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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates how well copanlisib treats cancers with specific genetic changes in the PTEN gene. Copanlisib blocks certain proteins that signal cancer cells to grow, potentially slowing or stopping the cancer's spread. Ideal candidates have cancer with a PTEN mutation and lack certain other genetic changes or uncontrolled health conditions like severe high blood pressure. Participants receive copanlisib through an IV on a set schedule, with regular scans and tests to monitor progress. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important cancer research.

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.

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

Research has shown that copanlisib is generally well-tolerated by patients. In studies, patients taking copanlisib experienced lasting positive results, with the treatment remaining effective over time. For instance, one study of patients with relapsed or refractory indolent follicular lymphoma found copanlisib effective for up to six years. Additionally, when combined with nivolumab, copanlisib was well-tolerated in individuals with advanced solid tumors.

Most patients experienced manageable side effects. However, like any medication, some unwanted effects may occur, so discussing these with a healthcare team is important. Current data suggests that copanlisib is a promising option for treating certain cancers, and ongoing research continues to explore its safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Copanlisib is unique because it targets the PI3K pathway, a key player in cancer cell growth and survival. Unlike many standard treatments that might target more general cancer mechanisms, copanlisib specifically inhibits PI3K, potentially leading to more effective cancer control with fewer off-target effects. Additionally, it's administered intravenously, allowing for precise control over dosing and timing. Researchers are excited about copanlisib's ability to home in on this specific pathway, offering hope for better outcomes in patients who haven't responded to other treatments.

What evidence suggests that copanlisib might be an effective treatment for cancer?

Research has shown that copanlisib may help treat different types of cancer by blocking certain proteins that cause cancer cells to grow. In one study, 59% of lymphoma patients experienced their cancer shrinking or stopping its growth after using copanlisib. Some patients even had a complete response, with no signs of cancer found. These results suggest that copanlisib could be effective for cancers with specific genetic changes, such as those involving the PTEN gene. ^{1 2 4 6 7}

Who Is on the Research Team?

Filip Janku

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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 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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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 ... Median overall survival was 46.3 months (range 0.7-82.9) with a total of 56 events and a median follow-up of 82.4 months (95% CI 79.3, 84.9); ...

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39927513/

A Phase Ib Study in Patients with Advanced Solid Tumors The combination of copanlisib and nivolumab was well tolerated and showed antitumor effects in patients with advanced solid tumors.

4. 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 ( ...

5. aacrjournals.org aacrjournals.org/cancerdiscovery/article/7/12/OF2/40408/Copanlisib-Produces-Prolonged-Responses-in

Copanlisib Produces Prolonged Responses in Lymphoma After a median of 22 weeks of treatment, the objective response rate was 59%, with 12% of the patients showing a complete response. The median response duration ...

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 ... Significance: The combination of copanlisib and nivolumab was well tolerated and showed antitumor effects in patients with advanced solid tumors.

7. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.3173

Model‐Based Benefit/Risk Analysis for the Copanlisib ... Within the exposure-safety dataset, a total of 402 (90.5%) of copanlisib-treated patients (monotherapy from CHRONOS-1 or in combination with ...