- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02988986
TAK-228 Plus Tamoxifen in Patients With ER-Positive, HER2-negative Breast Cancer (ANETT)
Open Label, Phase II Trial of Neoadjuvant TAK-228 Plus Tamoxifen in Patients With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Houston Methodist Hospital
-
Houston, Texas, United States, 77070
- Houston Methodist Hospital Willowbrook
-
Sugar Land, Texas, United States, 77479
- Houston Methodist Hospital Sugar Land
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient
- Agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of the study drugs.
Screening clinical laboratory values as specified below:
- Bone marrow reserve consistent with: absolute neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL (without transfusion) within 1 week preceding the administration of the study drugs;
- Hepatic status: Serum total bilirubin ≤ 1 x upper limit of normal (ULN; in the case of known Gilbert's syndrome, a higher serum total bilirubin [< 1.5 x ULN] is allowed), aspartate aminotransferase and alanine aminotransferase ≤ 1.5 x ULN, and alkaline phosphatase ≤ 1.5 x ULN;
- Renal status: Creatinine clearance ≥50 mL/min based on Cockcroft-Gault estimate or based on urine collection (12 or 24 hour);
- Metabolic status: HbA1c < 7.0%, fasting serum glucose ≤ 130 mg/dL, and fasting triglycerides ≤ 300 mg/dL.
- Ability to swallow oral medications.
- Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
- Negative serum pregnancy test within 7 days prior to the administration of the study drugs for female patients of childbearing potential.
- Patient must be accessible for treatment and follow-up.
- Patient must be willing to undergo breast biopsies as required by the study protocol.
Exclusion Criteria:
- 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.
- Poorly controlled diabetes mellitus (defined as HbA1c > 7%). Patients with a history of transient glucose intolerance due to corticosteroid administration may be enrolled in the study if all other inclusion criteria and none of the other exclusion criteria are met.
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
- Pulmonary embolism
Significant active cardiovascular or pulmonary disease including:
- Uncontrolled hypertension (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg). Use of antihypertensive agents to control hypertension before week 1, day 1 is allowed.
- Pulmonary hypertension
- Uncontrolled asthma or O2 saturation < 90% by arterial blood gas analysis or pulse oximetry on room air
- Significant valvular disease, severe regurgitation, or stenosis by imaging independent of symptom control with medical intervention or history of valve replacement
- Medically significant (symptomatic) bradycardia
- History of arrhythmia requiring an implantable cardiac defibrillator
- Baseline QTc prolongation (e.g., repeated demonstration of QTc interval > 480 milliseconds or history of congenital long QT syndrome or torsades de pointes)
- Treatment with strong inhibitors and/or inducers of CYP3A4, CYP2C9, or CYP2C19 within 7 days preceding the first dose of the study drugs.
- Patients receiving systemic corticosteroids (either IV or oral steroids, excluding inhalers or low-dose hormone replacement therapy) within 1 week before administration of the first dose of the study drugs.
- Daily or chronic use of a proton pump inhibitor (PPI) and/or having taken a PPI within 7 days before receiving the first dose of the study drugs.
- Patients unwilling or unable to comply with the study protocol.
- Patients previously treated with hormonal therapy (tamoxifen, AI) or PI3K, AKT, dual PI3K/mTOR, TORC1/2, or mTORC1 inhibitors.
- Patients who are currently being treated with cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) other than the trial therapy.
- Patients with hypersensitivity to mTOR inhibitors or tamoxifen.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: TAK-228 Plus Tamoxifen
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. |
MTORC1/2 inhibitor
Other Names:
Non-steroidal anti-estrogen
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ki67 Expression
Time Frame: Baseline to 6 weeks
|
Ki67 expression change from baseline to 6 weeks
|
Baseline to 6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Meeting Certain Preoperative Endocrine Prognostic Index (PEPI)
Time Frame: 16 weeks
|
Evaluate the number of participants meeting certain PEPI score after treatment with TAK-228 plus tamoxifen. PEPI score of 0 indicates low risk of disease recurrence (better outcome) PEPI score of 1-3 indicates intermediate risk of of disease recurrence (worse outcome) PEPI score of >4 indicates high risk of of disease recurrence (worst outcome) |
16 weeks
|
Number of Participants With Pathological Complete Response (pCR)
Time Frame: 16 weeks
|
Pathologic complete response was defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0 ypN0 or ypTis ypN0 in the current American Joint Committee on Cancer staging system).
|
16 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma Concentrations of TAK-228 Plus Tamoxifen
Time Frame: 16 weeks
|
Measure plasma concentrations of TAK-228 plus tamoxifen over time
|
16 weeks
|
Correlation Between Change in Ki67 Expression and pCR to TAK-228 Plus Tamoxifen
Time Frame: 16 weeks
|
Assess the 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
Time Frame: 16 weeks
|
Assess correlation between tumor mutational status and response to TAK-228 plus tamoxifen
|
16 weeks
|
Correlation Between Change in mTOR Expression and pCR to TAK-228 Plus Tamoxifen
Time Frame: 16 weeks
|
Assess the correlation between change in mTOR expression and pCR to TAK-228 plus tamoxifen
|
16 weeks
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Jenny C Chang, M.D., Houston Methodist Cancer Center
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Hormone Antagonists
- Bone Density Conservation Agents
- Estrogen Antagonists
- Selective Estrogen Receptor Modulators
- Estrogen Receptor Modulators
- Tamoxifen
Other Study ID Numbers
- Pro00016065
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Estrogen Receptor Positive Breast Cancer
-
Eisai Inc.CompletedBreast Cancer | Breast Neoplasms | Cancer, Breast | Breast Cancer Female | Estrogen Receptor Positive Tumor | Breast Adenocarcinoma | ER Positive | Estrogen-receptor Positive Breast CancerFrance, United Kingdom, United States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Estrogen Receptor-negative Breast Cancer | Estrogen Receptor-positive Breast Cancer | Progesterone Receptor-negative Breast Cancer | Progesterone Receptor-positive Breast...United States
-
National Cancer Institute (NCI)TerminatedStage IV Breast Cancer | Recurrent Breast Carcinoma | Estrogen Receptor Negative | Estrogen Receptor Positive | HER2/Neu Positive | Progesterone Receptor Negative | Progesterone Receptor PositiveUnited States
-
Syndax PharmaceuticalsCompletedBreast Cancer | ER+ Breast Cancer | Estrogen Receptor-Positive Breast Cancer | Breast Cancer, Estrogen Receptor-PositiveUnited States, Czechia, Canada, Hungary, Russian Federation
-
Vanderbilt-Ingram Cancer CenterNational Cancer Institute (NCI); Genentech, Inc.; Translational Breast Cancer... and other collaboratorsTerminatedStage IV Breast Cancer | Estrogen Receptor Negative | Estrogen Receptor Positive | HER2/Neu Negative | Progesterone Receptor Negative | Progesterone Receptor Positive | Triple-Negative Breast CarcinomaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI); Merck Sharp & Dohme LLCCompletedStage IV Breast Cancer | Estrogen Receptor Negative | Estrogen Receptor Positive | HER2/Neu Negative | Progesterone Receptor Negative | Progesterone Receptor Positive | Triple-Negative Breast CarcinomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedInflammatory Breast Cancer | Male Breast Cancer | Stage IV Breast Cancer | Stage IIIB Breast Cancer | Estrogen Receptor-negative Breast Cancer | Estrogen Receptor-positive Breast Cancer | Progesterone Receptor-negative Breast Cancer | Progesterone Receptor-positive Breast CancerUnited States
-
Istituto Scientifico Romagnolo per lo Studio e...TerminatedEstrogen Receptor Positive Breast Cancer | Androgen Receptor Gene Overexpression | Progesterone Receptor Positive Tumor | Metastatic Breastcancer | Estrogen Receptor Negative Neoplasm | Progesterone Receptor Negative NeoplasmItaly
-
National Cancer Institute (NCI)TerminatedStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor Negative | Estrogen Receptor Positive | HER2/Neu Negative | HER2/Neu Positive | Progesterone Receptor Negative | Progesterone Receptor Positive and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Breast Carcinoma | Estrogen Receptor Negative | Estrogen Receptor Positive | HER2/Neu Negative | HER2/Neu Positive | Progesterone Receptor Negative | Progesterone Receptor Positive | Stage IIIC Breast Cancer AJCC v6 | Stage IV Breast Cancer AJCC v6 and v7United States, Puerto Rico
Clinical Trials on TAK-228
-
Calithera Biosciences, IncTerminatedAdvanced Nonhematological NeoplasmsKorea, Republic of, Japan, Taiwan
-
Bradley A. McGregor, MDCalithera Biosciences, IncActive, not recruitingRenal Cell CarcinomaUnited States
-
Calithera Biosciences, IncCompletedAdvanced Solid TumorsUnited States
-
M.D. Anderson Cancer CenterMillennium Pharmaceuticals, Inc.WithdrawnMalignant Neoplasms of Female Genital Organs | Malignant Neoplasms of Lip Oral Cavity and Pharynx | Malignant Neoplasms of Digestive Organs | Malignant Neoplasms of Male Genital Organs
-
National Cancer Institute (NCI)CompletedRefractory Pancreatic Neuroendocrine Carcinoma | Pancreatic Neuroendocrine Tumor G1 | Pancreatic Neuroendocrine Tumor G2United States
-
National Cancer Institute (NCI)CompletedRecurrent Lung Squamous Cell Carcinoma | Stage IV Lung Squamous Cell Carcinoma AJCC v7United States
-
National Cancer Institute (NCI)Active, not recruitingRecurrent Adult Acute Lymphoblastic Leukemia | B Acute Lymphoblastic Leukemia | Refractory Adult Acute Lymphoblastic Leukemia | B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative | B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 | T Acute Lymphoblastic LeukemiaUnited States
-
Millennium Pharmaceuticals, Inc.CompletedAdvanced Nonhematologic MalignanciesUnited States, Spain, United Kingdom
-
National Cancer Institute (NCI)TerminatedHigh Grade Sarcoma | Metastatic Leiomyosarcoma | Stage III Uterine Corpus Leiomyosarcoma AJCC v8 | Stage IV Uterine Corpus Leiomyosarcoma AJCC v8 | Unresectable Leiomyosarcoma | Myxofibrosarcoma | Metastatic Malignant Peripheral Nerve Sheath Tumor | Metastatic Synovial Sarcoma | Metastatic Undifferentiated... and other conditionsUnited States
-
National Cancer Institute (NCI)TerminatedGlioblastoma | GliosarcomaUnited States