Ovarian Cancer

Breast Cancer

Olaparib twice daily (starting dose 50 mg) and BKM120 once daily (starting dose 40 mg). Both drugs are given orally.

BKM120 and Olaparib

Olaparib twice daily (starting dose 100 mg) and BYL719 once daily (starting dose 250 mg). Both drugs are given orally.

BYL719 and Olaparib

Massachusetts General Hospital

Beth Israel Deaconess Medical Center

Dana-Farber Cancer Institute

Memorial Sloan-Kettering Cancer Center

MD Anderson Cancer Center

Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent Triple Negative Breast Cancer or High Grade Serous Ovarian Cancer

To determine the maximally tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of BKM120 and olaparib, and the combination of BYL719 and olaparib in patients with recurrent TNBC and HGSC.

To determine the safety and observed toxicities of the combination of BKM120 and olaparib, and the combination of BYL719 and olaparib in this population

To measure the drug levels of both BKM120 and olaparib, and both BYL719 and olaparib at different time points after they are started to see if either drug affects the metabolism and levels of the other. PK samples will be drawn in duplicate (one set to be sent to Astrazeneca and the second set to Novartis). BKM120 (or BYL719) and olaparib levels will be performed at the following timepoints:
prior to taking both BKM120 (or BYL719) and olaparib cycle 1, day 1.
Cycle 1, day 8: prior to dosing, 1, 2, 4, and 8 hours post am dosing.
Cycle 1, day 15: prior to dosing, 1, 2, 4, and 8 hours post am dosing.

To determine a preliminary anti-cancer activities of these combinations at the MTD and RP2D dose. Anti-cancer activities of these combinations will be measured by response rate by RECIST 1.1 in patients who have measurable cancer

(A) To determine the downstream signaling effects of the PI3-kinase pathway whenboth PI3-kinase and PARP are inhibited.
(B) To determine BRCA1 immnostaining, BRCA1 promoter hypermethylation and somatic mutations in BRCA1 and BRCA2 in archived formalin fixed paraffin embedded (FFPE) tissue and any new available tissues (pre- or post-treatment biopsies and biopsies or other tumor colelction for clinical care at the time of or following tumor progression)

Ursula A. Matulonis, MD

Principal Investigator

Novartis

AstraZeneca

Doses of AUC 5-6 of carboplatin in combination with 75 mg/m2 of docetaxel are easily combined, being myelosuppression the most important toxicity. This combination has been studied in metastatic breast cancer as well as in the neoadjuvant setting. The combination of taxanes and platinum salts is increasingly used as neoadjuvant chemotherapy for TNBC. The docetaxel-carboplatin (TCb) regimen is an active and tolerable regimen in metastatic and locally advanced breast cancer, and the efficacy and toxicity characterization in the clinical setting are regaining interest in the era where the role of anthracyclines is controversial in the adjuvant setting. The avoidance of potentially serious long-term toxicities in specific breast cancer subtypes is a real challenge in an attempt to individualize therapies.

Breast Cancer Stage II-III

Docetaxel 75mg/m2 day 1 and Carboplatin(AUC6)day 1, each 21 days for 6 cycles.

Docetaxel- Carboplatin

Hospital Universitario Gregorio Marañon

Predictors of Response to Neoadjuvant Docetaxel-Carboplatin Chemotherapy for Patients With Stage II and III Triple Negative Breast Cancer

The primary objective of the study is to identify predictors of response to docetaxel-carboplatin in patients with triple negative primary tumors. Response is defined as lack of invasive tumor in breast plus axilla after neoadjuvant chemotherapy (PCR, pathological complete response).

To identify predictors of good pathological response according to Symmans criteria (i.e. Symmans class 0+1)
To identify predictors of chemoresistance (class III od Symmans)
To assess the clinical response rate by standard methods (MRI, clinical examination, mammogram) in patients treated with this regimen.
To evaluate breast conserving surgery rate in patients treated with this regimen.
To evaluate the pCR rate in patients with known BRCA mutations.

triple negative breast neoplasms/vòmit

Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent Triple Negative Breast Cancer or High Grade Serous Ovarian Cancer

Predictors of Response to Neoadjuvant Docetaxel-Carboplatin Chemotherapy for Patients With Stage II and III Triple Negative Breast Cancer

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