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

Breast Neoplasms Clinical Trial

Official title:

An Open-Label Phase 2 Study of MLN0128 (A TORC1/2 Inhibitor) in Combination With Fulvestrant in Women With ER-Positive/HER2-Negative Advanced or Metastatic Breast Cancer That Has Progressed During or After Aromatase Inhibitor Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02756364
• Other study ID #: C31006
• Secondary ID: 2015-003612-20U1
• Status: Completed
• Phase: Phase 2
• Start date: July 28, 2016
• Est. completion date: November 25, 2019

Study information

• Verified date: February 2023
• Source: Calithera Biosciences, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 141
• Est. completion date: November 25, 2019
• Est. primary completion date: November 25, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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).

5. Poorly controlled diabetes mellitus defined as hemoglobin A1c (glycosylated hemoglobin; HbA1c) >7%; participants with a history of transient glucose intolerance due to corticosteroid administration may be eligible if all other inclusion/exclusion criteria are met.

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Fulvestrant
Fulvestrant IM injection.
• Sapanisertib
Sapanisertib capsule.

Locations

Country	Name	City	State
Spain	Centro Oncologico de Galicia	A Coruna
Spain	Complejo Hospitalario Universitario A Coruna	A Coruna
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital De la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital San Pedro de Alcantara	Caceres
Spain	Hospital Universitari Arnau de Vilanova de Lleida	Lleida
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Puerta del Hierro	Majadahonda	Madrid
Spain	Hospital Clinico Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital General Universitario Morales Messeguer	Murcia
Spain	Hospital Son Llatzer	Palma de Mallorca	Islas Baleares
Spain	Hospital Universitari Son Espases	Palma de Mallorca	Islas Baleares
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario Sant Joan de Reus	Reus	Tarragona
Spain	Onkologikoa	San Sebastian	Guipuzcoa
Spain	Hospital Universitario Virgen de la Macarena	Sevilla
Spain	Consorci Sanitari de Terrassa	Terrassa	Barcelona
Spain	Fundacion Instituto Valenciano de Oncologia	Valencia
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
United States	University of Colorado Cancer Center-Anschutz Cancer Pavilion (ACP)	Aurora	Colorado
United States	Texas Oncology, P.A.	Austin	Texas
United States	CBCC Global Research 6501 Truxtun Avenue Bakersfield, CA	Bakersfield	California
United States	New Jersey Hematology & Oncology Associates	Brick	New Jersey
United States	Texas Oncology - Presbyterian Hospital	Dallas	Texas
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Holy Cross Hospital- Bienes Cancer Center	Fort Lauderdale	Florida
United States	Ft. Wayne Medical Oncology and Hematology, Inc	Fort Wayne	Indiana
United States	St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare	Fullerton	California
United States	St. Mary'S Hospital Regional Cancer Center	Grand Junction	Colorado
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	Memorial Healthcare System	Hollywood	Florida
United States	UCSD Moores Cancer Center	La Jolla	California
United States	Rocky mountain cancer centers LLP	Lakewood	Colorado
United States	Virginia Cancer Specialist PC	Leesburg	Virginia
United States	UCLA Hematology/Oncology David Geffen School of Medicine	Los Angeles	California
United States	Texas Oncology- South Second Street	McAllen	Texas
United States	Southern Cancer Center, PC	Mobile	Alabama
United States	West Virginia University School of Medicine	Morgantown	West Virginia
United States	Northern Westchester Hospital Cancer Treatment & Wellness Center	Mount Kisco	New York
United States	North County Oncology	Oceanside	California
United States	Orlando Health Inc.	Orlando	Florida
United States	Oregon Health and Science University	Portland	Oregon
United States	Torrance Health Association	Redondo Beach	California
United States	Health Partners Institute Park Nicollet Frauenshuh Cancer Center	Saint Louis Park	Minnesota
United States	Cancer Care Centers of South Texas	San Antonio	Texas
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	New England Cancer Specialists	Scarborough	Maine
United States	Texas Oncology,PA. Tyler TX, 75702	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Calithera Biosciences, Inc

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	OS was defined as the time from the date of randomization to the date of death.	Up to 164 weeks
Secondary	Time to Progression (TTP)	TTP was defined as the time from the date of randomization to the date of first documentation of progression. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of the 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	Objective Response Rate (ORR)	ORR was defined as the percentage of participants who achieve a best response of complete response (CR) or partial response (PR) according to RECIST v1.1 criteria. CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.	Up to 40 months
Secondary	Clinical Benefit Rate (CBR)	CBR was defined as the percentage of participants who achieved a best response of CR, PR, or stable disease (SD) of any duration. CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.	Up to 40 months
Secondary	Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.	Up to 164 weeks