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

NCT01643278 | Completed Phase 1 DMC

• 6 other identifiers: NCI-2012-01165CDR000073737812-0839172P30CA008748U01CA069856
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Gastrointestinal Stromal Tumor; Stage III Soft Tissue Sarcoma; Stage IV Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (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.

  Up to week 12

Secondary Outcomes (4)

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

  Up to 3 years

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

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

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

  6 months

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

  Up to 3 years

Other Outcomes (4)

• Change in humoral and cellular immune response

  Baseline to up to 4 weeks after treatment

• Change in tumor immunological markers in patients treated at the expansion cohort (as of May 2015 patients on expansion cohort will not undergo protocol biopsies)

  Baseline to up to week 6

• Downstream molecular effects of therapy on tumor viability as measured by changes in KIT expression and secondary mutations in resistant tumor specimens

  Baseline to up to 4 weeks after treatment

Study Arms (1)

Treatment (dasatinib and ipilimumab)

EXPERIMENTAL

Patients 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.

Drug: Dasatinib; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Dasatinib DRUG

Given PO

Also known as: BMS-354825, Sprycel

Treatment (dasatinib and ipilimumab)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Treatment (dasatinib and ipilimumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (dasatinib and ipilimumab)

Pharmacological Study OTHER

Correlative studies

Treatment (dasatinib and ipilimumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%)
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Sarcoma

Interventions

Dasatinib; Ipilimumab; CTLA-4 Antigen

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Sandra D'Angelo

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2012
• First Posted: July 18, 2012
• Study Start: July 1, 2012
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: January 10, 2017

Record last verified: 2017-01

Locations

US (1)