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Gastrointestinal Stromal TumorPhase 1NCT01643278

Dasatinib and Ipilimumab in Treating Patients With Gastrointestinal Stromal Tumors or Other Sarcomas That Cannot Be Removed by Surgery or Are Metastatic

A Phase 1 study testing Dasatinib, Ipilimumab and Laboratory Biomarker Analysis in people with Gastrointestinal Stromal Tumor and Stage III Soft Tissue Sarcoma, run by National Cancer Institute (NCI) 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 phase I trial studies the side effects and best dose of dasatinib when given together with ipilimumab in treating patients with gastrointestinal stromal tumors or other sarcomas that cannot be removed by surgery or have spread to other places in the body. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Dasatinib, Ipilimumab and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteUnited States
Study dates
Jul 2012to Jun 2016
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • DOSE ESCALATION COHORT: subjects must have histologically or cytologically confirmed sarcoma that is metastatic or unresectable
  • DOSE EXPANSION COHORT: subjects must have histologically or cytologically confirmed GIST that is metastatic or unresectable
  • Patients must have measurable disease per RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • DOSE ESCALATION COHORT: patients must have had at least one prior therapy
  • DOSE EXPANSION COHORT: GIST patients must have had progression on or have been intolerant to imatinib and sunitinib
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
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  • Life expectancy of greater than 3 months
  • Leukocytes >= 3 K/mcL
  • Absolute neutrophil count >= 1.5 K/mcL
  • Platelets >= 100 K/mcL
  • Hemoglobin >= 8.0 g/dl
  • Total bilirubin =< 1.5 x institutional upper limit of normal; note: patients with hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the discretion of the treating physician and/or the principal investigator
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of dasatinib administration
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients who have had chemotherapy (non-tyrosine kinase inhibitor [TKI]) or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients with a history of prior treatment with ipilimumab or dasatinib
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases are excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to dasatinib and ipilimumab
  • Patients who require concurrent treatment with any medications or substances that are potent inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
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  • Patients who require concurrent treatment with any medications or substances that have significant proarrhythmic potential are ineligible
  • Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain dasatinib tablets are excluded
  • Patients may not have any clinically significant cardiovascular disease including the following:
  • Myocardial infarction or ventricular tachyarrhythmia within 6 months
  • Prolonged corrected QT interval (QTc) > 480 msec
  • Ejection fraction less than 50%
  • Major conduction abnormality (unless a cardiac pacemaker is present)
  • Uncontrolled intercurrent illness including, but not limited to, the following: ongoing or active infection; history of significant bleeding disorder, including congenital (von Willebrand's disease) or acquired (anti-factor VIII antibodies) disorders; large pleural effusions; or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with dasatinib
  • Subjects may not have known human immunodeficiency virus (HIV), active hepatitis A, or hepatitis B or C infection
  • Subjects with any active autoimmune disease or a documented history of autoimmune disease or history of syndrome that required systemic steroids or immunosuppressive medications including but not limited to inflammatory bowel disease, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (e.g. Guillain-Barre syndrome), and multiple sclerosis; patients with vitiligo, asthma and diabetes are NOT excluded; final determination can be left to the discretion of the principal investigator
  • Subjects may not have ongoing chronic diarrhea
  • Subjects may not have had prior organ allograft or allogeneic bone marrow transplantation
  • Subjects may not have any major surgery within 4 weeks
  • Subjects may not have known current drug or alcohol abuse
  • Subjects may not have an underlying medical condition that in the opinion of the investigator could adversely affect the ability of the subject to comply with or tolerate study procedures and/or study therapy, or confound the ability to interpret the tolerability of combined administration of dasatinib and ipilimumab in treated subjects
  • Subjects may not have other active malignancies other than indolent malignancies not requiring active therapy which the investigator determines are unlikely to interfere with treatment and safety analysis

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: Phase I Study of Dasatinib in Combination With Ipilimumab for Patients With Advanced Gastrointestinal Stromal Tumor and Other Sarcomas

This phase I trial studies the side effects and best dose of dasatinib when given together with ipilimumab in treating patients with gastrointestinal stromal tumors or other sarcomas that cannot be removed by surgery or have spread to other places in the body. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways by targeting certain cells. Giving dasatinib together with ipilimumab may be a better treatment for patients with gastrointestinal stromal tumors or other sarcomas.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety and tolerability of treatment with ipilimumab in combination with dasatinib in subjects with gastrointestinal stromal tumor (GIST) and other advanced sarcomas.

SECONDARY OBJECTIVES:

  1. Response rate (RR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, immune-related response criteria, and Choi criteria.

II. Progression free survival (PFS). III. Progression-free survival at 6 months (PFS6months). IV. Overall survival (OS). V. Immunological correlative studies.

OUTLINE: This is a dose-escalation study of dasatinib.

Patients receive dasatinib orally (PO) once daily (QD) for 7 days. Patients then receive dasatinib PO QD and ipilimumab intravenously (IV) once on weeks 1, 4, 7 and 10. Beginning on week 24, patients then receive dasatinib PO QD and ipilimumab IV once every 12 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 3 months.

Being tested
Dasatinib, Ipilimumab, Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings
Gastrointestinal Stromal Tumors, Sarcoma

What participants receive

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

  • DasatinibDrug

    Also called BMS-354825, Sprycel

    Given PO

  • 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

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT01643278
Study groupRoleWhat they receive
Treatment (dasatinib and ipilimumab)ExperimentalPatients receive dasatinib PO QD for 7 days. Patients then receive dasatinib PO QD and ipilimumab IV once on weeks 1, 4, 7 and 10. Beginning on week 24, patients then receive dasatinib PO QD and ipilimumab IV once every 12 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Dasatinib; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

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

  1. Maximum tolerated dose defined as the highest dose studied for which the observed incidence of dose-limiting toxicity is less than 33% according to the National Cancer Institute Common Toxicity Criteria

    Frequencies of toxicities will be tabulated.

    Measured: Up to week 12

Secondary outcomes (4)

  1. OS as measured by RECIST 1.1, Choi and immune-related response criteria

    Will be estimated using Kaplan-Meier methodology.

    Measured: Up to 3 years

  2. PFS as measured by RECIST 1.1, Choi and immune-related response criteria

    Will be estimated using Kaplan-Meier methodology.

    Measured: From start of treatment to time of progression or death, whichever occurs first, assessed up to 3 years

  3. PFS at 6 months as measured by RECIST 1.1, Choi and immune-related response criteria

    Will be estimated using Kaplan-Meier methodology.

    Measured: 6 months

  4. RR as measured by RECIST 1.1, Choi and immune-related response criteria

    Immune related response rate (complete response + partial response) and Choi criteria will be calculated along with a 95% confidence interval.

    Measured: Up to 3 years

Timeline

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

  1. First posted18 Jul 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionJun 2016
  4. Study completionJun 2016

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01643278
Sponsor's protocol ID
NCI-2012-01165
Other IDs
NCI-2012-01165, CDR0000737378, 12-083, 9172, 9172, P30CA008748, U01CA069856
Status last verified
Jan 2017
First submitted
16 Jul 2012
Last updated
10 Jan 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dasatinib, Ipilimumab and Laboratory Biomarker Analysis in people with Gastrointestinal Stromal Tumor and Stage III Soft Tissue Sarcoma, run by National Cancer Institute (NCI) 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 16 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: finished, as of the sponsor's last update on 10 Jan 2017. 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 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 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?

Maximum tolerated dose defined as the highest dose studied for which the observed incidence of dose-limiting toxicity is less than 33% according to the National Cancer Institute Common Toxicity Criteria (time frame: Up to week 12). 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 NCT01643278.

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 10 Jan 2017.

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