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CDK4/6 Inhibitor

Copanlisib + Usual Treatment for Advanced Breast Cancer

Phase 1 & 2

Waitlist Available

Led By Cynthia X Ma

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age >= 18 years

Washout from prior systemic anti-cancer therapy of at least 3 weeks from chemotherapy or 5 half-lives from oral targeted drugs, and treatment related adverse events recovered to grade 1 (except for alopecia) before the start of study treatment. Washout from prior radiation therapy of at least 2 weeks before the start of the study treatment. Washout from prior endocrine therapy is not required

Must not have

Uncontrolled intercurrent illness, including but not limited to, symptomatic congestive heart failure (> New York Heart Association [NYHA] class 2), unstable angina pectoris, new-onset angina, uncontrolled hypertension despite optimal medical management, seizure disorder requiring medication, or psychiatric illness/social situations that would limit compliance with study requirements

Patients with non-healing wound, ulcer, or bone fracture not due to breast cancer

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is studying the effects of adding copanlisib to the usual therapy of fulvestrant and abemaciclib in treating patients with hormone receptor positive and HER2 negative stage IV breast cancer.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include blood disorders, high blood sugar levels, fatigue, digestive issues like diarrhea or liver problems. There may also be risks of infection due to lowered immune function and possible heart-related side effects.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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

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My breast cancer is ER/PR positive, HER2 negative, and stage IV.

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My kidney function, measured by GFR, is at least 30 mL/min.

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I can take care of myself but might not be able to do heavy physical work.

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I had hepatitis C but am cured, or I'm being treated with no detectable virus.

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My hepatitis B virus load is undetectable with treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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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.

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

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I haven't had serious bleeding issues in the last month.

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I have never had brain metastasis.

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I am allergic to certain cancer drugs similar to those used in this study.

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I am not taking certain strong medications that affect how my body processes the study drug.

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I haven't had major surgery or serious injury in the last 28 days, nor an open biopsy in the last 7 days.

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I have had major surgery on my stomach or intestines, or I have Crohn's, ulcerative colitis, or chronic diarrhea.

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I have been diagnosed with pheochromocytoma.

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My protein levels in urine are very high.

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I am not pregnant or breastfeeding.

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I have had a bone marrow or organ transplant from another person.

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I haven't had chemotherapy in the last 3 weeks or radiotherapy in the last 2 weeks.

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I haven't had a stroke, clot, or embolism in the last 3 months.

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I have a lung condition or severe breathing problems.

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I do not have a serious infection.

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I am not on immunosuppressive therapy.

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I do not have worsening brain metastases.

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I have a history of serious heart conditions, including fainting due to heart issues, dangerous irregular heartbeats, or sudden cardiac arrest.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose-limiting Toxicity (DLT) (Phase I)

Progression-free Survival (PFS) (Phase II)

Secondary study objectives

Change in Tumor pAKT Levels (Phase II)

Clinical Benefit Rate (Phase II)

Effectiveness of Fulvestrant, Abemaciclib, and Copanlisib (FAC) Compared to Fulvestrant and Abemaciclib (FA) (Phase II)

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Active Control

Group I: Phase II, Arm I (FAC) (copanlisib, abemaciclib, fulvestrant)Experimental Treatment8 Interventions

Patients receive copanlisib hydrochloride as in phase I. Patients also receive abemaciclib PO BID on days 1-28 and fulvestrant IM on days 1 and 15 of cycle 1 and 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 B Dose Level 2b (copanlisib, abemaciclib, fulvestrant)Experimental Treatment8 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.

Group III: Phase I Part B Dose Level 1b (copanlisib, abemaciclib, fulvestrant)Experimental Treatment8 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 IV: Phase I Part A Dose Level 2 (copanlisib, abemaciclib, fulvestrant)Experimental Treatment8 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 ulvestrant 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 V: Phase I Part A Dose Level 1 (copanlisib, abemaciclib, fulvestrant)Experimental Treatment8 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 VI: Phase II, Arm II (FA) (abemaciclib, fulvestrant)Active Control7 Interventions

Patients receive abemaciclib PO BID on days 1-28 and fulvestrant IM on days 1 and 15 of cycle 1 and 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 and ECG during screening and as clinically indicated. 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fulvestrant

2011

Completed Phase 3

~3790

Biopsy

2014

Completed Phase 4

~1150