TAK-228 Plus Tamoxifen in Patients With ER-Positive, HER2-negative Breast Cancer

NCT02988986 | Completed Phase 2 Results FDA Drug

• 1 other identifier: Pro00016065
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open label phase II clinical trial to determine the efficacy, toxicity, and safety of TAK-228 plus tamoxifen in patients with newly diagnosed ER-positive, HER2-negative breast cancer.

Conditions

Estrogen Receptor Positive Breast Cancer

Keywords

mTOR; Tamoxifen; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Ki67 Expression

  Ki67 expression change from baseline to 6 weeks

  Baseline to 6 weeks

Secondary Outcomes (2)

• Number of Participants Meeting Certain Preoperative Endocrine Prognostic Index (PEPI)

  16 weeks

• Number of Participants With Pathological Complete Response (pCR)

  16 weeks

Other Outcomes (4)

• Plasma Concentrations of TAK-228 Plus Tamoxifen

  16 weeks

• Correlation Between Change in Ki67 Expression and pCR to TAK-228 Plus Tamoxifen

  16 weeks

• Correlation Between Tumor Mutational Status and Response to TAK-228 Plus Tamoxifen

  16 weeks

Study Arms (1)

TAK-228 Plus Tamoxifen

EXPERIMENTAL

TAK-228 will be orally administered at 30 mg weekly for 16 weeks. Tamoxifen will be orally administered at 20 mg daily for 16 weeks.

Drug: TAK-228; Drug: Tamoxifen

Interventions

TAK-228 DRUG

MTORC1/2 inhibitor

Also known as: INK128, MLN0128

TAK-228 Plus Tamoxifen

Tamoxifen DRUG

Non-steroidal anti-estrogen

Also known as: Apo-Tamox, Gen-Tamoxifen, Nolvadex, Novo-Tamoxifen

TAK-228 Plus Tamoxifen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male ≥ 18 years of age.
• Newly diagnosed ER-positive, HER2-negative breast cancer. ER-positive is defined as ≥ 1% immunohistochemical (IHC) staining of any intensity. HER2 test result is negative if a single test (or both tests) performed show:
• IHC 1+ or 0
• In situ hybridization negative based on:
• Single-probe average HER2 copy number \< 4.0 signals/cell
• Dual-probe HER2/CEP17 ratio \< 2 with an average HER2 copy number \< 4.0 signals/cell.
• Patients with stage II-III breast cancer are eligible if they are deemed appropriate for neoadjuvant endocrine therapy by the referring or treating medical oncologist. Patients with stage I disease are eligible if they are deemed borderline candidates for breast conservation and the treating surgeon recommends preoperative therapy to increase the chances of breast conservation.
• Eastern Cooperative Oncology Group performance status and/or other performance status of ≤ 1.
• Female patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 1 effective method of contraception and 1 additional effective (barrier) method, at the same time, from the time of signing the ICF through 90 days (or longer, as mandated by local labeling \[e.g., United Surgical Partners International, summary of product characteristics, etc.\] after the last dose of the study drugs, OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient (periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condom should not be used together).
• Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
• Agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of the study drugs, OR

You may not qualify if:

• Any patient with metastatic disease.
• Other clinically significant comorbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study.
• Known human immunodeficiency virus infection.
• Known hepatitis B surface antigen-positive or known or suspected active hepatitis C infection.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of the protocol-specified treatment.
• Diagnosed or treated for another malignancy within 2 years before administration of the first dose of the study drugs or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Breastfeeding or pregnant.
• Manifestations of malabsorption due to prior gastrointestinal surgery, gastrointestinal disease, or an unknown reason that may alter the absorption of TAK-228. Patients with enteric stomata are also excluded.
• Treatment with any investigational products within 2 weeks before administration of the first dose of the study drugs.
• History of any of the following within the last 6 months before administration of the first dose of the study drugs:
• Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
• Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures
• Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, and ventricular tachycardia)
• Placement of a pacemaker for control of rhythm
• New York Heart Association Class III or IV heart failure

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (3)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital Willowbrook

Houston, Texas, 77070, United States

Location

Houston Methodist Hospital Sugar Land

Sugar Land, Texas, 77479, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

sapanisertib; Tamoxifen

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Jenny Chang, Director of Houston Methodist Cancer Center
• Organization: Houston Methodist Hospital

jcchang@houstonmethodist.org

713-441-0681

Study Officials

• Jenny C Chang, M.D.

  Houston Methodist Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Houston Methodist Cancer Center Director

Study Record Dates

• First Submitted: November 30, 2016
• First Posted: December 12, 2016
• Study Start: April 24, 2017
• Primary Completion: February 1, 2019
• Study Completion: March 30, 2019
• Last Updated: September 22, 2021
• Results First Posted: July 27, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: From study end (3/30/2019) for 5 years.
• Access Criteria: Data and materials on human subjects will be shared with other eligible investigators through appropriate means in accordance with the NIH policy on Sharing Research Data (NIH Guide, February 26, 2003). Data will be also shared with the funding agency and regulatory agencies as required. Data will be shared with other investigators within the limits of HIPAA and other patient confidentiality requirements. This will generally require removal of all patient identifiers for all source documents and the use of arbitrarily assigned one-way identifiers. In some cases, requestors will be asked to sign a formal data sharing agreement that will provide for a commitment to use data only for research purposes and not to identify individuals, keep the data secure, and destroy or return data after analyses are complete. Prior approval will be obtained from collaborating investigators, research sponsors, and/or other stake-holders before sharing if proprietary information or products are involved.

Locations

US (3)