Fulvestrant and Palbociclib With or Without Copanlisib in Treating Patients With Hormone Receptor Positive, HER2 Negative, Stage IV Breast Cancer

NCT03377101 | Withdrawn Phase 2 FDA Drug

• 3 other identifiers: NCI-2017-0232010194UM1CA186704
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This randomized phase II trial studies the side effects and how well fulvestrant and palbociclib with or without copanlisib work in treating patients with hormone receptor positive, HER2 negative, stage IV breast cancer. Fulvestrant, palbociclib, and copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Estrogen Receptor Positive; HER2/Neu Negative; Progesterone Receptor Positive; Stage IV Breast Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity based on the incidence, intensity, and duration of adverse events that are related to the drug combinations and occur according to according to National Cancer Institute Common Terminology Criteria for Adverse Event version 4.0

  Adverse events will be summarized by counts and percentages, overall as well as by does levels and by patient characteristics.

  Up to 28 days

• Progression free survival (PFS)

  PFS probability will be estimated by the Kaplan-Meier (KM) product limit method and survival difference will be compared between the two arms by stratified log rank test. Hazard ratio (HR) with 95% confidence interval (CI) will be estimated between the two arms from the stratified Cox proportional hazard model, without and with adjustment for patient characteristics.

  From the time on study to the time of disease progression or death or end of study, whichever earlier, assessed up to 5 years

Secondary Outcomes (3)

• Objective response rate defined as proportion of response-evaluable patients who achieve complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1

  Up to 5 years

• Clinical benefit rate defined as proportion of response-evaluable patients who achieve CR or PR or stable of disease (SD) according to RECIST v1.1

  Up to 5 years

• Overall survival (OS) according to RECIST v1.1

  From time on study to time of death or latest follow-up, whichever earlier, assessed up to 5 years

Study Arms (2)

Arm I (fulvestrant, palbociclib)

ACTIVE COMPARATOR

Patients receive fulvestrant IM on days 1 and 15 of course 1 and day 1 of subsequent courses and palbociclib PO on days 1-21. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.

Drug: Fulvestrant; Other: Laboratory Biomarker Analysis; Drug: Palbociclib

Arm I (fulvestrant, palbociclib, copanlisib)

EXPERIMENTAL

Patients receive fulvestrant IM on days 1 and 15 of course 1 and day 1 of subsequent courses, palbociclib PO on days 1-21, and copanlisib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in absence of disease progression or unacceptable toxicity.

Drug: Copanlisib; Drug: Fulvestrant; Other: Laboratory Biomarker Analysis; Drug: Palbociclib

Interventions

Copanlisib DRUG

Given IV

Also known as: BAY 80-6946, PI3K Inhibitor BAY 80-6946

Arm I (fulvestrant, palbociclib, copanlisib)

Fulvestrant DRUG

Given IM

Also known as: Faslodex, Faslodex(ICI 182,780), ICI 182,780, ICI 182780, ZD9238

Arm I (fulvestrant, palbociclib); Arm I (fulvestrant, palbociclib, copanlisib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (fulvestrant, palbociclib); Arm I (fulvestrant, palbociclib, copanlisib)

Palbociclib DRUG

Given PO

Also known as: Ibrance, PD-0332991, PD-332991

Arm I (fulvestrant, palbociclib); Arm I (fulvestrant, palbociclib, copanlisib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed estrogen receptor (ER) and/or progesterone receptor (PR) positive, HER2 negative or non-amplified breast cancer that is stage IV, with measurable or non-measurable disease; ER/PR positivity is defined as at least 1% positive or Allred score of at least 3
• All patients must agree to provide archival tumor material for research and must agree to undergo research tumor biopsy before treatment if presence of easily accessible lesions (judged by the treating physician); for patients with bone only disease, or patients without easily accessible lesions for the baseline research biopsy, availability of archival tumor material (2 x 4-5 micron section unstained slides, plus 15-20 x 10 micron section unstained slides or a tumor rich block) from previous breast cancer diagnosis or treatment is required for PTEN and PIK3CA analysis
• No more than 1 prior chemotherapy in the metastatic setting; there is no limit on prior lines of endocrine therapy; (for patients enrolling to the safety run-in portion of the study, prior fulvestrant, CDK4/6 inhibitor, and everolimus is allowed)
• For patients enrolling to the randomized phase II portion of this study, demonstrated resistance to prior endocrine therapy in the metastatic setting is required; this is defined as:
• Progressed on prior endocrine therapy in the metastatic setting or
• Relapsed on adjuvant endocrine therapy or
• Relapsed within 12 months of completing adjuvant endocrine therapy or
• If received adjuvant CDK4/6 inhibitor, relapsed at least 2 years after completion of adjuvant CDK4/6 inhibitor
• Washout from prior systemic anti-cancer therapy of at least 3 weeks or 5 half-lives of the drug before the start of study treatment; washout from prior radiation therapy of at least 2 weeks before the start of the study treatment
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Absolute neutrophil count \>= 1,500/mcL collected no more than 7 days before starting study treatment
• Platelets \>= 75,000/mcL collected no more than 7 days before starting study treatment
• Hemoglobin \>= 8.0 g/dL collected no more than 7 days before starting study treatment
• Total bilirubin =\< 1.5 x institutional upper limit of normal (=\< 3 x institutional upper limit of normal for patients with Gilbert syndrome) collected no more than 7 days before starting study treatment
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (=\< 5 x institutional upper limit of normal for patients with liver involvement) collected no more than 7 days before starting study treatment

You may not qualify if:

• For patients enrolling to the randomized phase II portion of the study, prior treatment with a CDK4/6 inhibitor or fulvestrant, or a PI3K inhibitor in the metastatic setting is not allowed
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1 with the exception of alopecia)
• Immunosuppressive therapy is not allowed while on study
• Patients who are receiving any other investigational agents
• Receiving anti-arrhythmic therapy (beta blockers or digoxin are permitted)
• Patients with brain metastasis are not eligible for the randomized phase II portion of the study; for the safety run-in portion of the study, patients with progressive brain metastases should be excluded; for patients enrolling to the randomized phase II portion of the study, patients with a history of brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to copanlisib, PI3K inhibitors, or other agents used in study
• The concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and strong inducers of CYP3A4 (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, St. John's wort) are not permitted from 14 days prior to enrollment until the end of the study; other medications that are prohibited while on copanlisib treatment:
• Herbal medications/preparations (except for vitamins)
• Anti-arrhythmic therapy other than beta blockers or digoxin
• Systemic corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not permitted while on study; previous corticosteroid therapy must be stopped or reduced to the allowed dose at least 7 days prior to the computed tomography (CT)/magnetic resonance imaging (MRI) screening; if a patient is on chronic corticosteroid therapy, corticosteroids should be de-escalated to the maximum allowed dose before the screening; patients may be using topical or inhaled corticosteroids; short-term (up to 7 days) systemic corticosteroids above 15 mg prednisolone or equivalent will be allowed for the management of acute conditions (e.g., treatment non-infectious pneumonitis); the use of corticosteroids as antiemetics prior to copanlisib administration will not be allowed
• Major surgical procedure or significant traumatic injury (as judged by the investigator) within 28 days before start of treatment, or have not recovered from major side effects, open biopsy within 7 days before start of treatment
• 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, cardiac arrhythmia, uncontrolled hypertension despite optimal medical management, seizure disorder requiring medication, or psychiatric illness/social situations that would limit compliance with study requirements
• Proteinuria \>= grade 3 as assessed by a 24 hour \[h\] protein quantification or estimated by urine protein: creatinine ratio \> 3.5 on a random urine sample

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Interventions

copanlisib; Fulvestrant; palbociclib

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Cynthia Ma

  Duke University - Duke Cancer Institute LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: December 19, 2017
• Study Start: August 7, 2018
• Primary Completion: August 7, 2018
• Study Completion: August 7, 2018
• Last Updated: August 14, 2018

Record last verified: 2018-07