Clinical trial NCT04439305: Testing Dasatinib as a Potential Targeted Treatment in Cancers With DDR2 Genetic Changes (MATCH-Subprotocol X)
Official title: MATCH Treatment Subprotocol X: Phase II Study of Dasatinib in Patients With Tumors With DDR2 Mutations
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Advanced Lymphoma
Advanced Malignant Solid Neoplasm
Hematopoietic and Lymphoid Cell Neoplasm
Refractory Lymphoma
Refractory Malignant Solid Neoplasm
Refractory Plasma Cell Myeloma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2020-06-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II MATCH treatment trial identifies the effects of dasatinib in patients whose cancer has a genetic change called DDR2 mutation. Dasatinib may block proteins called tyrosine kinases, which may be needed for cancer cell growth. Researchers hope to learn if dasatinib will shrink this type of cancer or stop its growth.

Detailed description: PRIMARY OBJECTIVE:

I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

Patients receive dasatinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Eligibility criteria: Inclusion Criteria:

* Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
* Patients must have one of the following missense mutations in DDR2: S768R, I638F, L239R
* Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
* Patients with known left ventricular dysfunction must have an echocardiogram (ECHO) or a nuclear study (multigated acquisition scan \[MUGA\] or First Pass) within 4 weeks prior to registration to treatment and must not have left ventricular ejection fraction (LVEF) \< institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be \> 50% for the patient to be eligible

Exclusion Criteria:

* Patients must not have known hypersensitivity to dasatinib or compounds of similar chemical or biologic composition
* Patients with prior use of dasatinib will be excluded
* Dasatinib should NOT be given in the presence of STRONG CYP 3A4 inhibitors/inducers. Patients who take these drugs concurrently are ineligible for treatment with dasatinib. These drugs must be discontinued prior to initiation of dasatinib
* Dasatinib should NOT be given in the presence of H2-antagonists or proton pump inhibitors. Patients who take these drugs concurrently are ineligible for treatment with dasatinib. These drugs must be discontinued prior to initiation of dasatinib. Antacids taken 2 hours before or after dasatinib administration can be used in place of H2-antagonists or proton pump inhibitors if some acid-reducing therapy is needed

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Assessed every 3 months for =< 2 years and every 6 months for year 3
measure: Progression free survival (PFS)
timeFrame: Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: ECOG-ACRIN Cancer Research Group
state: Pennsylvania
Study officials:
affiliation: ECOG-ACRIN Cancer Research Group
name: Mary D Chamberlin
role: PRINCIPAL_INVESTIGATOR
References: