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

NCT02756364 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: C310062015-003612-20U1111-1174-2165
• Study Type: interventional
• Target: 141
• Locations: 2 countries
• Sites: 53

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.

Conditions

Breast Neoplasms

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  Up to 40 months

Secondary Outcomes (5)

• Overall Survival (OS)

  Up to 164 weeks

• Time to Progression (TTP)

  Up to 40 months

• Objective Response Rate (ORR)

  Up to 40 months

• Clinical Benefit Rate (CBR)

  Up to 40 months

• Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)

  Up to 164 weeks

Study Arms (3)

Fulvestrant 500 mg

ACTIVE COMPARATOR

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).

Drug: Fulvestrant

Fulvestrant 500 mg + Sapanisertib 4 mg

EXPERIMENTAL

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).

Drug: Fulvestrant; Drug: Sapanisertib

Fulvestrant 500 mg + Sapanisertib 30 mg

EXPERIMENTAL

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).

Drug: Fulvestrant; Drug: Sapanisertib

Interventions

Fulvestrant DRUG

Fulvestrant IM injection.

Fulvestrant 500 mg; Fulvestrant 500 mg + Sapanisertib 30 mg; Fulvestrant 500 mg + Sapanisertib 4 mg

Sapanisertib DRUG

Sapanisertib capsule.

Also known as: MLN0128

Fulvestrant 500 mg + Sapanisertib 30 mg; Fulvestrant 500 mg + Sapanisertib 4 mg

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Postmenopausal females.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female participants aged 18 years or older who are postmenopausal.
• Histologically proven diagnosis of breast cancer with evidence of metastatic disease or locoregional recurrence.
• Histological confirmation and documentation of estrogen receptor (ER)-positive status (≥1% positive stained cells).
• 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.
• 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.
• Progressive Disease (PD) during prior aromatase inhibitor (AI) therapy.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Calithera Biosciences, Inc: lead

Study Sites (53)

Southern Cancer Center, PC

Mobile, Alabama, 36608, United States

Location

CBCC Global Research 6501 Truxtun Avenue Bakersfield, CA

Bakersfield, California, 93309, United States

Location

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

Fullerton, California, 92835, United States

Location

UCSD Moores Cancer Center

La Jolla, California, 92037, United States

Location

UCLA Hematology/Oncology David Geffen School of Medicine

Los Angeles, California, 90095-7077, United States

Location

North County Oncology

Oceanside, California, 92056, United States

Location

Torrance Health Association

Redondo Beach, California, 90277, United States

Location

PHC-SLO Oncology and Hematology

San Luis Obispo, California, 93401, United States

Location

Cancer Center of Santa Barbara With Sansum Clinic

Santa Barbara, California, 93105, United States

Location

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

Aurora, Colorado, 80045, United States

Location

St. Mary'S Hospital Regional Cancer Center

Grand Junction, Colorado, 81501, United States

Location

Rocky mountain cancer centers LLP

Lakewood, Colorado, 80228, United States

Location

Holy Cross Hospital- Bienes Cancer Center

Fort Lauderdale, Florida, 33308, United States

Location

Memorial Healthcare System

Hollywood, Florida, 33021, United States

Location

Orlando Health Inc.

Orlando, Florida, 33806, United States

Location

Ft. Wayne Medical Oncology and Hematology, Inc

Fort Wayne, Indiana, 46804, United States

Location

New England Cancer Specialists

Scarborough, Maine, 04074, United States

Location

Health Partners Institute Park Nicollet Frauenshuh Cancer Center

Saint Louis Park, Minnesota, 55426, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89074, United States

Location

New Jersey Hematology & Oncology Associates

Brick, New Jersey, 8724, United States

Location

Northern Westchester Hospital Cancer Treatment & Wellness Center

Mount Kisco, New York, 10549, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Texas Oncology, P.A.

Austin, Texas, 78745, United States

Location

Texas Oncology - Presbyterian Hospital

Dallas, Texas, 75231, United States

Location

Texas Oncology, P.A.

Dallas, Texas, 75246, United States

Location

Texas Oncology- South Second Street

McAllen, Texas, 78503, United States

Location

Cancer Care Centers of South Texas

San Antonio, Texas, 78217, United States

Location

Texas Oncology,PA. Tyler TX, 75702

Tyler, Texas, 75702, United States

Location

Virginia Cancer Specialist PC

Leesburg, Virginia, 20176, United States

Location

West Virginia University School of Medicine

Morgantown, West Virginia, 26505, United States

Location

Hospital Universitari Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, Balearic Islands, 07198, Spain

Location

Consorci Sanitari de Terrassa

Terrassa, Barcelona, 08827, Spain

Location

Onkologikoa

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Hospital Universitario Puerta del Hierro

Majadahonda, Madrid, 28220, Spain

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario Sant Joan de Reus

Reus, Tarragona, 43204, Spain

Location

Complejo Hospitalario Universitario A Coruna

A Coruña, 15006, Spain

Location

Centro Oncologico de Galicia

A Coruña, 15009, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Hospital De la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital San Pedro de Alcantara

Cáceres, 10003, Spain

Location

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, 25198, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28009, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital General Universitario Morales Messeguer

Murcia, 30008, Spain

Location

Hospital Clinico Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Hospital Universitario Virgen de la Macarena

Seville, 41009, Spain

Location

Fundacion Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant; sapanisertib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue 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

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: April 28, 2016
• First Posted: April 29, 2016
• Study Start: July 28, 2016
• Primary Completion: November 25, 2019
• Study Completion: November 25, 2019
• Last Updated: February 8, 2023
• Results First Posted: December 19, 2020

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

ES (23); US (30)