- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05490771
Testing Copanlisib as a Potential Targeted Treatment in Cancers With PIK3CA Mutations (MATCH-Subprotocol Z1F)
Phase II Study of Copanlisib in Patients With Tumors With PIK3CA Mutations (PTEN Loss Allowed)
Study Overview
Status
Conditions
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 copanlisib intravenously (IV) over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsies at screening and end of treatment and computed tomography (CT) or magnetic resonance imaging (MRI) at baseline, every 2 cycles for the first 26 cycles, and then every 3 cycles thereafter until progressive disease or start of another MATCH treatment step.
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Pennsylvania
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Philadelphia, Pennsylvania, United States, 19103
- ECOG-ACRIN Cancer Research Group
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
- Patients must have 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 should stop using herbal medications at least 7 days prior to the first dose of copanlisib. Herbal medications include, but are not limited to: St. John's Wort, Kava, ephedra, gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, black cohosh and ginseng
- Patients with type I or II diabetes mellitus must have glycosylated hemoglobin A1c (HbA1c) =< 8.5% within 28 days from registration
- Absolute neutrophil count (ANC) >= 1.5 x 10^9 /L
- Platelets >= 100x10^9/L
- Hemoglobin (Hb) > 9 g/dl
- Total serum bilirubin < 2.0 mg/dL
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN) (< 5 x ULN in patients with liver metastases)
- Serum creatinine < 1.5 x ULN
- Men and women of child-bearing potential must agree to use contraception while receiving study treatment and for 1 month after the last dose of copanlisib
Exclusion Criteria:
- Patients must not have known hypersensitivity to copanlisib or compounds of similar chemical or biologic composition
- Patients must not have had prior therapy with copanlisib or other PI3K inhibitors, AKT inhibitors or mTOR inhibitors
- Patients must not have activating KRAS mutations
- Patients must not have HER2 positive (3+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH] ratio >= 2) breast cancer
- Patients must not have indolent non-Hodgkin lymphoma (NHL) (follicular lymphoma, small lymphocytic lymphoma [SLL]/chronic lymphocytic leukemia [CLL], lymphoplasmacytic lymphoma [LPL], marginal zone lymphoma) or DLBCL (diffuse large B cell lymphoma)
- Patients must not be on strong inhibitors or inducers of CYP3A4 within two weeks prior to start of study treatment and for the duration of study treatment
- Patients must not be on anti-arrhythmic therapy other than digoxin or beta-blockers
- Patients with non-healing wound, ulcer, or bone fracture are not eligible
Patients with history of or current interstitial pneumonitis are not eligible
- NOTE: For solid tumors, cytomegalovirus (CMV) polymerase chain reaction (PCR) can be obtained at the discretion of treating physician or local institutional guidelines
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (copanlisib)
Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 of each cycle.
Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo tumor biopsies at screening and end of treatment and CT or MRI at baseline, every 2 cycles for the first 26 cycles, and then every 3 cycles thereafter until progressive disease or start of another MATCH treatment step.
|
Undergo MRI
Other Names:
Undergo tumor biopsy
Other Names:
Undergo CT
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (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 30 months post registration
|
ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable (ie, eligible, treated and PIK3CA mutation status confirmed) patients.
Objective response 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.
Details about how to define complete response and partial response can be found in the master protocol.
90% two-sided binomial exact confidence interval is calculated for 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 30 months post registration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
6-month Progression-Free Survival (PFS) Rate
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 rate is determined
|
Progression-free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. 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 NeuroOncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point. |
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 rate is determined
|
Progression Free Survival (PFS)
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
|
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. Please refer to the protocol for detailed definitions of disease progression. |
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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Senthilkumar Damodaran, ECOG-ACRIN Cancer Research Group
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplasms, Plasma Cell
- Neoplasms
- Lymphoma
- Multiple Myeloma
Other Study ID Numbers
- NCI-2022-06209 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U10CA180820 (U.S. NIH Grant/Contract)
- U24CA196172 (U.S. NIH Grant/Contract)
- EAY131-Z1F (Other Identifier: CTEP)
Plan for Individual participant data (IPD)
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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