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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests copanlisib, a drug that might stop or shrink cancer in individuals with a specific genetic change called a PIK3CA mutation. Copanlisib blocks a protein that aids cancer cell growth. The goal is to determine if this drug can effectively control cancer growth. Individuals with cancer featuring the PIK3CA mutation who have not previously taken drugs like copanlisib might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that copanlisib hydrochloride is likely to be safe for humans?

Research has shown that copanlisib is generally well-tolerated by patients. In previous studies, common side effects included high blood sugar (experienced by about 63 out of 100 patients) and high blood pressure (noted in about 50 out of 100 patients). Other side effects included nausea and a decrease in certain blood cells.

Importantly, long-term use of copanlisib did not reveal any new safety issues, nor did it worsen the cancer. These results, based on its use in different types of cancer, suggest a consistent safety record. While side effects can occur, they are manageable, which is encouraging for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard cancer treatments, which often include chemotherapy or targeted therapies like tyrosine kinase inhibitors, copanlisib works uniquely by inhibiting PI3K, a key protein involved in cancer cell growth and survival. This new mechanism of action is exciting because it specifically targets a pathway that many cancers use to thrive, potentially leading to more effective treatment outcomes. Additionally, copanlisib is administered intravenously, which allows for precise control over dosing and could result in fewer side effects compared to oral medications. Researchers are optimistic that copanlisib's targeted approach may offer a new hope for patients whose cancers are resistant to existing therapies.

What evidence suggests that copanlisib might be an effective treatment for cancer with a PIK3CA mutation?

Research has shown that copanlisib could effectively treat cancers with a specific genetic change called the PIK3CA mutation. Studies have found that it stops cancer cells from growing by blocking a protein called PIK3, which is crucial for cell growth. In patients with recurring or hard-to-treat cancers like follicular lymphoma, copanlisib led to a strong response and longer survival. Patients experienced a quick and noticeable decrease in tumor size, and the treatment had lasting effects. Additionally, when combined with other drugs, copanlisib further improved the ability to stop tumor growth. These findings suggest that copanlisib might be a promising option for people with certain genetic changes in their cancer. Participants in this trial will receive copanlisib as part of the treatment regimen. ^{1 2 5 6 7}

Who Is on the Research Team?

Senthilkumar Damodaran

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.7555

Six-year safety and efficacy results from the CHRONOS-1 ... Copanlisib continued to induce robust response and durable survival in patients with relapsed or refractory indolent FL at 6 years of follow-up.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7876879/

Efficacy and safety of copanlisib in patients with relapsed ... Overall, copanlisib demonstrated strong efficacy, with a short time to objective response, improved objective response rate with longer ...

3. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1034253/full

Efficacy and safety of copanlisib in relapsed/refractory B ... The results indicated that copanlisib had promising efficacy in patients with R/R B-NHL who failed to respond to previous antitumor therapy.

4. aacrjournals.org aacrjournals.org/cancerrescommun/article/4/6/1430/745713/Evaluation-of-Copanlisib-in-Combination-with

Evaluation of Copanlisib in Combination with Eribulin in Triple ... Compared with each drug alone, the combination of eribulin and copanlisib led to enhanced tumor growth inhibition, which was observed in both ...

5. hematologyadvisor.com hematologyadvisor.com/reports/follicular-lymphoma-copanlisib-patients-benefit-durable-survival-treatment/

Copanlisib May Benefit Patients With Follicular Lymphoma Survival rates indicated a median overall survival (OS) of 46.3 months (range, 0.7-82.9) with a total of 56 events and a median follow-up of ...

6. aacrjournals.org aacrjournals.org/cancerrescommun/article/5/3/444/754187/Safety-and-Efficacy-of-Copanlisib-in-Combination

Safety and Efficacy of Copanlisib in Combination with ... The combination of copanlisib and nivolumab was well tolerated and showed antitumor effects in patients with advanced solid tumors. The number of circulating ...

7. ashpublications.org ashpublications.org/bloodadvances/article/8/18/4866/517175/CHRONOS-4-phase-3-study-of-copanlisib-plus

CHRONOS-4: phase 3 study of copanlisib plus rituximab ... The most common treatment-emergent AEs (TEAEs) of any grade were hyperglycemia (57.8%), hypertension (44.1%), nausea (42.6%), and decreased neutrophil count ( ...