AzTrials
AzTrials

Stage IIIA Skin MelanomaPhase 1/2NCT02812693

Pembrolizumab and Imatinib in Patients With Locally Advanced/Metastatic Melanoma With c-KIT Mutation/Amplification

A Phase 1/2 study testing Imatinib Mesylate, Laboratory Biomarker Analysis and Pembrolizumab in people with Stage IIIA Skin Melanoma and Stage IIIB Skin Melanoma, run by Joanne Jeter.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

This phase I/II trial studies the side effects and how well pembrolizumab and imatinib mesylate work in treating patients with melanoma with c-KIT mutation or amplification that has spread to nearby tissue or other places in the body. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Imatinib Mesylate, Laboratory Biomarker Analysis and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
4 Nov 2016to 20 Nov 2017
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

  • Patient must have histologically or cytologically confirmed diagnosis of stage III melanoma inoperable/not amenable to local treatment or stage IV melanoma.
  • Patient must have either mutation or amplification of c-KIT gene tested by commercially available molecular or gene sequencing techniques
  • Be willing and able to provide written informed consent/assent for the trial
  • Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the sponsor
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
Show all 18Show fewer
  • Absolute neutrophil count (ANC) >= 1,500 /mcL
  • Platelets >= 100,000 / mcL
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
  • Serum creatinine =< 1.5 X upper limit of normal (ULN) or measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
  • Serum total bilirubin =< 1.5 X ULN or direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases
  • Albumin >= 2.5 mg/dL
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated Partial Thromboplastin Time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Female subject of childbearing potential must have a negative urine or serum pregnancy 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 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

Who cannot join

  • 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 is receiving immunosuppressive therapy within 7 days prior to the first dose of trial treatment; individuals who are receiving systemic steroid therapy at a stable dose less than or equal to 10mg of prednisone per day or its equivalent will be permitted to participate
  • Has a known history of active TB (bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab, imatinib, or any of its excipients
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
Show all 23Show fewer
  • Note: subjects with =< grade 2 neuropathy and/or alopecia are an exception to this criterion and may qualify for the study
  • Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids at a dose exceeding 10mg of prednisone per day or its equivalent for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids exceeding 10 mg prednisone per day or its equivalent, or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has known history of, or any evidence of, active, non-infectious 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 trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has decompensated congestive heart failure as defined by New York Heart Association (NYHA) functional classification III or IV
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, or anti-PD-L2 agent
  • Has received prior therapy with imatinib or another tyrosine kinase inhibitor
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days of planned start of study therapy
  • Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

About this study

Official title: A Phase 1/2 Trial of Pembrolizumab in Combination With Imatinib in Patients With Locally Advanced or Metastatic Melanoma With c-KIT Mutation or Amplification

This phase I/II trial studies the side effects and how well pembrolizumab and imatinib mesylate work in treating patients with melanoma with c-KIT mutation or amplification that has spread to nearby tissue or other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and imatinib mesylate may work better in treating patients with melanoma with c-KIT mutation or amplification that has spread to nearby tissue or other places in the body.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the best overall response rate (BORR = complete response + partial response) of the combination of pembrolizumab and imatinib for treatment of melanomas harboring c-Kit mutation or amplification.

II. To evaluate the safety and adverse effect profile of the combination of pembrolizumab and imatinib in patients with melanomas harboring c-KIT aberrations (mutations or amplifications).

SECONDARY OBJECTIVES:

  1. To assess the median time to progression (TTP), progression free survival (PFS), and overall survival (OS).

TERTIARY OBJECTIVES:

  1. Assessment of programmed cell death ligand (PD-L)1 expression in melanoma patients with c-KIT aberrations before and after combined therapy.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and imatinib mesylate orally (PO) once daily (QD) on days 1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 9 weeks for 1 year, and then every 12 weeks thereafter.

Being tested
Imatinib Mesylate, Laboratory Biomarker Analysis, Pembrolizumab
Medical subject headings
Melanoma

What participants receive

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

  • Imatinib MesylateDrug

    Also called CGP 57148, CGP57148B, Gleevec, Glivec

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT02812693
Study groupRoleWhat they receive
Treatment (pembrolizumab, imatinib)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1 and imatinib mesylate orally PO QD on days 1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Imatinib Mesylate; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

What is being measured

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

  1. BORR

    Will be estimated with a 95% exact confidence interval.

    Measured: Up to 4 years

Secondary outcomes (5)

  1. Change in PD-1 and PDL-1 expression levels

    Will be performed by estimating the 95% confidence interval for the difference in PD-1 and PDL-1 expression levels, respectively. Descriptive statistics and graphical displays will be used to evaluate change in biologic markers between pre- and post-treatment. A paired t-test will be used to determine if there is a statistically significant change.

    Measured: Baseline to 4 years

  2. Incidence of adverse events assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    Will be assessed by computing the proportion of patients with adverse events, along with an exact 95% confidence interval.

    Measured: Up to 4 years

  3. OS

    The distribution will be assessed using the Kaplan Meier method.

    Measured: From registration until death from any cause, assessed up to 4 years

  4. PFS

    Distribution of PFS time will be estimated using the method of Kaplan Meier.

    Measured: From registration until disease progression or death, assessed up to 4 years

  5. TTP

    Will be estimated using a Kaplan-Meier method.

    Measured: From registration until disease progression or death, assessed up to 4 years

Timeline

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

  1. First posted24 Jun 2016 (estimated)
  2. Study start4 Nov 2016
  3. Primary completion20 Nov 2017
  4. Study completion20 Nov 2017

Why it stopped: poor accrual

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02812693
Sponsor's protocol ID
OSU-15280
Other IDs
NCI-2016-00864, P30CA016058
Status last verified
Apr 2018
First submitted
22 Jun 2016
Last updated
5 Apr 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Imatinib Mesylate, Laboratory Biomarker Analysis and Pembrolizumab in people with Stage IIIA Skin Melanoma and Stage IIIB Skin Melanoma, run by Joanne Jeter.

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 18 inclusion and 23 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 5 Apr 2018. 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 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 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?

BORR (time frame: Up to 4 years). 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 NCT02812693.

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 5 Apr 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in