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Testing GDC-0032 (Taselisib) as a Potential Targeted Treatment in Cancers With PIK3CA Genetic Changes (MATCH-Subprotocol I)

Primary Purpose

Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Taselisib
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
  • Patients must have a PIK3CA mutation as determined via the MATCH Master Protocol
  • 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 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

  • Patients must have a fasting glucose =< 125 mg/dL

    • NOTE: Please provide clear documentation that the glucose test was conducted at a fasting state
  • 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:

  • Patients must not have known hypersensitivity to GDC-0032 (taselisib) or compounds of similar chemical or biologic composition
  • Patients must not have breast cancer
  • 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
  • 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
  • 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
  • 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
  • Patients must not have type 1 or 2 diabetes requiring anti-hyperglycemic medication (e.g. metformin, glipizide, insulin)
  • Patients must not have current dyspnea at rest or require any daily supplemental oxygen
  • Patients must not have history of inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis) or active bowel inflammation (e.g. diverticulitis)

Sites / Locations

  • ECOG-ACRIN Cancer Research Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (taselisib)

Arm Description

Patients receive taselisib 4 mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR)
Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the 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. The 90% two-sided binomial exact confidence interval was calculated for ORR.

Secondary Outcome Measures

6-Month Progression-free Survival (PFS) Rate
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. The 6-month PFS rate was estimated using the Kaplan-Meier method which can provide a point estimate for any specific time point. Disease progression was evaluated using the 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.
Progression-free Survival (PFS)
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the 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.

Full Information

First Posted
June 18, 2020
Last Updated
June 6, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04439175
Brief Title
Testing GDC-0032 (Taselisib) as a Potential Targeted Treatment in Cancers With PIK3CA Genetic Changes (MATCH-Subprotocol I)
Official Title
MATCH Treatment Subprotocol I: GDC-0032 (Taselisib) in Patients With Tumors (Other Than Breast Cancer) With PIK3CA Mutation But Without KRAS Mutation or PTEN Loss
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 25, 2016 (Actual)
Primary Completion Date
November 10, 2020 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (taselisib)
Arm Type
Experimental
Arm Description
Patients receive taselisib 4 mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Taselisib
Other Intervention Name(s)
GDC-0032, RO5537381
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the 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. The 90% two-sided binomial exact confidence interval was calculated for ORR.
Time Frame
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 Outcome Measure Information:
Title
6-Month Progression-free Survival (PFS) Rate
Description
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. The 6-month PFS rate was estimated using the Kaplan-Meier method which can provide a point estimate for any specific time point. Disease progression was evaluated using the 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.
Time Frame
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, from which 6-month PFS is determined
Title
Progression-free Survival (PFS)
Description
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the 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.
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 a PIK3CA mutation as determined via the MATCH Master Protocol 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 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 Patients must have a fasting glucose =< 125 mg/dL NOTE: Please provide clear documentation that the glucose test was conducted at a fasting state 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: Patients must not have known hypersensitivity to GDC-0032 (taselisib) or compounds of similar chemical or biologic composition Patients must not have breast cancer 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 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 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 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 Patients must not have type 1 or 2 diabetes requiring anti-hyperglycemic medication (e.g. metformin, glipizide, insulin) Patients must not have current dyspnea at rest or require any daily supplemental oxygen Patients must not have history of inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis) or active bowel inflammation (e.g. diverticulitis)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ian E Krop
Organizational Affiliation
ECOG-ACRIN Cancer Research Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
ECOG-ACRIN Cancer Research Group
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19103
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Testing GDC-0032 (Taselisib) as a Potential Targeted Treatment in Cancers With PIK3CA Genetic Changes (MATCH-Subprotocol I)

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