Alisertib (MLN8237) in Participants With Ovarian, Fallopian Tube or Peritoneal Cancer Preceded by Phase 1 Study of MLN8237 Plus Paclitaxel Treatment of Ovary or Breast Cancer
Condition: Ovarian Carcinoma; Fallopian Tube Cancer; Peritoneal Cancer; Breast Carcinoma
MeSH terms: Carcinoma; Breast Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms
Intervention: Alisertib; Paclitaxel
Intervention description: Alisertib tablets; Paclitaxel intravenous infusion
Intervention MeSH terms: Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 191.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: RECIST: Response Evaluation Criteria in Solid Tumors; OC: Ovarian Cancer; GCIG: Gynecologic Cancer Intergroup; Breast carcinoma (Phase 1); Drug therapy

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).
    

Eligibility criteria:

        Inclusion Criteria:

        Each participant must meet all of the following inclusion criteria to be enrolled in the
        study:

          -  Female participants 18 years or older

          -  Previously treated, metastatic or locally recurrent malignancy with 1 of the following
             diagnoses, which has been confirmed histologically or cytologically: adenocarcinoma of
             the breast (Phase 1 only), recurrent epithelial ovarian, fallopian tube, or primary
             peritoneal carcinoma (Phase 1 and 2)

          -  In the Phase 1 portion of the study, participants with breast cancer must have
             received treatment with at least 1 but no more than 4 prior chemotherapy regimens not
             including regimens received in the neoadjuvant and/or adjuvant setting

          -  Participants with breast cancer must have measurable disease per Response Evaluation
             Criteria in Solid Tumors (RECIST) 1.1

          -  No antineoplastic therapy or radiotherapy within 3 weeks before enrollment (2 weeks
             for regimens with recovery expected within 7 to 14 days) and recovered from toxicities
             of prior therapy (except alopecia); the participant must have recovered from all
             treatment-related toxicities and must have evidence of progressive disease (PD) or
             persistent disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Adequate bone marrow, liver and renal function

          -  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

          -  Willing to comply with scheduled visits, treatment plan, laboratory tests and other
             trial procedures

          -  Suitable venous access

        Specific Inclusion Criteria for participants with Recurrent Ovarian, Fallopian Tube or
        Peritoneal Cancer:

          -  Prior treatments must have included a platinum and a taxane; the most recent treatment
             need not be a platinum-containing or taxane-containing regimen

          -  Disease must have recurred ≤ 12 months after discontinuation of platinum therapy

          -  Participants who previously received weekly taxane are potentially eligible, provided
             that they did not progress during therapy or within 3 months of completing therapy

          -  Participants with platinum-refractory disease, as defined by progression during
             primary or subsequent platinum-based therapy or persistent radiographic disease after
             primary or subsequent platinum-based therapy, will be included

          -  Participants must have measurable disease in target lesions or assessable disease
             (defined by cancer antigen-125 - CA-125 per protocol), and disease progression per
             Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or modified
             Gynecologic Cancer Intergroup (GCIG) CA-125 criteria

        Exclusion Criteria:

        Participants meeting any of the following exclusion criteria are not to be enrolled in the
        study:

          -  Prior treatment with an Aurora A-targeted agent (including MLN8237)

          -  Treatment with clinically significant enzyme inducers within 14 days prior to the
             first dose of MLN8237 and during the study

          -  Treatment with more than 4 cytotoxic chemotherapy regimens in the metastatic setting;
             prior therapy cannot include more than 2 prior taxane-containing regimen. Current use
             of tamoxifen, thalidomide, or any agent used as maintenance or consolidation therapy
             for OC.

          -  Known hypersensitivity to Cremophor® EL, paclitaxel or its components

          -  Prior history of ≥ Grade 2 neurotoxicity or any toxicity requiring discontinuation
             from taxane chemotherapy that is not resolved to ≤ Grade 1

          -  Comorbid or unresolved toxicity that would preclude administration of weekly
             paclitaxel

          -  Primary central nervous system malignancy or carcinomatous meningitis

          -  Symptomatic brain metastasis

          -  Inability to swallow oral medications or maintain a fast

          -  History of hemorrhagic or thrombotic cerebrovascular event in past 12 months

          -  Surgery within 3 weeks before study enrollment and not fully recovered

          -  Diagnosis or treatment of another malignancy within 2 years preceding first dose of
             MLN8237 and have any evidence of residual disease except nonmelanoma skin cancer or in
             situ malignancy completely resected

          -  Pregnant or lactating

          -  Serious illness that could interfere with protocol completion

          -  Investigational treatment 21 days prior to first dose of MLN8237

          -  Prior allogeneic bone marrow or organ transplantation

          -  Infection requiring systemic antibiotic therapy within 14 days prior to first dose of
             MLN8237

          -  Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or
             hepatitis C

          -  Radiotherapy to > 25% bone marrow or whole pelvic radiotherapy

          -  Requirement for constant administration of proton pump inhibitor, H2 antagonist, or
             pancreatic enzymes. Intermittent uses of antacids of H2 antagonists are allowed