Sapanisertib in Combination With Fulvestrant in Women With Advanced or Metastatic Breast Cancer After Aromatase Inhibitor Therapy

NCT ID: NCT02756364

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 141 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-28
• Study Completion Date: 2019-11-25

Brief Summary

The primary purpose of this study is to compare the progression free survival (PFS) of participants treated with the combination of fulvestrant plus daily sapanisertib and fulvestrant plus weekly sapanisertib versus participants treated with single-agent fulvestrant.

Detailed Description

The drug being tested in this study is called sapanisertib. Sapanisertib is being tested to treat postmenopausal women with advanced or metastatic estrogen receptor (ER) positive, human epidermal growth factor receptor-2 (HER2) negative breast cancer that has progressed during or after aromatase inhibitor (AI) therapy. This study will evaluate the efficacy and safety of combination of fulvestrant + daily sapanisertib and fulvestrant + weekly sapanisertib compared with fulvestrant alone.

The study will enroll approximately 153 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• Fulvestrant 500 mg
• Fulvestrant 500 mg + Sapanisertib 4 mg
• Fulvestrant 500 mg + Sapanisertib 30 mg

All participants will receive either fulvestrant 500 mg intramuscularly (IM), fulvestrant 500 mg + sapanisertib 4 mg daily or fulvestrant 500 mg + sapanisertib 30 mg weekly.

This multicenter trial will be conducted Spain and the USA. Participants will make multiple visits to the clinic, and end of treatment (EOT) visit which will occur 30 to 40 days after receiving their last dose of study drug or before the start of any subsequent anticancer therapy. After EOT, participants will be followed for progression free survival (PFS) and overall survival (OS).

Conditions

Breast Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fulvestrant 500 mg

Fulvestrant 500 mg, intramuscularly (IM), once on Days 1 and 15 in Cycle 1, and then on Day 1 of each subsequent 28-day cycle until progressive disease, unacceptable toxicity, or withdrawal of consent (Median duration of treatment was 16.0 weeks).

Group Type: ACTIVE_COMPARATOR

Fulvestrant

Intervention Type: DRUG

Fulvestrant IM injection.

Fulvestrant 500 mg + Sapanisertib 4 mg

Fulvestrant 500 mg, IM, once on Days 1 and 15 in Cycle 1, and then on Day 1 of each subsequent 28-day cycle along with the sapanisertib 4 mg, capsules, orally, once daily in each 28-day treatment cycle until progressive disease, unacceptable toxicity, or withdrawal of consent (Median duration of treatment was 20.1 and 20.3 weeks for fulvestrant and sapanisertib respectively).

Group Type: EXPERIMENTAL

Fulvestrant

Intervention Type: DRUG

Fulvestrant IM injection.

Sapanisertib

Intervention Type: DRUG

Sapanisertib capsule.

Fulvestrant 500 mg + Sapanisertib 30 mg

Fulvestrant 500 mg, IM, once on Days 1 and 15 in Cycle 1, and then on Day 1 of each subsequent 28-day cycle along with sapanisertib 30 mg, capsule, orally, once weekly in each 28-day treatment cycle until progressive disease, unacceptable toxicity, or withdrawal of consent (Median duration of treatment was 17.0 weeks for fulvestrant and sapanisertib, each).

Group Type: EXPERIMENTAL

Fulvestrant

Intervention Type: DRUG

Fulvestrant IM injection.

Sapanisertib

Intervention Type: DRUG

Sapanisertib capsule.

Interventions

Fulvestrant

Fulvestrant IM injection.

Intervention Type: DRUG

Sapanisertib

Sapanisertib capsule.

Intervention Type: DRUG

Other Intervention Names

MLN0128

Eligibility Criteria

Inclusion Criteria

1. Female participants aged 18 years or older who are postmenopausal.

2. Histologically proven diagnosis of breast cancer with evidence of metastatic disease or locoregional recurrence.

3. Histological confirmation and documentation of estrogen receptor (ER)-positive status (≥1% positive stained cells).

4. Histological or cytological confirmation and documentation of human epidermal growth factor receptor-2 (HER2)-negative status by local laboratory testing using criteria in the American Society of Oncology (ASCO)/College of American Pathologists (CAP) Clinical Practice Guideline update.

5. Measurable disease defined as either of the following:

• At least 1 extra-osseous lesion that could be accurately measured in at least 1 dimension.
• The lesion must have measured ≥20 mm with conventional imaging techniques or ≥10 mm with spiral CT or MRI. Lymph nodes must be ≥1.5 cm in the short axis to be considered measurable.
• Bone lesions (lytic or mixed [lytic plus sclerotic]) in the absence of measurable disease as defined above. Note: Participants with sclerotic/osteoblastic bone lesions only, in the absence of measurable disease, were not eligible.

6. Progressive Disease (PD) during prior aromatase inhibitor (AI) therapy.

7. Have a history of brain metastasis provided that all of the following criteria are met:

• Brain metastases have been treated.
• No evidence of PD for ≥3 months before the first dose of study drug.
• No hemorrhage after treatment.
• Off dexamethasone treatment for ≥4 weeks before the first dose of study drug.
• No ongoing requirement for dexamethasone or anti-epileptic drugs.

8. Eastern cooperative oncology group (ECOG) performance status of 0 or 1.

9. Clinical laboratory values as specified below within 4 weeks before the first dose of study drug:

• Bone marrow reserve consistent with absolute neutrophil count (ANC) ≥1.5*10^9/L; platelet count ≥100*10^9/L; hemoglobin (Hgb) ≥9 g/dL.
• Total bilirubin ≤1.5*the upper limit of the normal range (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5*ULN (≤5*ULN if liver metastases are present).
• Creatinine clearance ≥40 mL/min based on Cockcroft-Gault estimate or based on a 12- or 24-hour urine collection.
• Fasting serum glucose ≤130 mg/dL and fasting triglycerides ≤300 mg/dL.

Exclusion Criteria

1. Prior therapy with mechanistic target of rapamycin (mTOR), phosphoinositide-3-kinase (PI3K), or dual PI3K-mTOR inhibitors, serine/threonine-specific protein kinase (AKT) inhibitors, or fulvestrant.

2. Prior treatment with >1 line of chemotherapy for metastatic breast cancer or for locoregional recurrence that was not amenable to resection or radiation therapy with curative intent.

3. Experienced PD on >2 endocrine therapies for metastatic breast cancer or for locoregional recurrence that was not amenable to resection or radiation therapy with curative intent.

4. Life-threatening metastatic visceral disease (defined as extensive hepatic involvement or symptomatic pulmonary lymphangitic spread).

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Calithera Biosciences, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Southern Cancer Center, PC

Mobile, Alabama, United States

CBCC Global Research 6501 Truxtun Avenue Bakersfield, CA

Bakersfield, California, United States

St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare

Fullerton, California, United States

UCSD Moores Cancer Center

La Jolla, California, United States

UCLA Hematology/Oncology David Geffen School of Medicine

Los Angeles, California, United States

North County Oncology

Oceanside, California, United States

Torrance Health Association

Redondo Beach, California, United States

PHC-SLO Oncology and Hematology

San Luis Obispo, California, United States

Cancer Center of Santa Barbara With Sansum Clinic

Santa Barbara, California, United States

University of Colorado Cancer Center-Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, United States

St. Mary'S Hospital Regional Cancer Center

Grand Junction, Colorado, United States

Rocky mountain cancer centers LLP

Lakewood, Colorado, United States

Holy Cross Hospital- Bienes Cancer Center

Fort Lauderdale, Florida, United States

Memorial Healthcare System

Hollywood, Florida, United States

Orlando Health Inc.

Orlando, Florida, United States

Ft. Wayne Medical Oncology and Hematology, Inc

Fort Wayne, Indiana, United States

New England Cancer Specialists

Scarborough, Maine, United States

Health Partners Institute Park Nicollet Frauenshuh Cancer Center

Saint Louis Park, Minnesota, United States

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States

New Jersey Hematology & Oncology Associates

Brick, New Jersey, United States

Northern Westchester Hospital Cancer Treatment & Wellness Center

Mount Kisco, New York, United States

Oregon Health and Science University

Portland, Oregon, United States

Texas Oncology, P.A.

Austin, Texas, United States

Texas Oncology - Presbyterian Hospital

Dallas, Texas, United States

Texas Oncology, P.A.

Dallas, Texas, United States

Texas Oncology- South Second Street

McAllen, Texas, United States

Cancer Care Centers of South Texas

San Antonio, Texas, United States

Texas Oncology,PA. Tyler TX, 75702

Tyler, Texas, United States

Virginia Cancer Specialist PC

Leesburg, Virginia, United States

West Virginia University School of Medicine

Morgantown, West Virginia, United States

Hospital Universitari Son Espases

Palma de Mallorca, Balearic Islands, Spain

Hospital Son Llatzer

Palma de Mallorca, Balearic Islands, Spain

Consorci Sanitari de Terrassa

Terrassa, Barcelona, Spain

Onkologikoa

Donostia / San Sebastian, Guipuzcoa, Spain

Hospital Universitario Puerta del Hierro

Majadahonda, Madrid, Spain

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Hospital Universitario Sant Joan de Reus

Reus, Tarragona, Spain

Complejo Hospitalario Universitario A Coruna

A Coruña, , Spain

Centro Oncologico de Galicia

A Coruña, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clinic i Provincial

Barcelona, , Spain

Hospital De la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital San Pedro de Alcantara

Cáceres, , Spain

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, , Spain

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital General Universitario Morales Messeguer

Murcia, , Spain

Hospital Clinico Universitario Virgen de la Arrixaca

Murcia, , Spain

Hospital Universitario Virgen de la Macarena

Seville, , Spain

Fundacion Instituto Valenciano de Oncologia

Valencia, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Countries

United States; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-003612-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1174-2165

Identifier Type: REGISTRY

Identifier Source: secondary_id

C31006

Identifier Type: -

Identifier Source: org_study_id