Copanlisib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, Anti-arrhythmics

Disqualifiers: KRAS mutations, HER2 positive, NHL, 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 30 months

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II MATCH treatment trial identifies the effects of copanlisib hydrochloride (copanlisib) in patients whose cancer has a genetic change called PIK3CA mutation. Copanlisib may stop the growth of cancer cells by blocking PIK3, a protein needed for cell growth. Researchers hope to learn if copanlisib will shrink this type of cancer or stop its growth.

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. Additionally, you cannot be on strong inhibitors or inducers of CYP3A4 or anti-arrhythmic therapy other than digoxin or beta-blockers during the study.

What data supports the effectiveness of the drug Copanlisib Hydrochloride for cancer?

Research shows that Copanlisib, a drug that blocks a specific pathway in cancer cells, has shown positive effects in treating certain types of lymphoma and solid tumors. In studies, it has led to tumor shrinkage in some patients and has been found to be safe when used alone or with other cancer drugs. ^{1 2 3 4 5}

Is copanlisib safe for humans?

Copanlisib is generally well-tolerated in humans, but it can cause some side effects like high blood sugar and high blood pressure during infusion, which usually go away soon after. Other less common side effects include lung inflammation, infections, diarrhea, and liver issues. ^{1 3 5 6 7}

How is the drug Copanlisib different from other cancer treatments?

Copanlisib is unique because it is an intravenous drug that targets a specific pathway in cancer cells called the PI3K pathway, which is often altered in certain cancers. This makes it different from other treatments that may not specifically target this pathway, potentially offering a new approach for patients with cancers that have become resistant to other therapies. ^{1 2 3 5 8}

Research Team

Senthilkumar Damodaran

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for cancer patients with a specific genetic change called PIK3CA mutation. They must meet prior MATCH Protocol criteria, have certain blood cell counts and organ function levels, not use herbal medications or strong CYP3A4 inhibitors, and agree to contraception. It's not for those with hypersensitivity to copanlisib, previous PI3K inhibitor treatments, activating KRAS mutations, HER2 positive breast cancer, heart rhythm issues or non-healing wounds.

Inclusion Criteria

Your hemoglobin level is higher than 9 grams per deciliter.

Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol

Your absolute neutrophil count is at least 1.5 billion per liter.

Exclusion Criteria

I am not taking strong CYP3A4 inhibitors or inducers.

I do not have slow-growing types of non-Hodgkin lymphoma or diffuse large B-cell lymphoma.

I do not have a history of or current lung inflammation.

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 1 hour on days 1, 8, and 15 of each 28-day cycle

Up to 30 months

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Every 3 months for the first 2 years, then every 6 months for year 3

Treatment Details

Interventions

• Copanlisib Hydrochloride

Trial Overview The trial tests the drug copanlisib hydrochloride on various cancers with the PIK3CA mutation. Copanlisib aims to halt cancer growth by inhibiting a protein essential for cell proliferation. The study involves biopsies and imaging like CT scans and MRIs to monitor effects.

Participant Groups

Group I: Treatment (copanlisib) Experimental Treatment 4 Interventions

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.

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. 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]

2. 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]

3. 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]

4. 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]

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]

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

Copanlisib: An Intravenous Phosphatidylinositol 3-Kinase (PI3K) Inhibitor for the Treatment of Relapsed Follicular Lymphoma. [2020]

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

Optimal Management of Adverse Events From Copanlisib in the Treatment of Patients With Non-Hodgkin Lymphomas. [2020]

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

Phase I trial of copanlisib, a selective PI3K inhibitor, in combination with cetuximab in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. [2022]