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Advanced Solid TumoursPhase 1/2NCT04434482

IMP4297 in Combination With Temozolomide in Patients With Advanced Solid Tumors and Small Cell Lung Cancer

A Phase 1/2 study testing IMP4297(senaparib) in people with Advanced Solid Tumours and Small Cell Lung Cancer, run by Impact Therapeutics, Inc. at 21 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open-label, multi-center, dose-escalation and dose-expansion phase I study to evaluate the safety, tolerability, PK characteristics and anti-tumor activity of PARP inhibitor IMP4297 and temozolomide combination therapy in patients with advanced solid tumors and with ES-SCLC who develops disease progression… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
IMP4297(senaparib)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
21 sitesin 5 countries
Study dates
7 Aug 2020to 29 Apr 2024
Phase
Phase 1/2
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

  • The patient must voluntarily participate in this clinical study and be willing and able to provide written informed consent/assent for the trial.
  • Age ≥ 18 years old on the day of signing informed consent form (ICF), males or females
  • Patient population:
  • In Part I: The patient must have histologically or cytologically confirmed advanced solid tumor that is refractory to standard treatment or for which no standard treatment exists, including but not limited to triple-negative breast cancer (TNBC), SCLC, ovarian cancer (OC) and metastatic castration-resistant prostate cancer (mCRPC).
  • In Part II: The patients must be histologically or cytologically confirmed ES-SCLC with disease progression after one and only one course of 1L standard platinum-based therapy. Anti-PD-1 or anti-PD-L1 antibody therapy is acceptable as long as it's part of the 1L treatment. Including platinum sensitive and platinum resistant patients. Platinum sensitive is defined as the relapse-free interval exceeds 90 days after treatment with platinum doublets is completed; The platinum resistant represents disease relapses within 90 days of treatment completion during a chemotherapy-free interval (CFI).
  • In Part I: Patients have an ECOG performance status of 0 to 1.
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  • In Part II: Patients have an ECOG performance status of 0 to 2.
  • Patients have a life expectancy of ≥12 weeks.
  • In Part II: patients have at least 1 measurable lesion per RECIST v1.1, including a previously irradiated lesion if has progressed since radiotherapy, that can be accurately measured at baseline which is suitable for accurate repeated measurements
  • Patients have adequate organ function, as indicated by the following laboratory values (had not received blood transfusion, apheresis infusion, erythropoietin, granulocyte colony-stimulating factor, and other relevant medical support within 28 days before the administration of the IPs
  • Female patients should meet at least 1 of the following criteria before they can participate in the study:
  • Females who have no childbearing potential (i.e., physiologically incapable of pregnancy), including those who have undergone hysterectomy, bilateral oophorectomy, or bilateral salpingectomy.
  • Post-menopausal (total cessation of menses for ≥1 year).
  • For those with childbearing potential, they should have a negative serum pregnancy test during the screening period (within 7 days prior to the first dose of the IPs), should not be in lactation, and willing to take effective contraceptive measures throughout the study period, from study entry up to 6 months after the last dose of the IP(s).
  • Male patients are eligible to participate in the study if they have undergone vasectomy or agree to use effective methods of contraception from study entry up to 6 months after the last dose of the IP(s).

Who cannot join

  • Patients with primary tumor in central nervous system (CNS) and active or untreated central CNS metastases and/or carcinomatous meningitis should be excluded. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks and, have no evidence of new or enlarging brain metastases and no requirements for corticosteroids 14 days prior to dosing with IPs.
  • Patients with serious acute and chronic infections, including:
  • Patients with an uncontrolled acute infection, or an active infection requiring systemic treatment, or patients who have received systemic antibiotics within 2 weeks prior to the first dose of the IPs; prophylaxis use of systemic antibiotics treatment for upper tract infection is allowed as long as no violation with the requirement in Section 6.5 Concomitant Therapy.
  • Patients who have a known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome or positive HIV testing should undergo CD4+ T-cell test during the screening period. Patients with CD4+ T-cell counts < 350 cells/uL are ineligible for enrollment. Patients with unknown HIV infection status who are unwilling to undergo HIV testing should not be enrolled in the study;
  • Patients who have known active hepatitis B or C. To be included in the study, patients with hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV) antibody positive test results during screening must be further tested for hepatitis B virus (HBV) DNA titer (excluding patients with a DNA titer of more than 2500 copies [cps]/mL or 500 IU/mL) and HCV RNA (excluding patients with an HCV RNA concentration exceeding the lower detection limit of the assay) to exclude active hepatitis B or hepatitis C infection requiring treatment. Hepatitis B virus carriers, patients with stable hepatitis B infection after drug treatment (DNA titer not exceeding 2500 copies [cps]/mL or 500 IU/mL) and hepatitis C infected patients who received treatment and achieved sustained virologic response for at least 12 weeks can be enrolled.
  • Note: If the lower detection limit of the HBV DNA assay in the study centers is higher than 2500 copies [cps]/mL or 500 IU/mL, the patients in the study center with an HBV DNA assay result lower than the lower detection limit of the assay can be enrolled.
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  • Active tuberculosis
  • Patients who have previously received PARP inhibitors.
  • Patients who have received strong CYP3A4 inhibitors or inducers prior to the first dose of the IPs (the patient can be enrolled if the elution period prior to the first dose of the IPs is ≥5 half-lives), or patients who need to continue receiving these medications during the study period.
  • Patients who have received a live-virus vaccination within 28 days of the planned start of study.
  • Patients who have participated a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of treatment.
  • Patients have not recovered (i.e., to ≤Grade 1 or to baseline, as evaluated by NCI-CTCAE v5.0) from cytotoxic therapy-induced AEs, except for alopecia.
  • Patients who have received anti-cancer chemotherapy, endocrine therapy, herbal/alternative therapies (including Chinese herbal or Chinese medicine or proprietary Chinese medicine), or other anti-cancer systemic treatment (except anti-cancer antibody) within 5 half-lives or 14 days, whichever is longer prior to the first dose of the IPs. Patients who have received anti-cancer antibody within 28 days prior to the first dose of the IPs.
  • Patients who have undergone a major surgery within 28 days prior to the study treatment, or have undergone a radical radiotherapy, or have undergone a palliative radiotherapy within 14 days prior to the study treatment, or have used a radioactive drug (Strontium, Samarium, etc.) within 56 days prior to the study treatment.
  • In Part II of the study, patients who have other malignancies within 2 years prior to the first dose of the IPs will be excluded. except for radically treated locally curable malignant tumors, such as basal or squamous cell skin cancer, superficial bladder cancer, or prostate, cervical or breast carcinoma in situ.
  • Patients with uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (once monthly or more frequently). Please contact medical monitor if any further discussion or clarification is needed.
  • Patients with a history of seizures.
  • Patients with a previously documented diagnosis of myelodysplastic syndrome (MDS).
  • Patients who have major cardiovascular diseases (such as congestive heart failure, unstable angina, atrial fibrillation, arrhythmia); patients who have acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to the first dose of the IPs; patients who have congestive heart failure (≥New York Heart Association [NYHA] Classification Class II); patients who have severe arrhythmia requiring medication (including QT interval [QTc] prolongation corrected by the Fridericia's formula [QTcF] of more than 480 msec, pacemaker installation, and previous diagnosis of congenital long QT syndrome).
  • Patients who are unable to swallow capsules. Patients have gastrointestinal illnesses that may affect the absorption of oral medication IMP4297 and temozolomide.
  • Patients with a known hypersensitivity to IMP4297, temozolomide or any of the excipients of the products.
  • Patients who have received transplantation including patients with previous allogeneic bone marrow transplant.
  • Patients known to have a history of alcoholism or drug abuse.
  • The investigator believes that the patient's underlying disease may put the patient at risk in IP administration or may affect the evaluation of toxicity events or AEs.

Trial locations and contacts

21 sites in 5 countries.

21 sites in 5 countries

Taiwan5 sites

  • China Medical University Hospital

    Taichung, 404

  • National Cheng Kung University Hospital

    Tainan, 704

  • Chi Mei Medical Center

    Tainan, 73657

  • National Taiwan University Hospital

    Taipei, 100

  • Chang Gung Medical Foundation Linko

    Taoyuan, 333

Other trials in Taiwan

United States4 sites

  • Gabrail Cancer Researh Center

    Canton, Ohio, 44718

  • Mark H. Zangmeister Center

    Columbus, Ohio, 43219

  • GenHarp Clinical Solutions

    Evergreen Park, Illinois, 60805

  • Sarah Cannon Research Institute - Tennessee Oncology

    Tennessee City, Tennessee, 37203

Other trials in United States

Australia4 sites

  • Border Medical Oncology

    Albury, New South Wales, 2640

  • Blacktown Hospital

    Blacktown, New South Wales, 2148

  • Peninsula Health Frankston Hospital

    Frankston, Victoria, 3199

  • Orange Hospital

    Orange, New South Wales, 2800

Other trials in Australia

China4 sites

  • Beijing Cancer Hospital

    Beijing, 100142

  • Jilin Cancer Hospital

    Jilin City, 130000

  • Fudan University Shanghai Cancer Center

    Shanghai, 200032

  • Hubei Cancer Hospital

    Wuhan, 430079

Other trials in China

South Korea4 sites

  • Chungbuk National University Hospital

    Cheongju-si, 2864

  • The Catholic university of Korea, st. Vincent's Hospital

    Gyeonggi-do, 16247

  • Yonsei university health system, Severance Hospital

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

Other trials in South Korea

About this study

Official title: A Phase Ib/II, Open-Label, Multi-Center, Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of IMP4297 in Combination With Temozolomide in Patients With Advanced Solid Tumors and Small Cell Lung Cancer

This is an open-label, multi-center, dose-escalation and dose-expansion phase I study to evaluate the safety, tolerability, PK characteristics and anti-tumor activity of PARP inhibitor IMP4297 and temozolomide combination therapy in patients with advanced solid tumors and with ES-SCLC who develops disease progression after 1L platinum-based regimen.

Read the detailed description

This study will be conducted in two parts. Part I of the study will be dose escalation evaluation to determine the MTD and/or recommended phase 2 dose（RP2D） of IMP4297 in combination with temozolomide. Part II of the study will be conducted in two expansion cohorts (sensitive ES-SCLC cohort and resistant ES-SCLC cohort) to further evaluate the anti-tumor activity, safety and tolerability of this regimen in ES-SCLC patients.

Being tested
IMP4297(senaparib)
Medical subject headings
Small Cell Lung Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IMP4297(senaparib)Drug

    Also called temozolomide

    The dose levels will be escalated following a modified 3+3 dose escalation scheme.

Study groups in NCT04434482
Study groupRoleWhat they receive
IMP4297(senaparib) and temozolomideExperimentalIMP4297 and temozolomide
Receives: Drug: IMP4297(senaparib)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part I: Dose Escalation safety and tolerability

    TEAEs, vital signs, physical examinations, electrocardiogram (ECG), laboratory tests (including serum chemistry, hematology, and urinalysis, coagulation), etc.

    Measured: From signing ICF until safety follow-up

  2. Part I: Dose Escalation MTD

    the maximum tolerated dose:the highest dose level at which <1/3 patients experience DLT

    Measured: from the initiation of study drugs until the end of dose escalation phase(approximately 1 year)

  3. Part I: Dose Escalation RP2D

    the recommended phase 2 dose

    Measured: from the initiation of study drugs until the end of dose escalation phase(approximately 1 year)

  4. Part II: Dose Expansion Overall Response Rate (ORR)

    the percentage of patients who had a best response rating of CR and PR which was maintained ≥4 weeks from the first manifestation of that rating.

    Measured: from the initiation of study drugs until documented disease progression, withdrawal of consent, loss to follow-up, death, initiation of new anti-cancer treatment or termination of study, which occurs first.

Secondary outcomes (7)

  1. Part I: Dose Escalation plasma PK profile of IMP4297 and temozolomide

    To characterize the plasma PK profile of IMP4297 and temozolomide via population PK (popPK) modeling

    Measured: Cycle 1 Day 1, Cycle 1 Day 15,Cycle 2 Day 1,Any cycle after cycle 2,unscheduled visit

  2. Part I: Dose Escalation anti-tumor activity

    Progression-free survival (PFS),Duration of response (DoR),Disease control rate (DCR)

    Measured: from the initiation of study drugs until documented disease progression, withdrawal of consent, loss to follow-up, death, initiation of new anti-cancer treatment or termination of study

  3. Part I: Dose Escalation,effect of IMP4297 on QT interval

    Correlation between IMP4297 plasma concentration and QT interval

    Measured: Cycle 1 Day 1,Cycle 1 Day 15,Cycle 2 Day 1,CnD1,EOT, unscheduled visit

  4. Part II: Dose Expansion safety and tolerability

    TEAE, vital signs, physical examinations, ECG, laboratory tests (including serum chemistry, hematology, urinalysis and coagulation), etc.

    Measured: From signing ICF until safety follow-up

  5. Part II: Dose Expansion anti-tumor activity

    progression-free survival (PFS ),duration of response (DoR),Disease control rate （DCR),overall survival (OS)

    Measured: from the initiation of study drugs until documented disease progression, withdrawal of consent, loss to follow-up, death, initiation of new anti-cancer treatment or termination of study

  6. Part II: Dose Expansion PK profile of IMP4297 and temozolomide

    PK parameters derived from IMP4297 and temozolomide plasma concentration data

    Measured: Cycle 1 Day 1,Cycle 1 Day 15,Cycle 2 Day 1,Any cycle after cycle 2,unscheduled visit

  7. Part II: Dose Expansion effect of IMP4297 on QT interval

    Correlation between IMP4297 plasma concentration and QT interval

    Measured: Cycle 1 Day 1,Cycle 1 Day 15,Cycle 2 Day 1,CnD1,EOT, unscheduled visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jun 2020
  2. Study start7 Aug 2020
  3. Primary completion29 Apr 2024
  4. Study completion29 Apr 2024

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04434482
Sponsor's protocol ID
IMP4297-106
Status last verified
May 2024
First submitted
14 Jun 2020
Last updated
19 Sep 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing IMP4297(senaparib) in people with Advanced Solid Tumours and Small Cell Lung Cancer, run by Impact Therapeutics, Inc. at 21 sites in 5 countries.

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 15 inclusion and 24 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: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Taiwan, United States, Australia, China, South Korea. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Part I: Dose Escalation safety and tolerability (time frame: From signing ICF until safety follow-up). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04434482.

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 19 Sep 2024.

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