Testing GDC-0032 (Taselisib) as a Potential Targeted Treatment in Cancers With PIK3CA Genetic Changes (MATCH-Subprotocol I)
Study Details
Study Description
Brief Summary
This phase II MATCH treatment trial identifies the effects of GDC-0032 (taselisib) in patients whose cancer has a genetic change called PIK3CA mutation. Taselisib may stop the growth of cancer cells by blocking PIK3CA, a protein that may be needed for cell growth. Researchers hope to learn if taselisib will shrink this type of cancer or stop its growth.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
PRIMARY OBJECTIVE:
- 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:
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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.
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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.
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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 taselisib 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (taselisib) Patients receive taselisib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Drug: Taselisib
Given PO
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Objective response rate (ORR) [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]
ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.
Secondary Outcome Measures
- Overall survival (OS) [Assessed every 3 months for =< 2 years and every 6 months for year 3]
OS is defined as time from treatment start date to date of death from any cause. Patients alive at the time of analysis are censored at last contact date. OS will be evaluated specifically for each drug (or step) using the Kaplan-Meier method.
- Progression free survival (PFS) [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]
PFS is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
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Patients must have a PIK3CA mutation as determined via the MATCH Master Protocol
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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)
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Patients with known left ventricular dysfunction must have echocardiogram (ECHO) or multigated acquisition scan (MUGA) 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
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Patients must have a fasting glucose =< 125 mg/dL
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NOTE: Please provide clear documentation that the glucose test was conducted at a fasting state
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Patients with prior treatment with an mTOR inhibitor are acceptable. These include, but are not limited to: temsirolimus, everolimus, ridaforolimus, sirolimus, CC-223, MLN128 (INK128), DS-3078, CC-115, AZD-2014, AZD8055
Exclusion Criteria:
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Patients must not have known hypersensitivity to GDC-0032 (taselisib) or compounds of similar chemical or biologic composition
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Patients must not have breast cancer
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Patients with squamous cell carcinoma of the lung who have PIK3CA mutations who have access to AND are eligible for Lung-MAP (S1400) are not eligible
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Patients must not have KRAS mutations, and/or PTEN mutation or loss, detected in the tumor sample as determined by the MATCH screening assessment. PTEN loss will be determined by immunohistochemistry
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Patients must not have had prior therapy with a PI3K inhibitor or PI3K/mTOR inhibitor. These include, but are not limited to: BEZ235, XL-765 (SAR245409), GDC-0980, PF-04691502, PF-05212384 (PKI-587), SF-1126, GSK 2126458, P-7170, BGT-226, LY3023414, GDC-0084, DS-7423, BKM-120 (buparlisib), PX-866, XL-147, GDC-0941 (pictilisib), VS-5584, BAY-80-6946, ZSTK-474, WX 037, AZD8835, GSK2636771, GS-9820, BYL719, MLN1117 (INK1117), idelalisib, TGR1202, RP6530, duvelisib (IPI-145), CUDC-907. Prior GDC-0032 (taselisib) is not allowed
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Patients must not have had prior therapy with an Akt inhibitor. These include, but are not limited to: MK-2206, GSK690693, AZD5363, triciribine, perifosine, GSK2141795, GSK2110183, SR13668, BAY1125976, GDC-0068 (ipatasertib), LY2780301, ARQ092
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Patients must not have type 1 or 2 diabetes requiring anti-hyperglycemic medication (e.g. metformin, glipizide, insulin)
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Patients must not have current dyspnea at rest or require any daily supplemental oxygen
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Patients must not have history of inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis) or active bowel inflammation (e.g. diverticulitis)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ECOG-ACRIN Cancer Research Group | Philadelphia | Pennsylvania | United States | 19103 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Ian E Krop, ECOG-ACRIN Cancer Research Group
Study Documents (Full-Text)
More Information
Publications
None provided.- NCI-2020-03142
- NCI-2020-03142
- EAY131-I
- EAY131-I
- U10CA180820
- U24CA196172