MLN8237 for Treatment of Participants With Ovarian, Fallopian Tube, or Peritoneal Carcinoma

Phase 2

Completed

Conditions: Ovarian Carcinoma

Interventions: Drug: Alisertib

Registration Number: NCT00853307

Lead Sponsor: Millennium Pharmaceuticals, Inc.

Brief Summary: The purpose of this study is to evaluate the anti-tumour activity of alisertib (MLN8237) in the treatment of participants with platinum-refractory or platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinomas.

Detailed Description: The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have platinum-refractory or platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. This study looked at the antitumor activity by response rate who would take alisertib.

The study enrolled 31 patients. Participants were categorized as per the disease state into 2 categories, refractory and resistant. Participants received:

• Alisertib 50 mg

All participants took alisertib 50 mg capsules every 12 hours each day for 7 days followed by a 14-day rest period in a 21-day cycle (up to 26 cycles).

This multi-center trial was conducted in France, Poland and the United States. The overall time to participate in this study was 12 months, unless it is determined that a participant would benefit from continued therapy beyond 12 months. Participants made multiple visits to the clinic, and were contacted up to a maximum of every 12 weeks up to 12 months after last dose of study drug for follow-up assessments.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 31

Inclusion Criteria

Female participants 18 years or older.
Histologically or cytologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Postmenopausal at least 1 year, OR
- Surgically sterile, OR
- If childbearing potential, agree to 2 effective methods of nonhormonal contraception, or agree to completely abstain from heterosexual intercourse.
Able to provide written informed consent.
Within 7 days before study:
- Absolute neutrophils (ANC) ≥ 1,500/μL
- Platelets ≥100,000/ μL
- Total bilirubin must be < 1.5 times upper limit of the normal (ULN)
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be ≤ 2.5 times the ULN. AST and ALT may be elevated up to 5 times the ULN if ascribed to metastatic liver disease.
- Creatinine clearance ≥ 30 mL/minute
Platinum-refractory or -resistant disease.
Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) OR Cancer antigen (CA) 125 level of > 40 units/mL AND clinical evidence disease.
Recovered from effects of prior therapy.

Exclusion Criteria

Pregnant or lactating.
Serious illness that could interfere with protocol completion.
Investigational treatment 28 days prior to first dose.
Maximum 4 prior systemic therapies: 2 platinum-based, 1 nonplatinum cytotoxic, 1 biological.
Known Central Nervous System metastases.
Prior allogeneic bone marrow or organ transplantation.
Radiotherapy within 21 days prior to first dose.
Radiotherapy to > 25% bone marrow.
Major surgery or infection requiring systemic antibiotic therapy within 14 days prior to first dose.
Inability to swallow orally administered medication.
Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected.
Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Alisertib 50 mg	Alisertib	Alisertib 50 mg, capsules, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 26 Cycles).

Primary Outcome Measures

Name	Time	Method
Combined Best Overall Response Rate Based on Investigator Assessment	Every 2 cycles up to 12 months until progressive disease (PD); Participants who discontinue study drug before PD: Follow-Up (FU)-every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)	Combined objective response rate is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 or response by Cancer antigen (CA) 125 criteria. According to RECIST: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions. CA 125 response criteria is defined as either: A 50% decrease from 2 initially elevated samples; the sample demonstrating the 50% decrease must have been confirmed by a fourth sample 28 days later (a total of 4 samples required) or A serial decrease of \> 75% over 3 samples; the third sample was to be obtained 28 days after the second (a total of 3 samples required).

Secondary Outcome Measures

Name	Time	Method
Time To Progression (TTP)	Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)	TTP is defined as the time in days from the date of first study drug administration to the date of first documentation of PD. PD is defined as 20% increase in the sum of the longest diameter of target lesions.
Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events	First dose to 30 days past last dose (Up to 18.9 Months)	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events	Baseline, Cycle 1 Days 8 and 15, then Day 1 of every cycle (21 days), End of Treatment, End of Study/FU every 12 weeks for up to 12 months (Up to 22 Months)	Vital signs included blood pressure, pulse rate, and oral temperature collected throughout the study. . A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug.
Progression Free Survival (PFS)	Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)	PFS is defined as the time in days from the date of first study drug administration to the date of first documented Progressive Disease (PD) or death. PD is defined as 20% increase in the sum of the longest diameter of target lesions. CA 125 progression for participants with normal CA 125 levels is defined as a CA 125 level \> 2 times the upper limit of normal and for participants with elevated values during the trial, is defined as a CA 125 level greater than 2 times the nadir value of CA 125. For a participant who has not progressed and has not died, PFS is censored at the last response assessment that is stable disease (SD) or better.
Clinical Benefit Rate	Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)	Clinical benefit rate is defined as the percentage of participants with response and stable disease (SD), where in order for SD to qualify as having clinical benefit, there must be no progression of neoplastic disease for at least 4 treatment cycles.
Duration Of Response (DOR)	Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)	DOR is defined as the time from the date of first documentation of a confirmed response to the date of first documented PD. PD is defined as 20% increase in the sum of the longest diameter of target lesions.
Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events	Baseline, Cycle 1 Days 8 and 15, then Every cycle Days 1, 8 and 15 to End of Treatment Up to 18.0 Months	Laboratory tests included Hematology and Chemistry. Abnormal laboratory value were assessed as an AE if the value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.