Clinical trial NCT00853307: MLN8237 for Treatment of Participants With Ovarian, Fallopian Tube, or Peritoneal Carcinoma
Official title: A Phase 2 Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in the Treatment of Patients With Platinum-Refractory or Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Carcinoma
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2009-03-02
Enrollment: 31
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Female participants 18 years or older.
2. Histologically or cytologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
4. 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.
5. Able to provide written informed consent.
6. 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
7. Platinum-refractory or -resistant disease.
8. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) OR Cancer antigen (CA) 125 level of \> 40 units/mL AND clinical evidence disease.
9. Recovered from effects of prior therapy.

Exclusion Criteria:

1. Pregnant or lactating.
2. Serious illness that could interfere with protocol completion.
3. Investigational treatment 28 days prior to first dose.
4. Maximum 4 prior systemic therapies: 2 platinum-based, 1 nonplatinum cytotoxic, 1 biological.
5. Known Central Nervous System metastases.
6. Prior allogeneic bone marrow or organ transplantation.
7. Radiotherapy within 21 days prior to first dose.
8. Radiotherapy to \> 25% bone marrow.
9. Major surgery or infection requiring systemic antibiotic therapy within 14 days prior to first dose.
10. Inability to swallow orally administered medication.
11. 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.
12. Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C.

Primary outcomes:
measure: Combined Best Overall Response Rate Based on Investigator Assessment
timeFrame: 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)
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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)
measure: Duration Of Response (DOR)
timeFrame: 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)
measure: Time To Progression (TTP)
timeFrame: 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)
measure: Clinical Benefit Rate
timeFrame: 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)
measure: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events
timeFrame: First dose to 30 days past last dose (Up to 18.9 Months)
measure: Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events
timeFrame: 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)
measure: Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events
timeFrame: Baseline, Cycle 1 Days 8 and 15, then Every cycle Days 1, 8 and 15 to End of Treatment Up to 18.0 Months
Other outcomes:
Locations:
city: Berkeley Heights
country: United States
facility: Summit Medical Group
state: New Jersey
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: