TAK-228 and TAK-117 Followed by Cisplatin and Nab Paclitaxel for Metastatic Triple Negative Breast Cancer

NCT03193853 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 017- 113Baylor 017-113
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates efficacy of TAK- 228 and TAK- 117 followed by cisplatin and nab paclitaxel in patients with metastatic triple negative breast cancer.

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Efficacy (Objective Response Rate)

  To assess the objective response rate associated with sequential treatment of the oral combination TAK 228 and 117 followed by nab-paclitaxel plus cisplatin in metastatic TNBC. Objective response is measured as prolonged clinical benefit; clinical benefit is defined as progression free survival on study therapy for at least 6 months.

  Through study completion, up to 2 years 8 months

Secondary Outcomes (3)

• Efficacy (Duration of Response)

  Through study completion, up to 2 years 8 months

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0".

  For up to 30 days following last dose, approximately 7 months

• Number of Treatment-Emergent Adverse Events (Safety and Tolerability)

  For up to 30 days following last dose, approximately 7 months

Study Arms (1)

Tak + cisplatin and nab paclitaxel

EXPERIMENTAL

Patients with metastatic TNBC who meet the enrollment criteria will receive TAK-228 and TAK-117 until disease progression followed by nab paclitaxel plus cisplatin for six cycles. Patients who did not progress may continue nab paclitaxel under treating physicians discretion.

Drug: Tak-228 & Tak-117; Drug: Cisplatin & Nab Paclitaxel

Interventions

Tak-228 & Tak-117 DRUG

Patients will receive 4mg oral TAK-228 and 200mg TAK-117 tablets until disease progression.

Tak + cisplatin and nab paclitaxel

Cisplatin & Nab Paclitaxel DRUG

following Tak-228 \& Tak-117 standard nab paclitaxel 175-220 mg/m2 plus cisplatin 60-75 mg/m2 infusion for six cycles. Patients who did not progress may continue nab paclitaxel under treating physicians discretion

Tak + cisplatin and nab paclitaxel

Eligibility Criteria

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

You may qualify if:

• Female patients 18 years or older.
• Have a diagnosis of metastatic TNBC previously treated with standard anthracycline, cyclophosphamide, and taxane chemotherapy, unless there was a contraindication to doxorubicin, in which case prior treatment with this agent is not required.
• Have not received more than 3 prior chemotherapy regimens for metastatic disease. Prior platinum and/or taxane therapy in the adjuvant or metastatic setting is permitted.
• Androgen receptor-negative (less than 10% positive nuclei) on standard IHC performed at the local pathology laboratory.
• Have locoregional (eg, breast, chest wall, regional lymphatic) or pulmonary or hepatic metastatic disease that is amenable to core needle biopsy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (See Appendix I)
• 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 methods of contraception and 1 additional effective (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer as mandated by local labeling \[eg, USPI, SmPC, etc,\]) after the last dose of study drug, OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
• Screening clinical laboratory values as specified below:
• Bone marrow reserve consistent with: absolute neutrophil count (ANC) ≥ 1.5 x 10\^9; platelet count ≥ 100 x 10\^9; hemoglobin ≥ 9 g/dL without transfusion within 1 week preceding study drug administration
• Hepatic: total bilirubin ≤ 1.5 x upper limit of normal (ULN), transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present);
• Renal: creatinine clearance ≥60 mL/min based either on cockroft-Gault estimate or based on urine collection (12 or 24 hour);

You may not qualify if:

• Leptomeningeal disease that is symptomatic or cytology-proven.
• Other clinically significant co-morbidities, 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 treatment according to this protocol.
• Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug, 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.
• Breast feeding or pregnant.
• Treatment with any investigational products within 30 days before the first dose of study drug
• Previous treatment with PI3K, AKT, dual PI3K/mTOR inhibitors, TORC1/2 inhibitors or TORC1 inhibitors.
• Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of PIKTOR. In addition, patients with enteric stomata are also excluded.
• History of any of the following within the last 6 months before administration of the first dose of the drug:
• 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 or ventricular tachycardia)
• Placement of a pacemaker for control of rhythm

Sponsors & Collaborators

• Joyce O'Shaughnessy: lead
• Takeda: collaborator

Study Sites (1)

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Related Publications (1)

• Lang JD, Nguyen TVV, Levin MK, Blas PE, Williams HL, Rodriguez ESR, Briones N, Mueller C, Selleck W, Moore S, Zismann VL, Hendricks WPD, Espina V, O'Shaughnessy J. Pilot clinical trial and phenotypic analysis in chemotherapy-pretreated, metastatic triple-negative breast cancer patients treated with oral TAK-228 and TAK-117 (PIKTOR) to increase DNA damage repair deficiency followed by cisplatin and nab paclitaxel. Biomark Res. 2023 Jul 25;11(1):73. doi: 10.1186/s40364-023-00511-7.

  PMID: 37491309 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

sapanisertib; serabelisib; Cisplatin; Taxes

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Joyce O'Shaughnessy
• Organization: Baylor Scott and White Health

joyce.oshaughnessy@usoncology.com

214-818-8472

Study Officials

• Joyce O'Shaughnessy, MD

  Baylor Scott & White Research Institute

  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: SPONSOR INVESTIGATOR
• PI Title: Medical Oncologist/Medical Director

Model Details: Patients with metastatic TNBC who meet the enrollment criteria will receive TAK-228 and TAK-117 until disease progression followed by nab paclitaxel plus cisplatin.

Study Record Dates

• First Submitted: June 9, 2017
• First Posted: June 21, 2017
• Study Start: July 18, 2017
• Primary Completion: March 17, 2020
• Study Completion: December 1, 2022
• Last Updated: August 7, 2023
• Results First Posted: May 9, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)