Breast CancerPhase 1NCT02569489
Dose Escalation Study of HBI-8000 in Combination With Paclitaxel and Trastuzumab in Women With Advanced or Metastatic HER2+ Breast Cancer
A Phase 1 study testing HBI-8000, Trastuzumab and Paclitaxel in people with Breast Cancer, run by HUYABIO International, LLC..
Trial summary
This is a phase I multi-center dose escalation study of the histone deacetylase inhibitor (HDACi) HBI-8000 when given in combination with paclitaxel and trastuzumab in women with advanced or metastatic HER2+ breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- HBI-8000, Trastuzumab and Paclitaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2015to Dec 2015
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female subject, age ≥18 years at the time of signing informed consent
- Histologically or cytologically confirmed adenocarcinoma of breast, HER2+ as determined by FISH or IHC
- Having received at least one prior systemic therapy with FDA approved agent(s) for metastatic disease and have no curative option
- Measureable disease as defined by RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Laboratory parameters within 14 days prior to dosing:
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- Absolute neutrophil count (ANC) ≥ 1.5 X 109/L independent of growth factor support
- Hemoglobin (Hgb) ≥9 gm/dL independent of transfusion or growth factor support
- Platelets (plt) ≥ 100 x 109/L independent of transfusion or growth factor support
- AST and ALT ≤2.5 x Upper Limit of Normal (ULN); if hepatic metastasis is present, ≤2.5 x ULN
- Serum total bilirubin ≤ 1.5 x ULN; if with Gilbert's Syndrome, direct bilirubin must be normal
- Serum creatinine ≤ 1.5 x ULN or eGFR ≥ 60ml/min
- Serum albumin > 3.0 g/dL
- Prothrombin time (PT)/International normalized ratio (INR) ≤ 1.5, partial thromboplastin time (PTT) within normal limits (WNL) of the institution
- Negative serum pregnancy test in subjects with child-bearing potential; and commit to abstinence or comply with medically proven contraception methods
- Agree to abstain from breast feeding from the start of study treatment and >28 days after the last dose of study drugs.
- Understand and voluntarily sign informed consent
Who cannot join
- Receiving chemotherapy, immunotherapy, biological, radiation therapy or investigational agent (therapeutic or diagnostic) within 4 weeks prior to receipt of study medication. Major surgery, other than diagnostic surgery, within 4 weeks before first study drug administration.
- Significant cardiac history:
- History of myocardial infarction or ischemic heart disease within 1 year before the first study drug administration
- Uncontrolled arrhythmia, such as ventricular tachycardia, ventricular fibrillation; second- or third-degree heart block; unstable angina, coronary angioplasty or stenting, or myocardial infarction (MI) within 6 months of study entry
- History of congenital QT prolongation, or baseline QTcF > 470 ms using Fridericia's formula
- ECG findings consistent with active ischemic heart disease
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- New York Heart Association Class III or IV cardiac disease
- Left ventricular Ejection Fraction measuring ≥ 55% at baseline ECHO
- Uncontrolled hypertension: blood pressure consistently greater than 150 mm Hg systolic and 100 mm Hg diastolic in spite of antihypertensive medication
- Patients with active brain metastasis or leptomeningeal involvement. Patients who have brain metastases that have been previously treated, who are asymptomatic, and whose lesions by imaging are at least stable and without interim development of new lesions for at least 6 weeks may be enrolled. Patients who require continued steroid therapy as management for their brain metastases are not eligible
- Persistent diarrhea or malabsorption NCI CTCAE (version 4.03) grade ≥ 1 despite medical management, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting GI function
- Peripheral neuropathy NCI CTCAE (Version 4.03) Grade ≥ 2
- Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
- Known infection with human immunodeficiency virus (HIV) or active hepatitis A, B, or C.
- Patients with a prior hypersensitivity reaction to any product containing polyvinylpyrrolidone, microcrystalline cellulose, lactose monohydrate, sodium starch glycolate, talc or magnesium stearate.
- Second malignancy unless in remission for > 5 years. (Non-melanoma skin cancer or carcinoma in situ of the cervix treated with curative intent is not exclusionary.)
- Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient. Examples of such conditions include infection requiring parenteral anti-infective treatment, hydronephrosis, liver failure, any altered mental status or any psychiatric condition that would interfere with the understanding of the informed consent.
- Unwilling or unable to comply with procedures required in this protocol.
About this study
Official title: Phase I Dose Escalation Study of HBI-8000 in Combination With Paclitaxel and Trastuzumab in Women With Advanced or Metastatic HER2+ Breast Cancer
This is a phase I multi-center dose escalation study of the histone deacetylase inhibitor (HDACi) HBI-8000 when given in combination with paclitaxel and trastuzumab in women with advanced or metastatic HER2+ breast cancer.
Read the detailed description
This is a phase I multi-center dose escalation study of the histone deacetylase inhibitor (HDACi) HBI-8000 when given in combination with paclitaxel and trastuzumab in women with advanced or metastatic HER2+ breast cancer.
Three dose levels of HBI-8000 (15 mg, 20 mg, and 25 mg) will be tested using a standard 3+3 escalation plan with an expanded cohort at the maximum tolerated dose (MTD) to enroll a minimum of 10 patients evaluable for safety to fulfill the requirements for moving the combination forward to I-SPY 2 trial.
To be considered evaluable for safety, the patient must receive at least 75% of their prescribed regimen per cycle for 4 consecutive cycles with a cycle of therapy defined as 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress at 9 weeks evaluation or later but before completing 4 cycles and who have only experienced Grade ≤ 1 toxicities (excluding alopecia) will also be considered evaluable for safety.
Enrolled patients will remain on their assigned dose level until unacceptable toxicity or disease progression occurs. During dose escalation phase, if more than 34% of the evaluable patients at a dose level experience dose limiting toxicities (DLT), this dose level will be considered having exceeded MTD. Once MTD is identified during dose escalation phase, the MTD dose level will be expanded in the expansion phase to enroll additional patients to ensure that at least 10 patients are evaluable for safety at the MTD.
Paclitaxel and trastuzumab are administered by intravenous (IV) infusion on days 1, 8, 15, and 22 of a 28-day cycle. HBI-8000 will be taken by mouth twice weekly at the assigned dose on days 1, 4, 8, 11, 15, 18, 22 and 25 of a 28-day cycle. Treatment continues until disease progression, unacceptable toxicity, or patient refusal/non-compliance is observed.
The study will evaluate the safety and tolerability of oral HBI-8000 bi-weekly in combination with weekly paclitaxel and trastuzumab and if successful, determine an optimal dose to move into phase II testing of this combination in the I-SPY 2 trial in a neo-adjuvant breast cancer population.
To determine the MTD of HBI-8000 twice weekly in combination with weekly paclitaxel and trastuzumab in women with HER2+ breast cancer.
- To determine the adverse event rate of twice weekly HBI-8000 in combination with weekly paclitaxel and trastuzumab
- To determine the tolerability of twice weekly HBI-8000 when administered with weekly paclitaxel and trastuzumab
- To explore efficacy of twice weekly HBI-8000 in combination with weekly paclitaxel and trastuzumab
- To obtain pharmacokinetics of twice weekly HBI-8000 when administered in combination with weekly paclitaxel and trastuzumab.
- To determine the on-target effect of HBI-8000 by measuring protein acetylation
- To explore the treatment effects on immune cells in blood and/or tumor tissue as appropriate
Enrolled patients will take HBI-8000 at the assigned dose twice weekly while receiving weekly paclitaxel and trastuzumab for a minimum of 8 weeks (2 treatment cycles). On the day of paclitaxel infusion, HBI-8000 is taken at least one hour before paclitaxel infusion. HBI-8000 should be taken within 30 minutes after a meal. The interval between HBI-8000 administrations is 3-4 days in the absence of dose delay or interruptions due to adverse events. For example, three days should elapse between the 1st and 2nd dose of HBI-8000 of the week, such as Monday/Thursday; Tuesday/Friday.
A disease re-evaluation will be scheduled every 8 weeks. Based on the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST1.1), response to treatment will be determined. Patients with stable disease (SD), partial response (PR) or complete response (CR) may continue treatment until disease progression, unacceptable side effects, or patient refusal/non-compliance occurs.
Patients will be monitored in clinic every 4 weeks while receiving study treatment. The end of treatment (EOT) visit will occur at 4 weeks after the last dose of HBI-8000, or before the start of a new anti-cancer therapy, whichever is earlier. At EOT, patients will be evaluated for resolution of treatment related toxicities. Toxicity related to HBI-8000, if not yet resolved to Grade ≤ 1, will be followed until resolution to Grade ≤ 1 or considered chronic. All patients will be followed up to 1 year from study enrollment for best objective response, duration of response, time to PD, and survival.
- Conditions
- Breast Cancer
- Being tested
- HBI-8000, Trastuzumab, Paclitaxel
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HBI-8000Drug
TrastuzumabDrug
PaclitaxelDrug
| Study group | Role | What they receive |
|---|---|---|
| HBI-8000, Paclitaxel, Trastuzumab | Experimental | HBI-8000 at the assigned dose twice weekly while receiving weekly paclitaxel and trastuzumab for a minimum of 8 weeks (2 treatment cycles) Receives: Drug: HBI-8000; Drug: Trastuzumab; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of HBI-8000 twice weekly in combination with weekly paclitaxel and trastuzumab in women with HER2+ breast cancer
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2015 (estimated)
- Study startDec 2015 (estimated)
- Primary completionDec 2015 (estimated)
- Study completionDec 2015 (estimated)
Why it stopped: Reconsideration of Study Design; plan for alternative protocol
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- HUYABIO International, LLC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02569489
- Sponsor's protocol ID
- HBI-8000-106
- Status last verified
- Jun 2016
- First submitted
- 5 Oct 2015
- Last updated
- 18 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Escalation Study of HBI-8000 in Combination With Paclitaxel and Trastuzumab in Women With Advanced or Metastatic HER2+ Breast Cancer
- ClinicalTrials.gov ID
- NCT02569489
- Acronym / sponsor ID
- HBI-8000-106
- Conditions
- Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Reconsideration of Study Design; plan for alternative protocol
- Enrolment
- 0 participants (actual)
- Lead sponsor
- HUYABIO International, LLC.Industry (pharma, biotech, devices)
- Study start
- Dec 2015 (estimated)
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 6 Oct 2015 (estimated)
- 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 phase I multi-center dose escalation study of the histone deacetylase inhibitor (HDACi) HBI-8000 when given in combination with paclitaxel and trastuzumab in women with advanced or metastatic HER2+ breast cancer.
Detailed description
This is a phase I multi-center dose escalation study of the histone deacetylase inhibitor (HDACi) HBI-8000 when given in combination with paclitaxel and trastuzumab in women with advanced or metastatic HER2+ breast cancer.
Three dose levels of HBI-8000 (15 mg, 20 mg, and 25 mg) will be tested using a standard 3+3 escalation plan with an expanded cohort at the maximum tolerated dose (MTD) to enroll a minimum of 10 patients evaluable for safety to fulfill the requirements for moving the combination forward to I-SPY 2 trial.
To be considered evaluable for safety, the patient must receive at least 75% of their prescribed regimen per cycle for 4 consecutive cycles with a cycle of therapy defined as 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress at 9 weeks evaluation or later but before completing 4 cycles and who have only experienced Grade ≤ 1 toxicities (excluding alopecia) will also be considered evaluable for safety.
Enrolled patients will remain on their assigned dose level until unacceptable toxicity or disease progression occurs. During dose escalation phase, if more than 34% of the evaluable patients at a dose level experience dose limiting toxicities (DLT), this dose level will be considered having exceeded MTD. Once MTD is identified during dose escalation phase, the MTD dose level will be expanded in the expansion phase to enroll additional patients to ensure that at least 10 patients are evaluable for safety at the MTD.
Paclitaxel and trastuzumab are administered by intravenous (IV) infusion on days 1, 8, 15, and 22 of a 28-day cycle. HBI-8000 will be taken by mouth twice weekly at the assigned dose on days 1, 4, 8, 11, 15, 18, 22 and 25 of a 28-day cycle. Treatment continues until disease progression, unacceptable toxicity, or patient refusal/non-compliance is observed.
The study will evaluate the safety and tolerability of oral HBI-8000 bi-weekly in combination with weekly paclitaxel and trastuzumab and if successful, determine an optimal dose to move into phase II testing of this combination in the I-SPY 2 trial in a neo-adjuvant breast cancer population.
To determine the MTD of HBI-8000 twice weekly in combination with weekly paclitaxel and trastuzumab in women with HER2+ breast cancer.
- To determine the adverse event rate of twice weekly HBI-8000 in combination with weekly paclitaxel and trastuzumab
- To determine the tolerability of twice weekly HBI-8000 when administered with weekly paclitaxel and trastuzumab
- To explore efficacy of twice weekly HBI-8000 in combination with weekly paclitaxel and trastuzumab
- To obtain pharmacokinetics of twice weekly HBI-8000 when administered in combination with weekly paclitaxel and trastuzumab.
- To determine the on-target effect of HBI-8000 by measuring protein acetylation
- To explore the treatment effects on immune cells in blood and/or tumor tissue as appropriate
Enrolled patients will take HBI-8000 at the assigned dose twice weekly while receiving weekly paclitaxel and trastuzumab for a minimum of 8 weeks (2 treatment cycles). On the day of paclitaxel infusion, HBI-8000 is taken at least one hour before paclitaxel infusion. HBI-8000 should be taken within 30 minutes after a meal. The interval between HBI-8000 administrations is 3-4 days in the absence of dose delay or interruptions due to adverse events. For example, three days should elapse between the 1st and 2nd dose of HBI-8000 of the week, such as Monday/Thursday; Tuesday/Friday.
A disease re-evaluation will be scheduled every 8 weeks. Based on the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST1.1), response to treatment will be determined. Patients with stable disease (SD), partial response (PR) or complete response (CR) may continue treatment until disease progression, unacceptable side effects, or patient refusal/non-compliance occurs.
Patients will be monitored in clinic every 4 weeks while receiving study treatment. The end of treatment (EOT) visit will occur at 4 weeks after the last dose of HBI-8000, or before the start of a new anti-cancer therapy, whichever is earlier. At EOT, patients will be evaluated for resolution of treatment related toxicities. Toxicity related to HBI-8000, if not yet resolved to Grade ≤ 1, will be followed until resolution to Grade ≤ 1 or considered chronic. All patients will be followed up to 1 year from study enrollment for best objective response, duration of response, time to PD, and survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HBI-8000, Paclitaxel, Trastuzumab | Experimental | Drug: HBI-8000, Drug: Trastuzumab, Drug: PaclitaxelHBI-8000 at the assigned dose twice weekly while receiving weekly paclitaxel and trastuzumab for a minimum of 8 weeks (2 treatment cycles) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Female subject, age ≥18 years at the time of signing informed consent
- Histologically or cytologically confirmed adenocarcinoma of breast, HER2+ as determined by FISH or IHC
- Having received at least one prior systemic therapy with FDA approved agent(s) for metastatic disease and have no curative option
- Measureable disease as defined by RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
Key exclusion criteria (18 listed)
- Receiving chemotherapy, immunotherapy, biological, radiation therapy or investigational agent (therapeutic or diagnostic) within 4 weeks prior to receipt of study medication. Major surgery, other than diagnostic surgery, within 4 weeks before first study drug administration.
- Significant cardiac history:
- Patients with active brain metastasis or leptomeningeal involvement. Patients who have brain metastases that have been previously treated, who are asymptomatic, and whose lesions by imaging are at least stable and without interim development of new lesions for at least 6 weeks may be enrolled. Patients who require continued steroid therapy as management for their brain metastases are not eligible
- Persistent diarrhea or malabsorption NCI CTCAE (version 4.03) grade ≥ 1 despite medical management, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting GI function
- Peripheral neuropathy NCI CTCAE (Version 4.03) Grade ≥ 2
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 |
|---|---|---|
| HBI-8000 | Drug | HBI-8000, Paclitaxel, Trastuzumab |
| Trastuzumab | Drug | HBI-8000, Paclitaxel, Trastuzumab |
| Paclitaxel | Drug | HBI-8000, Paclitaxel, Trastuzumab |
Primary outcome
MTD of HBI-8000 twice weekly in combination with weekly paclitaxel and trastuzumab in women with HER2+ breast cancer
Time frame: 28 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2022.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HBI-8000, Trastuzumab and Paclitaxel in people with Breast Cancer, run by HUYABIO International, LLC..
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 17 inclusion and 18 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: withdrawn, as of the sponsor's last update on 18 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
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 withdrawn before enrolling participants, so there are no results.
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?
MTD of HBI-8000 twice weekly in combination with weekly paclitaxel and trastuzumab in women with HER2+ breast cancer (time frame: 28 days). 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 18 Jul 2022.