Copanlisib + Usual Treatment for Advanced Breast Cancer

Recruiting at 13 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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

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 hormone receptor positive and HER2 negative breast cancer that has spread from where it first started (breast) to other places in the body (metastatic). Some breast cancer cells have receptors for the hormones estrogen or progesterone. These cells are hormone receptor positive and they need estrogen or progesterone to grow. This can affect how the cancer is treated. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. Abemaciclib and copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Adding copanlisib to the usual therapy of fulvestrant and abemaciclib may work better than giving fulvestrant and abemaciclib alone in treating patients with breast cancer.

Research Team

Cynthia X Ma

Principal Investigator

Yale University Cancer Center LAO

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+