Copanlisib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers, Anti-arrhythmics

Disqualifiers: Diabetes, Hypertension, HER2 positive, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: Up to 3 years

35 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop using herbal medications at least 7 days before starting copanlisib. You also cannot be on strong inhibitors or inducers of CYP3A4 within two weeks before starting and during the study. If you are on anti-arrhythmic therapy, only digoxin or beta-blockers are allowed.

How is the drug Copanlisib unique in treating cancer?

Copanlisib is unique because it is an intravenous drug that targets the PI3K pathway, which is involved in cancer cell growth, and it has shown effectiveness in treating certain types of lymphoma and solid tumors. Unlike some other treatments, it is specifically designed to inhibit multiple forms of the PI3K enzyme, potentially overcoming resistance mechanisms in cancer cells. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Research Team

Filip Janku

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for patients with various types of cancer, including lymphoma and multiple myeloma, that have a specific genetic change in the PTEN gene. Participants should be willing to undergo biopsies and imaging tests like CT or MRI scans as part of the study.

Inclusion Criteria

Platelets ≥ 100 x10^9 /L

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)

Exclusion Criteria

I have never had interstitial pneumonitis.

For solid tumors, cytomegalovirus (CMV) polymerase chain reaction (PCR) can be obtained at the discretion of treating physician or local institutional guidelines

My cancer does not have mutations in specific genes related to growth pathways.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive copanlisib IV over 60 minutes on days 1, 8, and 15 of each 28-day cycle

Up to 3 years

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Every 3 months for 2 years, then every 6 months for 1 year

Treatment Details

Interventions

• Copanlisib

Trial Overview The focus of this phase II trial is on Copanlisib, a kinase inhibitor medication designed to block abnormal proteins that cause cancer cells to grow. The goal is to see if it can slow down or stop these cells from spreading in cancers with altered PTEN genes.

Participant Groups

Group I: Treatment (copanlisib) Experimental Treatment 5 Interventions

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Copanlisib is effective in treating relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL), with an overall response rate of 57% and a complete response rate of 13% based on a meta-analysis of 652 patients across 8 studies.

Combination therapy with copanlisib and rituximab showed significantly higher efficacy compared to copanlisib alone, with complete response rates of 34% versus 6%, while treatment-related adverse events were manageable, with common side effects including hyperglycemia and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of copanlisib in relapsed/refractory B-cell non-Hodgkin lymphoma: A meta-analysis of prospective clinical trials. Wang, J., Zhou, H., Mu, M., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

A Phase I study of intravenous PI3K inhibitor copanlisib in Japanese patients with advanced or refractory solid tumors. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

On-Target Pharmacodynamic Activity of the PI3K Inhibitor Copanlisib in Paired Biopsies from Patients with Malignant Lymphoma and Advanced Solid Tumors. [2021]

3. England pubmed.ncbi.nlm.nih.gov

First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of copanlisib in combination with gemcitabine or cisplatin plus gemcitabine in patients with advanced cancer. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of copanlisib in relapsed/refractory B-cell non-Hodgkin lymphoma: A meta-analysis of prospective clinical trials. [2022]