Testing Copanlisib as Potentially Targeting Treatment in Cancers With PTEN Expression (MATCH - Subprotocol Z1H)

NCT ID: NCT06400238

Last Updated: 2025-11-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-15

Study Completion Date

2025-12-31

Brief Summary

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This phase II MATCH treatment trial tests how well copanlisib works in treating patients with cancer that has certain genetic changes. Copanlisib is used in patients whose cancer has a mutated (changed) form of a gene called PTEN. It is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells.

Detailed Description

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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 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

THE MATCH SCREENING TRIAL:

Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.

Conditions

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Advanced Lymphoma Advanced Malignant Solid Neoplasm Refractory Lymphoma Refractory Malignant Solid Neoplasm Refractory Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (copanlisib)

Patients receive copanlisib IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients undergo biopsies and blood sample collection on study.

Group Type EXPERIMENTAL

Biopsy Procedure

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Copanlisib

Intervention Type DRUG

Given IV

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Interventions

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Biopsy Procedure

Undergo biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT scan

Intervention Type PROCEDURE

Copanlisib

Given IV

Intervention Type DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Other Intervention Names

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Biopsy BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography BAY 80 6946 BAY 80-6946 BAY 806946 BAY-80-6946 BAY806946 PI3K Inhibitor BAY 80-6946 Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI

Eligibility Criteria

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Inclusion Criteria

* Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
* Patients must fulfill all eligibility criteria of MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7)
* Patients must have mutations in the PTEN gene with 1% or more expression of PTEN by immunohistochemistry (IHC) as determined via the MATCH Master Protocol

* NOTE: For patients entering the study, all patients must have PTEN IHC performed as described in the MATCH Master Protocol. This includes patients entering the study via the outside assay process
* Patients must not have co-existing aberrations in the MAPK or PI3K/MTOR pathways as determined by the MATCH screening assessment in NRAS, HRAS, KRAS, BRAF, PIK3CA, AKT or mTOR
* 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 must not have known hypersensitivity to copanlisib or compounds of similar chemical or biologic composition
* Patients must not have had prior treatment with copanlisib or other PI3K inhibitors, AKT inhibitors or mTOR inhibitors
* 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 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 a glycosylated hemoglobin (HbA1c) ≤ 8.5% within 28 days from registration
* Patients must not have uncontrolled hypertension defined as systolic blood pressure (SBP) greater than 160 mmHg or diastolic blood pressure (BP) greater than 100 mmHg or use of more than 2 anti-hypertensive medications
* Patients must not have HER2 positive (3+ by IHC or fluorescence in situ hybridization \[FISH\] ratio ≥ 2) breast cancer
* Patients must not have indolent NHL (non-Hodgkin's lymphoma) or DLBCL (diffuse large B cell lymphoma) because other studies are ongoing with this agent in this group of patients
* Patients must not be on anti-arrhythmic therapy other than digoxin or beta-blockers
* Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9 /L
* Platelets ≥ 100 x10\^9 /L
* Hemoglobin (Hb) \> 9 g/dl
* Total serum bilirubin \< 2.0 mg/dL
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5x upper limit of normal (ULN) (\< 5 x ULN in patients with liver metastases)
* Serum creatinine \< 1.5 x ULN
* 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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Filip Janku

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

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ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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NCI-2024-01162

Identifier Type: REGISTRY

Identifier Source: secondary_id

EAY131-Z1H

Identifier Type: OTHER

Identifier Source: secondary_id

EAY131-Z1H

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2024-01162

Identifier Type: -

Identifier Source: org_study_id