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MelanomaPhase 1/2NCT04546074

Imatinib Mesylate in Combination With Pembrolizumab in Patients With Melanoma

A Phase 1/2 study testing Pembrolizumab and Imatinib mesylate in people with Melanoma, run by Keio University at 1 site in Japan.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is an open-labelled single arm trial of pembrolizumab and imatinib mesylate in subjects with unresectable or metastatic KIT-mutant melanoma that are refractory to standard therapy. The phase Ib and II study will be conducted to evaluate the safety, tolerability and response rate data of this combination therapy. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Melanoma
What is being tested?
Pembrolizumab and Imatinib mesylate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteJapan
Study dates
14 Sep 2020to 31 Oct 2025
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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1. Be male or female subjects, age 20 years or older on day of signing consent.
  • 2. Have histologically confirmed melanoma.
  • 3. Have unresectable or metastatic melanoma with KIT mutations detected by next-generation sequencing which was performed at clinical laboratories accredited by international standards such as CLIA and CAP certification.
  • 4. Have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
  • Received at least 2 doses of an approved anti-PD-1/L1 mAb.
  • Has demonstrated disease progression after PD-1/L1 as defined by RECIST 1.1. The initial evidence of disease progression is to be confirmed by second assessment no less than 4 weeks from the date of the first documented progressive disease, in the absence of rapid clinical progression. This determination is made by the investigator. Once progressive disease is confirmed, the initial date of progressive disease documentation will be considered the date of disease progression.
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  • Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb or during the treatment. In adjuvant therapy, progressive disease has been documented within 6 months from the last dose of anti-PD-1/L1 mAb or during the treatment.
  • 5. Have no prior treatment with KIT inhibitors.
  • 6. Have completed previous therapies 21 days prior to enrollment on study.
  • 7. Have the presence of at least one measurable lesion by CT or MRI per RECIST 1.1 criteria as determined by the local site investigator/radiology assessment within 14-days prior to enrollment on study.
  • 8. Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
  • 9. Have life expectancy of greater than 90 days.
  • 10. Have known no active central nervous system (CNS) metastases. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 28 days before enrollment on study and any neurologic symptoms).
  • 11. If female of childbearing potential, must be willing to use an adequate method of contraception and agree not to breastfeed for the course of the study through 120 days after the last dose of study medication. If male of childbearing potential, must agree to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.
  • 12. Have laboratory parameters within Protocol-defined range. The screening laboratory tests below must be ≤14 days before enrollment on study.
  • <!-- -->
  • White blood cell count ≥ 2,000/mm^3 and absolute neutrophil count ≥1,500/mm^3.
  • Platelets ≥ 100,000/mm^3.
  • Hemoglobin ≥ 9 g/dL.
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 150 IU/L.
  • Bilirubin ≤ 2.0 mg/dl.
  • Serum creatinine ≤ 1.5 mg/dl. 13. Be willing and able to review, understand and provide written consent before starting therapy.

Who cannot join

  • 1. Be seropositive for hepatitis B antigen, or hepatitis C antibody. Even if negative for HBs antigen, subjects who are positive for HBs antibody or HBc antibody and amount of HBV-DNA exceed detection sensitivity are excluded from the study.
  • 2. Has known history of human immunodeficiency virus（HIV) (HIV 1/2 antibodies).
  • 3. Has a history of (no-infectious) pneumonitis that required steroids.
  • 4. Has ongoing or active infections, symptomatic heart failure, unstable angina pectoris, cardiac arrhythmias, interstitial pneumonia, pneumonitis, or psychiatric disorders that would interfere with cooperation with the requirements of the study.
  • 5. Has known superior vena cava syndrome, pericardial effusion, pleural effusion, or ascites of grade 3 or higher.
  • 6. Has presence of a gastrointestinal condition that may affect drug absorption.
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  • 7. Receiving or necessary to continue administering CYP3A4 inhibitors or drugs metabolized by CYP3A4.
  • 8. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include cancers that have not recurred for at least 3 years before enrollment on study and early stage cancers (carcinoma in situ or stage 1) treated with curative intent, basal cell carcinoma of the skin, or superficial bladder cancer that has undergone potentially curative therapy.
  • 9. Has an active autoimmune disease that has required systemic treatment in past 2 years.
  • 10. Has history of organ transplantation including hematopoietic stem cell transplantation.
  • 11. Receiving chronic systemic steroid therapy. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • 12. Pregnant women and breastfeeding woman.
  • 13. Has received live vaccine within 30 days before the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
  • 14. 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.

Trial locations and contacts

1 site in 1 country.

Takeru Funakoshi, MD contact

+81-3-5363-3823

takeruf@keio.jp

Japan1 site, 1 recruiting

  • Keio University Hospital

    Shinjuku, Tokyo, 1608582

    Takeru Funakoshi, MD, +81-3-5363-3823, takeruf@a8.keio.jp

    Recruiting

Other trials in Japan

About this study

Official title: Imatinib Mesylate in Combination With Pembrolizumab in Patients With Advanced KIT-mutant Melanoma Following Progression on Standard Therapy: a Phase I/II Trial

This is an open-labelled single arm trial of pembrolizumab and imatinib mesylate in subjects with unresectable or metastatic KIT-mutant melanoma that are refractory to standard therapy. The phase Ib and II study will be conducted to evaluate the safety, tolerability and response rate data of this combination therapy. KIT-mutant tumors will be confirmed in previously biopsied tumors. This analysis will be done by next-generation sequencing.

Read the detailed description

This trial is conducted as "Advanced medicine" authorized by the Ministry of Health, Labor, and Welfare (MHLW) in Japan, and in in conformance with Clinical Trial Act.

PIb study is a dose-escalation study comprising two dose levels of imatinib mesylate with fixed dose of pembrolizumab to evaluate safety and tolerability and identify maximum tolerated dose/administered, and determine recommended phase 2 dose (RP2D).

In PII study, a Simon's minimax two-stage design is employed.The treatment period with the combination therapy of both studies will continue every 21 days for up to 33 cycles (approximately 2 years) as long as subjects are receiving benefit from treatment and have not had disease progression or met any criteria for study withdrawal.

Conditions
Melanoma
Being tested
Pembrolizumab and Imatinib mesylate
Keywords
KIT
Medical subject headings
Melanoma

What participants receive

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

  • Pembrolizumab and Imatinib mesylateDrug

    In Phase Ib study:

    Level 1: Imatinib mesylate 200mg QD + Pembrolizumab 200mg Q3W, Level 2: Imatinib mesylate 400mg QD + Pembrolizumab 200mg Q3W

  • Pembrolizumab and Imatinib mesylateDrug

    In Phase II study, eligible patients receive the dose determined in phase Ib cohort.

Study groups in NCT04546074
Study groupRoleWhat they receive
TreatmentExperimentalNot described
Receives: Drug: Pembrolizumab and Imatinib mesylate

What is being measured

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

  1. Objective in phase Ib study

    Dose Limiting Toxicities (DLT) rates of pembrolizumab and imatinib mesylate combination therapy

    Measured: at 6 weeks

  2. Objective in phase II study

    Objective response rate (ORR) of treatment with recommended dose of imatinib mesylate with fixed dose of pembrolizumab according to RECIST version 1.1.

    Measured: at 12 weeks

Secondary outcomes (4)

  1. Progression-free survival (PFS)

    Measured: From date of registration until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 60 months.

  2. Overall survival (OS)

    Measured: From date of registration until the date of to death from any cause, assessed up to 60 months.

  3. Best overall response (BOR)

    BOR is defined from the overall efficacy determined by the end of this trial according to RECIST 1.1

    Measured: From date of initiation of treatment until the date of the end of treatment. The maximum period for treatment is 2 years.

  4. Incidence of adverse events (AEs) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: Be followed up to 30 days after the cessation of treatment

Timeline

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

  1. First posted11 Sep 2020
  2. Study start14 Sep 2020
  3. Primary completion31 Oct 2024 (estimated)
  4. Study completion31 Oct 2025 (estimated)

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
22 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04546074
Sponsor's protocol ID
N20190002
Status last verified
Oct 2023
First submitted
29 Aug 2020
Last updated
3 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hirai I, Tanese K, Fukuda K, Fusumae T, Nakamura Y, Sato Y, Amagai M, Funakoshi T. Imatinib mesylate in combination with pembrolizumab in patients with advanced KIT-mutant melanoma following progression on standard therapy: A phase I/II trial and study protocol. Medicine (Baltimore). 2021 Dec 10;100(49):e27832. doi: 10.1097/MD.0000000000027832.

    PubMed 34889232

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pembrolizumab and Imatinib mesylate in people with Melanoma, run by Keio University at 1 site in Japan.

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 22 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 3 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Takeru Funakoshi, MD (+81-3-5363-3823, takeruf@keio.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective in phase Ib study (time frame: at 6 weeks). The study lists 2 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 NCT04546074, which also lists 1 linked publication.

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 3 Oct 2023.

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