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Gastrointestinal Stromal TumorPhase 2NCT02880020

Nivolumab With or Without Ipilimumab in Treating Patients With Gastrointestinal Stromal Tumor That Is Metastatic or Cannot Be Removed by Surgery

A Phase 2 study testing Ipilimumab, Laboratory Biomarker Analysis and Nivolumab in people with Gastrointestinal Stromal Tumor, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

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 randomized phase II trial studies how well nivolumab with or without ipilimumab works in treating patients with gastrointestinal stromal tumor that has spread to other places in the body or cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gastrointestinal Stromal Tumor
What is being tested?
Ipilimumab, Laboratory Biomarker Analysis and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteUnited States
Study dates
14 Dec 2016to 9 Aug 2022
Phase
Phase 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

  • Written informed consent must be obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
  • Life expectancy > 12 weeks
  • Histological confirmation of GIST
  • Mutational testing of patient samples for KIT and platelet-derived growth factor receptor (PDGFR) mutations; (this will not hold up starting therapy, but will be done for all patients lacking up front mutational testing)
  • Patients must have refused or have evidence of intolerance to or progression on imatinib
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  • This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (i.e., subject has not been randomized / has not been treated); if re-enrolled, the subject must be re-consented
  • Adequate archival tissue must be available from the prior 3 months to signing consent; if not, an adequate tumor specimen obtained by either excisional biopsy, incisional biopsy or core needle biopsy must be sent to the central pathology lab for evaluation; the material must measure at least 0.8 × 0.1 cm in size or contain at least 100 tumor cells
  • Measurable tumor lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Hemoglobin >= 9 g/dL
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 × institutional upper limit of normal (ULN); for subjects with liver metastases, AST or ALT =< 5 × ULN
  • Bilirubin =< 1.5 × ULN; for subjects with documented/suspected Gilbert's disease, bilirubin =< 3 × ULN
  • Willingness to provide consent for biopsy samples; tumor biopsies will be required for all subjects, tumor lesions used for biopsy should not be lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy; if a RECIST target lesion is used for biopsy the lesion must be >= 2 cm in longest diameter
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of study drug
  • Women must not be breastfeeding
  • Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug (25 days) plus 30 days (duration of ovulatory cycle) for a total of 155 days post-treatment completion
  • Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of the study drug plus 90 days (duration of sperm turnover) for a total of 215 days post-treatment completion; in addition, male subjects must be willing to refrain from sperm donation during this time
  • Azoospermic males are exempt from contraceptive requirements; WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section
  • Male subjects must be willing to refrain from sperm donation during the entire study and for 5 half-lives of study drug plus 90 days (duration of sperm turnover) after dosing has been completed
  • At a minimum, subjects must agree to use one highly effective (which have a failure rate of < 1% when used consistently and correctly) OR one less effective method of contraception as listed below:
  • WOCBP and female partners of male subjects, who are WOCBP, are expected to use one of the highly effective methods of contraception listed below; male subjects must inform their female partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner; contraception methods are as follows:
  • Progestogen only hormonal contraception associated with inhibition of ovulation
  • Hormonal methods of contraception including oral contraceptive pills containing combined estrogen + progesterone, vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena
  • Nonhormonal IUDs, such as ParaGard
  • Bilateral tubal occlusion
  • Vasectomised partner with documented azoospermia 90 days after procedure
  • Intrauterine hormone-releasing system (IUS)
  • Complete abstinence
  • Less effective methods of contraception
  • Diaphragm with spermicide
  • Cervical cap with spermicide
  • Vaginal sponge with spermicide
  • Male or female condom with or without spermicide
  • Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
  • Unacceptable methods of contraception
  • Periodic abstinence (calendar, symptothermal, post-ovulation methods)
  • Withdrawal (coitus interruptus)
  • Spermicide only
  • Lactation amenorrhea method (LAM)

Who cannot join

  • Palliative surgery and/or radiation treatment within 28 days prior to course 1 day 1 (C1D1)
  • Localized therapy of non-target lesions is allowed
  • No steroids are permitted within 28 days of C1D1; or doses < 10mg/day prednisone equivalent or levels necessary for physiologic replacement
  • Women who are of pregnant or breastfeeding
  • Inability to give informed consent
  • An inadequate tumor specimen as defined by the local pathologist
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  • History of other malignancies except cured basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma in situ, superficial bladder cancer or carcinoma in situ of the cervix; for other malignancies, must be documented to be free of cancer for >= 2 years; all other cases can be considered on a case by case basis at the discretion of the principal investigator
  • Any condition that might interfere with the subject's participation in the study, safety, or in the evaluation of the study results
  • Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
  • Prior exposure to any anti-PD-1 or anti-PD-L1 antibody, or any anti-cytotoxic T-lymphocyte-associated protein (CTLA) 4 antibodies
  • Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment; concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of nivolumab, with the exceptions of intranasal, topical, and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent (use for brain metastases is not permitted 28 days prior to start of therapy)
  • Active or prior documented autoimmune disease within the past 3 years
  • NOTE: subjects with active, known or suspected autoimmune disease such as vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • History of organ transplant that requires use of immunosuppressives
  • Active or prior documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis) or a history of primary immunodeficiency
  • Exposure to any therapeutic agent (investigational or conventional) within 7 days of date of randomization or to any agent for which 5 half lives have not elapsed
  • Unresolved toxicities from prior anticancer therapy, defined as having not resolved to National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE) (NCI CTCAE version [v]4.03) grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia; subjects with irreversible toxicity that is not reasonably expected to be exacerbated by nivolumab may be included (eg, hearing loss) after consultation with the principal investigator
  • Subjects who active hepatitis B or C, or human immunodeficiency virus (HIV)
  • Prisoners or subjects who are involuntarily incarcerated; (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Rachel Andes

    Los Angeles, California, 90095

Other trials in United States

About this study

Official title: A Randomized Phase 2 Study of Nivolumab Monotherapy Versus Nivolumab Combined With Ipilimumab in Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor (GIST)

This randomized phase II trial studies how well nivolumab with or without ipilimumab works in treating patients with gastrointestinal stromal tumor that has spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as nivolumab and ipilimumab, interfere with the ability of tumor cells to grow and spread.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the response rate of nivolumab alone and in combination with ipilimumab in subjects with metastatic or locally advanced/unresectable gastrointestinal stromal tumor (GIST).

SECONDARY OBJECTIVES:

  1. Ascertain the response rate of nivolumab alone and in combination of ipilimumab in subjects with metastatic or locally advanced/unresectable GIST by Choi criteria.

II. Assess the progression-free survival (PFS). III. Ascertain the clinical benefit rate (CBR = complete response [CR] + partial response [PR] and stable disease [SD]) of nivolumab and ipilimumab in refractory/unresectable GIST.

IV. Explore the safety of nivolumab monotherapy and nivolumab and ipilimumab in this population assessed by the frequency and severity of adverse events (AEs).

TERTIARY OBJECTIVES:

  1. Compare RR and CBR in patients whose tumors are programmed cell death ligand 1 (PD-L1) positive (+) and PD-L1 negative (-) at baseline.

II. In the patients who are PD-L1 positive, compare RR and CBR in patients with 1% and 5% tumor membrane staining.

III. Determine the baseline mutational load of patients at the start of treatment.

IV. Determine the response to treatment based on the baseline mutation load and baseline GIST mutations.

  1. Determine the response rate based on GIST mutational status.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive nivolumab intravenously (IV) over 60 minutes on day 1. Courses repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes every 6 weeks. Courses repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Being tested
Ipilimumab, Laboratory Biomarker Analysis, Nivolumab
Medical subject headings
Gastrointestinal Stromal Tumors

What participants receive

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

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

Study groups in NCT02880020
Study groupRoleWhat they receive
Arm I (nivolumab)ExperimentalPatients receive nivolumab IV over 60 minutes on day 1. Courses repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Biological: Nivolumab
Arm II (nivolumab, ipilimumab)ExperimentalPatients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes every 6 weeks. Courses repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab

What is being measured

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

  1. Overall response rate defined as the number of subjects with a best objective response of confirmed CR or PR divided by the number of subjects

    Will utilize an exact binomial test to compare the RECIST response rate separately within each of the two study arms. Additionally, an exact 95% confidence interval will be constructed within each arm.

    Measured: Up to 2 years

Secondary outcomes (4)

  1. Clinical benefit rate

    The endpoint will utilize an exact binomial test to compare the RECIST response rate separately within each of the two study arms. Additionally, an exact 95% confidence interval will be constructed within each arm.

    Measured: Up to 2 years

  2. Frequency and severity of AEs assessed by NCI CTCAE v 4.03

    Will be tabulated by type, severity, and the proportion of subject experiencing the event. Fisher's exact tests will be used to compare the AE rates between groups for each category of AE and compute exact 95% confidence intervals for the rates of AEs.

    Measured: Up to 2 years

  3. Progression free survival time

    Time to disease progression will be plotted using Kaplan-Meier curves and compared between groups with log-rank tests.

    Measured: Up to 2 years

  4. Response rate by Choi criteria

    Will utilize an exact binomial test to compare the response rate separately within each of the two study arms. Additionally, an exact 95% confidence interval will be constructed within each arm.

    Measured: Up to 2 years

Timeline

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

  1. First posted26 Aug 2016 (estimated)
  2. Study start14 Dec 2016
  3. Primary completion9 Aug 2022
  4. Study completion9 Aug 2022

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02880020
Sponsor's protocol ID
16-000525
Other IDs
NCI-2016-01004
Status last verified
Oct 2021
First submitted
23 Aug 2016
Last updated
18 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ipilimumab, Laboratory Biomarker Analysis and Nivolumab in people with Gastrointestinal Stromal Tumor, run by Jonsson Comprehensive Cancer Center at 1 site 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 41 inclusion and 21 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 18 Aug 2022. 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 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 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?

Overall response rate defined as the number of subjects with a best objective response of confirmed CR or PR divided by the number of subjects (time frame: Up to 2 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 NCT02880020.

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 Aug 2022.

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