Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Cisplatin

Serabelisib

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

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.

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

Tak-228 & Tak-117

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

Cisplatin & Nab Paclitaxel

Joyce O'Shaughnessy, MD

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

Seventy to eighty percent of breast cancers have a gene expression profile which is characterized by homologous recombination deficiency (HRD) and high proliferation. HRD leads to errors in DNA pathway \[non -homologous end joining (NHEJ)\] that repair DNA-breaks, a process required for metastatic triple negative breast cancer (TNBC) survival. The hypothesis of this pilot trial is that administration of the oral combination of TAK-228 and TAK-117 (PIKTOR) will inhibit NHEJ in metastatic TNBC, leading at the time of disease progression to metastases that are HR-deficient and sensitive to cisplatin plus nab paclitaxel therapy.

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.

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

Phase II Clinical Trial of Treatment With TAK-228 and TAK-117 to Inhibit Homologous Recombination (HR) Followed by Cisplatin and Nab Paclitaxel in Patients With Chemotherapy-pretreated Metastatic Triple Negative Breast Cancer

The Investigators will share de-identified data with Takeda for information/publication purposes

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.

To assess duration of response associated with sequential treatment of the oral combination Tak 228 and 117 followed by nab-paclitaxel plus cisplatin. Duration of response is measured as prolonged clinical benefit; clinical benefit is defines as progression free survival on study therapy for at least 6 months.

To assess safety associated with sequential treatment of the oral combination Tak 228 and 117 followed by nab-paclitaxel plus cisplatin

To assess safety associated with sequential treatment of the oral combination TAK 228 and TAK 117 followed by nab-paclitaxel plus cisplatin per CTCAE v4.0 criteria.

Takeda

Joyce O'Shaughnessy

Medical Oncologist/Medical Director

All AEs are recorded for up to 30 days following the last dose of study treatment, approximately 7 months

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.

Tak-228 \& Tak-117: Patients will receive oral TAK-228 and TAK-117 tablets until disease progression.

Cisplatin \& Nab Paclitaxel: following Tak-228 \& Tak-117 standard nab paclitaxel plus cisplatin infusion for six cycles. Patients who did not progress may continue nab paclitaxel under treating physicians discretion

Tak + Cisplatin and Nab Paclitaxel

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

All participants who received at least one dose of treatment.

Efficacy (Objective Response Rate)

Efficacy (Duration of Response)

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

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

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.

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

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

Spots Global Cancer Trial Database for cisplatin & nab paclitaxel