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Breast NeoplasmsPhase 2NCT02756364

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

A Phase 2 study testing Fulvestrant and Sapanisertib in people with Breast Neoplasms, run by Calithera Biosciences, Inc at 53 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Neoplasms
What is being tested?
Fulvestrant and Sapanisertib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
141 participants
Where
53 sitesin 2 countries
Study dates
28 Jul 2016to 25 Nov 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 21Show fewer
  • 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.
  • Eastern cooperative oncology group (ECOG) performance status of 0 or 1.
  • 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.

Who cannot join

  • 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).
  • 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.

Trial locations and contacts

53 sites in 2 countries.

53 sites in 2 countries

United States30 sites

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

    Aurora, Colorado, 80045

  • Texas Oncology, P.A.

    Austin, Texas, 78745

  • CBCC Global Research 6501 Truxtun Avenue Bakersfield, CA

    Bakersfield, California, 93309

  • New Jersey Hematology & Oncology Associates

    Brick, New Jersey, 8724

  • Texas Oncology - Presbyterian Hospital

    Dallas, Texas, 75231

  • Texas Oncology, P.A.

    Dallas, Texas, 75246

  • Holy Cross Hospital- Bienes Cancer Center

    Fort Lauderdale, Florida, 33308

  • Ft. Wayne Medical Oncology and Hematology, Inc

    Fort Wayne, Indiana, 46804

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

    Fullerton, California, 92835

  • St. Mary'S Hospital Regional Cancer Center

    Grand Junction, Colorado, 81501

  • Comprehensive Cancer Centers of Nevada

    Henderson, Nevada, 89074

  • Memorial Healthcare System

    Hollywood, Florida, 33021

  • UCSD Moores Cancer Center

    La Jolla, California, 92037

  • Rocky mountain cancer centers LLP

    Lakewood, Colorado, 80228

  • Virginia Cancer Specialist PC

    Leesburg, Virginia, 20176

  • UCLA Hematology/Oncology David Geffen School of Medicine

    Los Angeles, California, 90095-7077

  • Texas Oncology- South Second Street

    McAllen, Texas, 78503

  • Southern Cancer Center, PC

    Mobile, Alabama, 36608

  • West Virginia University School of Medicine

    Morgantown, West Virginia, 26505

  • Northern Westchester Hospital Cancer Treatment & Wellness Center

    Mount Kisco, New York, 10549

  • North County Oncology

    Oceanside, California, 92056

  • Orlando Health Inc.

    Orlando, Florida, 33806

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Torrance Health Association

    Redondo Beach, California, 90277

  • Health Partners Institute Park Nicollet Frauenshuh Cancer Center

    Saint Louis Park, Minnesota, 55426

  • Cancer Care Centers of South Texas

    San Antonio, Texas, 78217

  • PHC-SLO Oncology and Hematology

    San Luis Obispo, California, 93401

  • Cancer Center of Santa Barbara With Sansum Clinic

    Santa Barbara, California, 93105

  • New England Cancer Specialists

    Scarborough, Maine, 04074

  • Texas Oncology,PA. Tyler TX, 75702

    Tyler, Texas, 75702

Other trials in United States

Spain23 sites

  • Complejo Hospitalario Universitario A Coruna

    A Coruña, 15006

  • Centro Oncologico de Galicia

    A Coruña, 15009

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic i Provincial

    Barcelona, 08036

  • Hospital De la Santa Creu i Sant Pau

    Barcelona, 08041

  • Hospital San Pedro de Alcantara

    Cáceres, 10003

  • Onkologikoa

    Donostia / San Sebastian, Guipuzcoa, 20014

  • Hospital Universitari Arnau de Vilanova de Lleida

    Lleida, 25198

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28009

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital Clinico San Carlos

    Madrid, 28040

  • Hospital Universitario Puerta del Hierro

    Majadahonda, Madrid, 28220

  • Hospital General Universitario Morales Messeguer

    Murcia, 30008

  • Hospital Clinico Universitario Virgen de la Arrixaca

    Murcia, 30120

  • Hospital Universitari Son Espases

    Palma de Mallorca, Balearic Islands, 07120

  • Hospital Son Llatzer

    Palma de Mallorca, Balearic Islands, 07198

  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31008

  • Hospital Universitario Sant Joan de Reus

    Reus, Tarragona, 43204

  • Hospital Universitario Virgen de la Macarena

    Seville, 41009

  • Consorci Sanitari de Terrassa

    Terrassa, Barcelona, 08827

  • Fundacion Instituto Valenciano de Oncologia

    Valencia, 46009

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

About this study

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

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.

Read the 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).

Being tested
Fulvestrant, Sapanisertib
Keywords
Drug Therapy
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FulvestrantDrug

    Fulvestrant IM injection.

  • SapanisertibDrug

    Also called MLN0128

    Sapanisertib capsule.

Study groups in NCT02756364
Study groupRoleWhat they receive
Fulvestrant 500 mgActive comparatorFulvestrant 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).
Receives: Drug: Fulvestrant
Fulvestrant 500 mg + Sapanisertib 4 mgExperimentalFulvestrant 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).
Receives: Drug: Fulvestrant; Drug: Sapanisertib
Fulvestrant 500 mg + Sapanisertib 30 mgExperimentalFulvestrant 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).
Receives: Drug: Fulvestrant; Drug: Sapanisertib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 40 months

Secondary outcomes (5)

  1. Overall Survival (OS)

    OS was defined as the time from the date of randomization to the date of death.

    Measured: Up to 164 weeks

  2. 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.

    Measured: Up to 40 months

  3. 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.

    Measured: Up to 40 months

  4. 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.

    Measured: Up to 40 months

  5. 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.

    Measured: Up to 164 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2016 (estimated)
  2. Study start28 Jul 2016
  3. Primary completion25 Nov 2019
  4. Study completion25 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
141 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02756364
Sponsor's protocol ID
C31006
Other IDs
2015-003612-20, U1111-1174-2165, 2015
Status last verified
Feb 2023
First submitted
28 Apr 2016
Last updated
8 Feb 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fulvestrant and Sapanisertib in people with Breast Neoplasms, run by Calithera Biosciences, Inc at 53 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: Up to 40 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02756364.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.

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