Copanlisib, Letrozole, and Palbociclib in Treating Patients With Hormone Receptor Positive HER2 Negative Stage I-IV Breast Cancer

Stage IV Breast Cancer Clinical Trial

Official title: A Phase Ib Trial Evaluating the Safety of Copanlisib, Letrozole, and Palbociclib in Metastatic Breast Cancer and Phase II Trial Comparing the Molecular Effects of Neoadjuvant Copanlisib in Combination With Palbociclib and Letrozole, vs. Copanlisib With Letrozole, vs. Palbociclib With Letrozole for Patients With Hormone Receptor Positive, HER2 Normal Breast Cancer

Status Terminated

Clinical Trial Summary

This phase I/II trial studies side effects and best dose of copanlisib when given together with letrozole and palbociclib and to see how well they work in treating hormone receptor positive HER2 negative stage I-IV breast cancer. Copanlisib and palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs, such as letrozole, may lessen the amount of estrogen made by the body. Giving copanlisib, letrozole, and palbociclib may work better in treating patients with breast cancer.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Assess the safety, tolerability and to estimate the maximum tolerated dose (MTD) in a metastatic setting of the following combination: copanlisib + palbociclib + letrozole. (Phase Ib) II. Compare the biological activity of letrozole in combination with palbociclib, letrozole in combination with palbociclib and copanlisib, and letrozole in combination with copanlisib by assessing the percentage change from the baseline value in Ki67 expression after 2 weeks of therapy in non-metastatic breast cancer. (Phase II)

SECONDARY OBJECTIVES:

I. Evaluate the pathologic complete response (pCR) defined as absence of invasive cancer in the breast and sampled regional lymph nodes.

II. Evaluate the clinical objective response Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1.

III. Assess safety and tolerability. IV. Evaluate the pharmacokinetics of copanlisib when given in combination with letrozole, and palbociclib.

V. Measure the gene expression and/or biomarker changes that may be correlated with or predict biological, clinical, and pathologic response.

OUTLINE: This is a dose-escalation study of copanlisib.

PHASE Ib: Patients with metastatic breast cancer receive copanlisib intravenously (IV) over 1 hour on days 1, 8, and 15, palbociclib orally (PO) once daily (QD) on days 1-21, and letrozole PO continuously on days 1-28. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: After determination of MTD, subsequent non-metastatic breast cancer patients are randomized to 1 of 3 arms:

ARM A: Patients receive copanlisib (MTD) IV over 1 hour on days 1, 8, and 15 and letrozole PO continuously on days 1-28. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression, or unacceptable toxicity.

ARM B: Patients receive copanlisib (MTD) IV over 1 hour on days 1, 8, and 15, palbociclib PO QD on days 1-21, and letrozole PO continuously on days 1-28. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive palbociclib PO QD for days 1-14 of course 1 and letrozole PO continuously on days 1-14. Patients then undergo biopsy. Patients then receive copanlisib (MTD) IV over 1 hour on days 1, 8, and 15 and letrozole PO continuously on days 1-28. Treatment with copanlisib and letrozole repeats every 28 days for up to 3.5 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 month. ;

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma
• Estrogen Receptor Positive
• HER2/Neu Negative
• Invasive Breast Carcinoma
• Multifocal Breast Carcinoma
• Postmenopausal
• Progesterone Receptor Positive
• Stage I Breast Cancer
• Stage IA Breast Cancer
• Stage IB Breast Cancer
• Stage II Breast Cancer
• Stage IIA Breast Cancer
• Stage IIB Breast Cancer
• Stage III Breast Cancer
• Stage IIIA Breast Cancer
• Stage IIIB Breast Cancer
• Stage IIIC Breast Cancer
• Stage IV Breast Cancer

• NCT number: NCT03128619
• Study type: Interventional
• Source: Jonsson Comprehensive Cancer Center
• Status: Terminated
• Phase: Phase 1
• Start date: August 2, 2017
• Completion date: March 31, 2022