to determine the DLT. For each cohort, the first subject is a sentinel subject. Sentinel subjects will be dosed and followed for 4 days to assess safety and tolerability. If deemed safe and well tolerated, the remainder of the cohort (N=2) will be enrolled. If none of the first 3 subjects in a cohort experiences a study treatment related DLT during the first 21 days (DLT evaluation period), the next cohort may be enrolled. Before applying the dose escalation rules, 3 subjects in a given dose level must have received a minimum of 75% of the planned dose and have been evaluated for toxicity, unless one or more subjects experiences a DLT within the first 21 days. If the first 3 DLT-evaluable subjects within a cohort experience no DLTs during the DLT-evaluation period, the next cohort may enroll. In the case a subject does not receive a minimum of 75% of the planned dose, for any reason other than a DLT (ie, lost to follow-up), the subject may be replaced. DLT's will be reviewed by the Safety Monitoring Committee (SMC) when the planned number of subjects of Phase 1a part of the study complete their DLT observation period using the dose-escalation rules. If the MTD is not reached even at the maximum dose level (150 mg QD is well tolerated), a higher dose level may be evaluated based on the SMC recommendations after a comprehensive review of the safety, PK, and efficacy data generated from the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Phase 1a Cohort 1 - 10 mg | Experimental | Drug: HC-736610 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle |
| Phase 1a Cohort 2 - 20 mg | Experimental | Drug: HC-736620 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle |
| Phase 1a Cohort 3 - 40 mg | Experimental | Drug: HC-736640 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle |
| Phase 1a Cohort 4 - 75 mg | Experimental | Drug: HC-736675 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle |
| Phase 1a Cohort 5 - 125 mg | Experimental | Drug: HC-7366125 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle |
| Phase 1a Cohort 6 - 150 mg | Experimental | Drug: HC-7366150 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle |
| Phase 1b Cohort 7 - Dose 1 Chosen for Expansion | Experimental | Drug: HC-7366XX mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle |
| Phase 1b Cohort 8 - Dose 2 Chosen for Expansion | Experimental | Drug: HC-7366XX mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (43 listed)
- Have a signed an informed consent form prior to any study specific procedures or treatment
- Be ≥18 years of age (male or female) at the time of consent
- Phase 1a:
- Have 1 of the following tumor types with qualifying characteristics, and have received at least 1 and no more than 5 prior lines of therapy for metastatic (stage IV) disease:
- Have at least 1 radiologically measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 defined as a lesion that is at least 10 mm in longest diameter or lymph node that is at least 15 mm in short axis imaged by CT scan or magnetic resonance imaging and obtained by imaging within 28 days prior to study treatment. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
Key exclusion criteria (19 listed)
- Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study treatment or who has not recovered from adverse reactions due to a previously administered agent or major surgery
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the sponsor
- Has known history of active tuberculosis
- Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HC-7366HC-7366 drug product is an immediate release capsule formulation of HC-7366 potassium salt monohydrate (HC-7366-K) in a hard gelatin capsule for oral administration. Each capsule contains HC-7366-K monohydrate (the active ingredient), lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate. Capsules are supplied in 3 strengths: 10, 25, and 100 mg HC-7366 free acid equivalent. | Drug | Phase 1a Cohort 1 - 10 mg, Phase 1a Cohort 2 - 20 mg, Phase 1a Cohort 3 - 40 mg, Phase 1a Cohort 4 - 75 mg, Phase 1a Cohort 5 - 125 mg, Phase 1a Cohort 6 - 150 mg, Phase 1b Cohort 7 - Dose 1 Chosen for Expansion, Phase 1b Cohort 8 - Dose 2 Chosen for Expansion |
Primary outcome
Determination of MTD of HC-7366
Time frame: Within 18 months of last patient enrolled
When orally administered once daily in a dose escalating fashion in subjects with selected, advanced solid tumors
Determination of Recommended Phase 2 dose of HC-7366
Time frame: Within 18 months of last patient enrolled
When orally administered once daily in a dose escalating fashion in subjects with selected, advanced solid tumors
Occurrence of dose-limiting toxicities (DLTs)
Time frame: Within 18 months of last patient enrolled
Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment related TEAEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0
Time frame: Within 18 months of last patient enrolled
Incidence of TEAEs leading to premature discontinuation
Time frame: Within 18 months of last patient enrolled
Incidence of laboratory abnormalities, based on NCI CTCAE grades of hematology, serum chemistry, and urinalysis test results
Time frame: Within 18 months of last patient enrolled
Incidence of abnormalities observed in 12 lead ECG parameters
Time frame: Within 18 months of last patient enrolled
Incidence of abnormalities observed in vital signs measurements
Time frame: Within 18 months of last patient enrolled
16 secondary outcomes
Area under the plasma concentration versus time curve from time 0 until last measurable concentration (AUC 0-last)
Time frame: Within 24 months of last patient enrolled
Area under the plasma concentration versus time curve from time 0 to 24 hours postdose (AUC 0-24)
Time frame: Within 24 months of last patient enrolled
Area under the plasma concentration versus time curve from time 0 extrapolated to infinity (AUC 0-∞)
Time frame: Within 24 months of last patient enrolled
Area under the plasma concentration versus time curve over a dosing interval (AUC 0-t)
Time frame: Within 24 months of last patient enrolled
Peak plasma concentration (Cmax)
Time frame: Within 24 months of last patient enrolled
Time of the maximum observed plasma concentration (tmax)
Time frame: Within 24 months of last patient enrolled
Apparent total clearance (CL/F) of plasma concentration
Time frame: Within 24 months of last patient enrolled
Apparent volume of distribution during the terminal phase (Vz/F) of plasma concentration
Time frame: Within 24 months of last patient enrolled
Apparent terminal elimination half life (t1/2) of plasma concentration
Time frame: Within 24 months of last patient enrolled
Accumulation ratio based on AUC 0-t (ARAUC) of plasma concentration
Time frame: Within 24 months of last patient enrolled
Linearity ratio (LR) of plasma concentration
Time frame: Within 24 months of last patient enrolled
Overall response rate (ORR) to HC-7366 using iRECIST
Time frame: Within 24 months of last patient enrolled
Duration of response (DOR) to HC-7366 using iRECIST
Time frame: Within 24 months of last patient enrolled
Time to treatment failure (TTF)
Time frame: Within 24 months of last patient enrolled
Progression-free survival (PFS) using iRECIST
Time frame: Within 24 months of last patient enrolled
Overall survival (OS)
Time frame: Within 24 months of last patient enrolled
Results and safety
The study was stopped early (reason given: sponsor decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jose Iglesias, MD study director
Consultant Chief Medical Officer for HiberCell, Inc.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HC-7366 in people with Squamous Cell Carcinoma of Head and Neck and Colo-rectal Cancer, run by HiberCell, Inc. at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 43 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: sponsor decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of MTD of HC-7366 (time frame: Within 18 months of last patient enrolled). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2024.