Copanlisib + Usual Treatment for Advanced Breast Cancer

Not currently recruiting at 17 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must be taking: Fulvestrant, Abemaciclib

Must not be taking: Immunosuppressants, Anti-arrhythmics

Disqualifiers: Brain metastasis, Autoimmune disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: 28 days per cycle, repeated until disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding copanlisib to the standard breast cancer treatments of fulvestrant and abemaciclib can improve outcomes for individuals with advanced hormone receptor-positive, HER2-negative breast cancer. Copanlisib, a type of targeted therapy, along with abemaciclib and fulvestrant, works to stop cancer cells from growing by blocking essential processes or hormones the cancer cells require. The trial seeks participants whose breast cancer has spread beyond the breast and who have had no more than one prior chemotherapy treatment for their metastatic cancer. Participants should have hormone receptor-positive, HER2-negative breast cancer and must be willing to provide a tumor sample for research. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new therapy.

Do I need to stop my current medications for the trial?

The trial requires a 'washout' period (time without taking certain medications) of at least 3 weeks from chemotherapy or 5 half-lives from oral targeted drugs before starting the study treatment. However, a washout from prior endocrine therapy is not required. You should also avoid certain medications that interact with the trial drugs, like strong inhibitors or inducers of CYP3A4.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is investigating the effectiveness of combining three drugs—copanlisib, abemaciclib, and fulvestrant—for advanced breast cancer. Previous studies have shown that abemaciclib and fulvestrant together are effective and generally well-tolerated. Researchers are now adding copanlisib to determine its safe use with these drugs.

Some side effects, common with cancer treatments, have been reported. These may include fatigue, nausea, or changes in blood tests. However, these side effects are usually manageable and can vary among individuals. The current research phase focuses on assessing the safety and tolerability of the combination, making safety a key priority. It is important to consult a healthcare provider about potential risks and benefits before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for advanced breast cancer, which often include hormone therapies like tamoxifen or aromatase inhibitors, the combination of copanlisib with abemaciclib and fulvestrant targets cancer in a novel way. Copanlisib works by inhibiting PI3K, a pathway that is crucial for cancer cell survival and growth, potentially leading to greater cancer cell death. Abemaciclib, a CDK4/6 inhibitor, stops cancer cells from dividing, while fulvestrant blocks and degrades estrogen receptors, cutting off the cancer's fuel supply. This multi-targeted approach is exciting because it could be more effective against cancer cells that have become resistant to standard treatments. Researchers are hopeful that this combination could offer a new lifeline for patients with advanced stages of the disease.

What evidence suggests that this trial's treatments could be effective for advanced breast cancer?

Research has shown that adding copanlisib to fulvestrant and abemaciclib may help treat advanced breast cancer. In this trial, participants will receive different dosages of this combination to evaluate its effectiveness and safety. Studies have found that fulvestrant blocks estrogen, which some cancer cells need to grow, while abemaciclib stops enzymes that help cancer cells multiply. Early results suggest that combining these drugs with copanlisib, which targets pathways cancer cells use to survive, might slow tumor growth. Initial data from trials indicate that this combination is manageable for patients and shows activity against tumors. ^{1 2 3 6 7}

Who Is on the Research Team?

Cynthia X Ma

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with hormone receptor positive, HER2 negative metastatic breast cancer. Participants must have recovered from previous treatments and agree to use contraception. They should not have had more than one chemotherapy in the metastatic setting or certain prior medications, and they can't join if they've had recent major surgeries, uncontrolled illnesses, or are pregnant.

Inclusion Criteria

Your heart's pumping ability is normal (LVEF >= 50%).

I have not had cancer treatment for 3 weeks or the required time for my medication.

Your lipase levels need to be within a certain range before starting the study treatment.

Exclusion Criteria

I do not have any severe illnesses like heart failure or uncontrolled high blood pressure that would stop me from following the study's requirements.

I am on medication for heart rhythm problems, but only beta blockers or digoxin.

I have a non-healing wound, ulcer, or bone fracture not caused by breast cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit (in-person)

Treatment

Patients receive copanlisib, abemaciclib, and fulvestrant in cycles of 28 days, with regular blood sample collections, tissue biopsies, and imaging

28 days per cycle, repeated until disease progression or unacceptable toxicity

Multiple visits per cycle for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3 months for 5 years

Follow-up visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Copanlisib Hydrochloride
• Fulvestrant

Trial Overview The study tests adding copanlisib to fulvestrant and abemaciclib (usual therapy) for advanced breast cancer. It's a phase I/II trial aiming to see if this combination works better than the usual therapy alone by blocking enzymes that help tumor cells grow.

How Is the Trial Designed?

Group I: Phase I Part B Dose 1b (copanlisib, abemaciclib, fulvestrant) Experimental Treatment 8 Interventions

Patients receive 45 mg copanlisib hydrochloride IV over 1 hour on days 1 and 15 and 100 mg abemaciclib PO twice daily BID for 5 days each week (2 days off). Patients also receive 500 fulvestrant IM on days 2 and 16 of cycle 1, and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an ECHO or MUGA scan during screening. Patients also undergo blood sample collection pre-treatment, cycle 1 days 1, 8, 15, and 22, cycle 2 day 1, cycle 4 day 1, cycle 7 day 1, and then every 3 cycles thereafter and at time of progression. Patients undergo tissue biopsy pre-treatment and optionally on cycle 1 day 15 and at the time of progression. Patients also undergo imaging at screening and at the completion of cycle 3, then every 3 cycles thereafter.

Group II: Phase I Part A Dose 2 (copanlisib, abemaciclib, fulvestrant) Experimental Treatment 8 Interventions

Patients receive 45 mg copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 and 150 mg abemaciclib PO twice daily BID for 5 days each week (2 days off). Patients also receive f500 mg fulvestrant IM on days 2 and 16 of cycle 1, and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an ECHO or MUGA scan during screening. Patients also undergo blood sample collection pre-treatment, cycle 1 days 1, 8, 15, and 22, cycle 2 day 1, cycle 4 day 1, cycle 7 day 1, and then every 3 cycles thereafter and at time of progression. Patients undergo tissue biopsy pre-treatment and optionally on cycle 1 day 15 and at the time of progression. Patients also undergo imaging at screening and at the completion of cycle 3, then every 3 cycles thereafter.

Group III: Phase I Part A Dose 1 (copanlisib, abemaciclib, fulvestrant) Experimental Treatment 8 Interventions

Patients receive 45 mg copanlisib hydrochloride IV over 1 hour on days 1 and 15 and 100 mg abemaciclib PO BID on days 2-28 of cycle 1 and on days 1-28 of subsequent cycles. Patients also receive 500 mg fulvestrant IM on days 2 and 16 of cycle 1, and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an ECHO or MUGA scan during screening. Patients also undergo blood sample collection pre-treatment, cycle 1 days 1, 8, 15, and 22, cycle 2 day 1, cycle 4 day 1, cycle 7 day 1, and then every 3 cycles thereafter and at time of progression. Patients undergo tissue biopsy pre-treatment and optionally on cycle 1 day 15 and at the time of progression. Patients also undergo imaging at screening and at the completion of cycle 3, then every 3 cycles thereafter.

Group IV: Phase I Part B Dose 2b (copanlisib, abemaciclib, fulvestrant) Active Control 8 Interventions

Patients receive 45 mg copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 and 100 mg abemaciclib PO twice daily BID for 5 days each week (2 days off). Patients also receive 500 mg fulvestrant IM on days 2 and 16 of cycle 1, and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an ECHO or MUGA scan during screening. Patients also undergo blood sample collection pre-treatment, cycle 1 days 1, 8, 15, and 22, cycle 2 day 1, cycle 4 day 1, cycle 7 day 1, and then every 3 cycles thereafter and at time of progression. Patients undergo tissue biopsy pre-treatment and optionally on cycle 1 day 15 and at the time of progression. Patients also undergo imaging at screening and at the completion of cycle 3, then every 3 cycles thereafter.

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03939897

NCT03939897 | Testing the Addition of Copanlisib to Usual ... This phase I trial studies the effects (good and bad) of adding copanlisib to the usual therapy of fulvestrant and abemaciclib in treating patients with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11936477/

Abemaciclib Plus Fulvestrant in Advanced Breast Cancer After ... We report outcomes of the postMONARCH trial investigating a switch in ET with/without CDK4/6 inhibition with abemaciclib after disease progression on CDK4/6i.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03939897?term=AREA%5BBasicSearch%5D(AREA%5BInterventionSearch%5D(COPANLISIB%20HYDROCHLORIDE)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL))&rank=9

Testing the Addition of Copanlisib to Usual Treatment ... It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

4. clinicaltrials.med.nyu.edu clinicaltrials.med.nyu.edu/clinicaltrial/1367/randomized-phase-iii-trial/

A randomized Phase I/II trial of fulvestrant and abemaciclib in ... The purpose of the study is to determine the effects (good and bad) of adding copanlisib to the usual therapy of fulvestrant and abemaciclib in treating ...

5. vjoncology.com vjoncology.com/video/2hvrrcw6r4w-copanlisib-and-fulvestrant-with-abemaciclib-in-her-er-breast-cancer/

SABCS 2023 | Copanlisib and fulvestrant with abemaciclib in ... Copanlisib and fulvestrant with intermittent abemaciclib were found to be tolerable, where preliminary anti-tumor activity was reported. This ...

6. ascopost.com ascopost.com/videos/2023-sabcs/cynthia-ma-on-metastatic-breast-cancer-early-results-on-copanlisib-fulvestrant-and-abemaciclib/

Cynthia X. Ma, MD, PhD, on Metastatic Breast Cancer Louis, discusses phase I findings showing the safety and tolerability of copanlisib and fulvestrant in combination with continuous or intermittent abemaciclib ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39249111/

Efficacy and Safety of Abemaciclib in Combination With ... Abemaciclib, a CDK4/6 inhibitor, has shown promising results in treating advanced cases. This study comprehensively assesses the efficacy and ...