Clinical trial NCT01091428
Conditions: Ovarian Carcinoma Fallopian Tube Cancer Peritoneal Cancer Breast Carcinoma
Keywords: RECIST: Response Evaluation Criteria in Solid Tumors OC: Ovarian Cancer GCIG: Gynecologic Cancer Intergroup Breast carcinoma (Phase 1) Drug therapy
Sponsor: Millennium Pharmaceuticals, Inc.
Start date: 2010-04-16; Completion date: 2017-07-19
Enrollment: 191 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is an open-label, multicenter study with a nonrandomized Phase 1 portion and an open-label, randomized, Phase 2 portion evaluating MLN8237 in combination with weekly paclitaxel in adult female participants with advanced breast cancer (Phase 1 portion only) and recurrent ovarian cancer (both Phase 1 and Phase 2 portions).

Detailed description:
The drug tested in this study was called alisertib. Alisertib was tested to treat people who have ovarian and breast cancer. This study looked at safety, any anti-tumor effect, and it also determined a recommended dose of alisertib plus paclitaxel to take into further studies. Pharmacokinetic blood samples were studied to characterize any effects on the concentration of each of the drugs when administered together.

The study enrolled 191 patients. Participants with Breast Cancer and Ovarian Cancer received one of the following escalating doses of alisertib in combination with paclitaxel in the Phase 1 lead-in portion of the study:

* Alisertib 10 mg BID + Paclitaxel 80 mg/m\^2
* Alisertib 20 mg BID + Paclitaxel 80 mg/m\^2
* Alisertib 20 mg BID + Paclitaxel 60 mg/m\^2
* Alisertib 30 mg BID + Paclitaxel 60 mg/m\^2
* Alisertib 40 mg BID + Paclitaxel 60 mg/m\^2
* Alisertib 50 mg BID + Paclitaxel 60 mg/m\^2

Once the maximum tolerated dose (MTD)/ recommended phase 2 dose (RP2D) was determined, participants were randomized to receive the following treatments in the Phase 2 portion of the study:

* Alisertib 40 mg BID + Paclitaxel 60 mg/m\^2
* Paclitaxel 80 mg/m\^2

This multi-center trial was conducted in the United States, Poland and France. The overall time to participate in this study was approximately 5 years. Participants made multiple visits to the clinic, and who did not experience disease progression (PD) were followed off-treatment once every 8 weeks until the occurrence of 110 progression-free survival (PFS) events.

Arms: arm 1: Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m\^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). arm 2: Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m\^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). arm 3: Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m\^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). arm 4: Paclitaxel 80 mg/m\^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).
Interventions: intervention 1: Alisertib intervention 2: Paclitaxel
Intervention descriptions: intervention 1: Alisertib tablets intervention 2: Paclitaxel intravenous infusion

Protocol documents: