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

• Conditions: Platinum-refractory and platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma; MedDRA version: 11.1Level: LLTClassification code 10033131Term: <Manually entered code. Term in E.1.1>; MedDRA version: 11.1Level: LLTClassification code 10016180Term: <Manually entered code. Term in E.1.1>; MedDRA version: 11.1Level: LLTClassification code 10052171Term: <Manually entered code. Term in E.1.1>

• Registration Number: EUCTR2008-006979-72-PL
• Lead Sponsor: Millennium Pharmaceuticals, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-06-23
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 56

Inclusion Criteria

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

1. Female patients 18 years or older

2. Patients must have a diagnosis of histologically or cytologically confirmed epithelial
ovarian, fallopian tube, or primary peritoneal carcinoma.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

4. Patients who:

• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 2 effective methods of nonhormonal contraception, at the same time, from the time of signing the informed consent form (ICF) through 30 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.

5. The patient or the patient’s legal representative is able to provide written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

6. Clinical laboratory values as specified below within 7 days before study entry:

• Absolute neutrophil count (ANC) = 1,500/µL
• Platelet count =100,000/ µL
• Total bilirubin must be less than 1.5 times the upper limit of the normal range
(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 their elevation can be reasonably ascribed to the presence of metastatic disease in liver.
• Creatinine clearance as calculated by the method of Cockroft and Gault = 30 mL/minute.

7. Platinum-refractory malignant disease or platinum-resistant malignant disease:

• Platinum-refractory malignant disease, characterized by a lack of response, progression, or recurrence of malignant disease during treatment with a platinum-based treatment regimen; OR
• Platinum-resistant malignant disease, characterized by progression or recurrence
of malignant disease within 6 months after the last dose of platinum on a platinum-based treatment regimen

8. Measurable neoplastic disease according to the RECIST criteria, ie, 1 or more
lesions that can be accurately measured in at least 1 dimension (longest dimension to be recorded) and at least 2 cm by conventional techniques or at least 1 cm by spiral CT scan and at least 1 target lesion to assess response. Tumors within a previously irradiated field are considered nontarget lesions unless progression is documented or a biopsy is obtained to confirm persistence of malignancy 90 days or more following completion of radiotherapy.

OR

A CA 125 level of > 40 units/mL AND clinical evidence of neoplastic disease
(eg, ascites, pleural effusion, peritoneal implantation, etc). Patients who simply have
an elevated CA 125 level without clinical evidence of neoplastic disease are NOT eligible for the study.

9. Recovered (ie, = Grade 1 toxicity or patient’s baseline status) from the reversible
effects of prior antineoplastic therapy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

1. Pregnant or lactating

2. Any serious medical or psychiatric illness that could, in the investigator’s opinion,
potentially interfere with the completion of treatment according to this protocol

3. Treatment with any investigational products within 28 days before the first dose of
study drug

4. Receipt of more than 4 regimens of prior systemic therapy, 2 of which may be platinum-based cytotoxic chemotherapy, 1 of which may be a nonplatinum cytotoxic
regimen, and 1 biological therapy NOT part of a cytotoxic regimen

5. Known CNS metastases

6. Prior allogeneic bone marrow or organ transplantation

7. Radiotherapy within 21 days preceding the first dose of study drug

8. Radiotherapy to more than 25% of the hematopoietically active bone marrow

9. Major surgery within 14 days preceding the first dose of study drug

10. Infection requiring systemic antibiotic therapy within 14 days preceding the first
dose of study drug, or other severe infection

11. Inability to swallow orally administered medication

12. Diagnosis or treatment of another malignancy within 2 years preceding the first dose of study drug except for nonmelanoma skin cancer that has been completely
resected, or any in situ malignancy that has been completely resected

13. Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or
hepatitis C. Testing is not required in the absence of clinical findings or suspicion.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To estimate the objective antitumor response rate of MLN8237 using the Response Evaluation Criteria in Solid tumors (RECIST criteria) or CA 125 criteria in patients with platinum-refractory or platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.;Secondary Objective: To estimate the progression-free survival (PFS), duration of response (DOR), time to disease progression (TTP), and the clinical benefit (response and stable disease [SD]) associated with MLN8237.<br><br>To further characterize the adverse event (AE) profile associated with MLN8237.;Primary end point(s): Combined objective response rate, defined as CR+PR by RECIST criteria or<br>response by CA 125 criteria.