A Study of a New Drug Combination, Copanlisib and Fulvestrant, in Advanced Breast Cancer

NCT03803761 | Withdrawn Phase 1 DMC FDA Drug

• 4 other identifiers: NCI-2019-00048NCI1019510195UM1CA186704
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 7

Brief Summary

This phase I/II trial studies the side effects and how well copanlisib works when given together with fulvestrant in treating patients with estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-) breast cancer that has spread to other places in the body (advanced) and progressing after prior treatment. HER2 and ER are two types of proteins called receptors that can affect the growth of breast cancer cells. Additionally, investigators hope to learn from this study if tumor genetic information is important for predicting whether this type of breast cancer will respond to fulvestrant and copanlisib. Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving copanlisib and fulvestrant may work better in treating patients with ER+ and HER2- breast cancer compared to fulvestrant alone.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Breast Carcinoma; Metastatic Malignant Neoplasm in the Brain; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT)

  Toxicities will be tabulated based on type and grade.

  Up to 30 days post treatment

Secondary Outcomes (3)

• Progression-free survival (PFS)

  From start of treatment to time of progression or death, assessed up to 30 days post treatment

• Response rate

  Up to 30 days post treatment

• Incidence of adverse events

  Up to 30 days post treatment

Other Outcomes (2)

• Pharmacokinetics (PK) and pharmacodynamic data (RPPA)

  Up to 30 days post treatment

• Biomarkers analysis

  Up to 30 days post treatment

Study Arms (1)

Treatment (copanlisib, fulvestrant)

EXPERIMENTAL

Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 and fulvestrant IM over 1-2 minutes on days 1 and 15 of cycle 1 and on day 1 beginning cycle 2. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Copanlisib; Drug: Fulvestrant

Interventions

Copanlisib DRUG

Given IV

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

Treatment (copanlisib, fulvestrant)

Fulvestrant DRUG

Given IM

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

Treatment (copanlisib, fulvestrant)

Eligibility Criteria

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

You may qualify if:

• Postmenopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer (MBC) who have progressed on combination therapy with an aromatase inhibitor and cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor
• Note: Postmenopausal females are considered of childbearing potential unless they are surgically or permanently sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. Documentation of postmenopausal status must be provided
• Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1)
• Patients must have had tumor sequencing for evaluation of actionable PIK3CA or PTEN mutations performed in a Clinical Laboratory Improvement Act (CLIA) certified, College of American Pathologist (CAP) tested and bioinformatics-validated testing lab PRIOR to enrollment in this current protocol. If available patient tumor sequencing status must be provided to University of North Carolina (UNC) principal investigator (PI) at consent, and prior to any additional screening procedures. The testing may have been done at any time prior to enrollment. For patients who have not yet had tumor genomic assessment, after consultation with the PI, tumor specimens will be sent to the UNC Hospitals Clinical Molecular Genetics Laboratory for assessment of the Solid Tumor Mutation Panel. In this case, results of genetic testing by the UNC lab must be available prior to the first on study disease assessment (i.e., prior to day 1 of cycle 4). In this case, the study will cover the cost of the Solid Tumor Panel
• Female subjects who are not of childbearing potential
• Note: Because no dosing or adverse event data are currently available on the use of copanlisib in combination with fulvestrant in patients \<18 years of age, and only postmenopausal women with ER+/HER2 negative MBC are eligible or appropriate for treatment with fulvestrant, children and pregnant or pre-menopausal women are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• No prior treatment history with fulvestrant or a PI3K inhibitor
• Subject has not received more than 2 prior lines of chemotherapy in the metastatic setting
• Subject must have washout period from prior systemic anti-cancer therapy of at least 21 days (or 5 half-lives of the systemic anti-cancer therapy, whichever is shorter) before the start of study treatment
• Subject must have washout period from prior radiation therapy of at least 2 weeks before the start of study treatment
• Subjects with a history of brain metastases are allowed if they are not on steroid therapy and there is no evidence of intracranial disease progression symptomatically or by imaging within 28 days prior to study registration
• Hemoglobin \>= 9.0 g/dL (collected no more than 7 days before starting treatment)
• Leukocytes \>= 3,000/mcL (collected no more than 7 days before starting treatment)
• Absolute neutrophil count \>= 1,500/mcL (collected no more than 7 days before starting treatment)

You may not qualify if:

• Previous assignment to treatment during this study. Patients permanently withdrawn from study participation will not be allowed to re-enter the study
• Concomitant participation in another clinical study with investigational medicinal product
• Subjects 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
• Subjects who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to copanlisib, fulvestrant, or PI3K inhibitors
• Subjects with moderate or severe hepatic impairment (ie, Child-Pugh B or C)
• Copanlisib is primarily metabolized by CYP3A4. Therefore, 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
• Uncontrolled intercurrent illness, including but not limited to, psychiatric illness/social situations that would limit compliance with study requirements
• Major surgical procedure or significant traumatic injury (as judged by the investigator) within 28 days prior to start of treatment, or not recovered from major side effects, or open biopsy within 7 days before start of study treatment
• Patients with non-healing wound, ulcer, or bone fracture not due to breast cancer
• Patients with active, clinically serious infections \> grade 2 (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5.0)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0565, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

copanlisib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

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

• Elizabeth C Dees

  Duke University - Duke Cancer Institute LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2019
• First Posted: January 15, 2019
• Study Start: February 13, 2019
• Primary Completion: February 19, 2022
• Study Completion: February 19, 2022
• Last Updated: September 25, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share

Locations

US (7)