A study of MLN8237 in patients with Ovarian or Breast Cancer to find the highest safe dose of MLN8237 given in combination with Paclitaxel,followed by further investigation of that dose in cancers of the ovary,fallopian tube or peritoneum to assess the efficacy of MLN8237 pluspaclitaxel compared to paclitaxel alone.
- Conditions
- Adenocarcinoma of the breast (Phase 1 only).Ovarian Cancer, defined to include recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (Phases 1 and 2).MedDRA version: 14.1Level: LLTClassification code 10058448Term: Peritoneal adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: LLTClassification code 10006173Term: Breast adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10061328Term: Ovarian epithelial cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10016180Term: Fallopian tube cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2009-011428-79-PL
- Lead Sponsor
- Millennium Pharmaceuticals, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 191
1. Female patients 18 years or older.
2. Previously treated, metastatic or locally recurrent malignancy with 1 of the 2 following diagnoses, which has been confirmed histologically or cytologically: a) adenocarcinoma of the breast (phase 1 only); or b) OC, defined to include recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (phases 1 and 2).
3. Patients with breast cancer must have received prior treatment with at least 1 but no more than 4 prior chemotherapy regimens for locally recurrent or metastatic disease, not including regimens received in the neoadjuvant and/or adjuvant setting.
4. In the phase 1 portion of the study, patients with breast cancer must have measurable disease (per RECIST, version 1.1; see Section 15.3 of the protocol).
5. No antineoplastic therapy or radiotherapy within the 3 weeks before enrollment (2 weeks for regimens with recovery expected within 7 to 14 days). The patient must have recovered (ie, = Grade 1 toxicity or patient’s baseline status, except alopecia) from all treatment related toxicities and must have evidence of PD or persistent disease. The patient must have experienced no more than Grade 2 non-hematologic toxicity attributed to a prior taxane therapy. No hormonal therapy except hormone replacement therapy or birth control medications.
6. ECOG performance status (PS) of 0 or 1 (refer to Section 15.1 of the protocol).
7. Adequate bone marrow function as defined by:
• Absolute neutrophil count (ANC) = 1,500 cells/mm3 (without need for growth factor support)
• Platelet count = 100,000 cells/mm3 (without need for transfusion or growth factor support)
• Hemoglobin level = 9 g/dL
8. Adequate liver function as defined by:
• Bilirubin < 1.5 times the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN (= 5 x ULN if due to liver metastases)
• serum albumin greater than the lower limit of normal (LLN)
9. Adequate renal function as defined by:
• Creatinine clearance = 30 mL/minute (can be calculated using serum creatinine value; see Section 15.2 of the protocol)
10. 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 contraception, at the same time, from the time of signing the ICF through 30 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
11. 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.
12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
13. Suitable venous access for the study-required blood sampling.
Specific Inclusion Criteria for Patients with Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer:
14. Prior treatments must have included a platinum and a taxane. The most recent treatment regimen (administered prior to enrollment) need not be a platinum containing or a taxane containing regimen.
• Recurrent disease must be documented within 12 months after discontinuation of platinum therapy, based on RECIST or GCIG CA-125 crit
Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
1. Prior treatment with an Aurora A targeted agent (including alisertib).
2. Treatment with clinically significant enzyme inducers within 14 days prior to the first dose of alisertib and during the study. Major prohibited enzyme inducers include the following:
•phenytoin
•carbamazepine
•phenobarbital
•rifampin
•rifabutin
•rifapentine
•St. John's wort
3. Treatment with more than 4 cytotoxic chemotherapy treatment regimens in the metastatic setting. A cytotoxic agent is defined as any agent that targets the genetic, mitotic, and/or metabolic pathways of dividing cells, resulting in toxicity to the bone marrow and/or gastrointestinal mucosa. A chemotherapy regimen is defined as 1 or more agents used continuously or discontinuously (ie, allowing a break or chemotherapy holiday) without the addition of a new agent. A regimen administered pre-operatively and continued after surgery is considered a single regimen. Hormonal therapy is not considered to be a chemotherapy regimen.
• The most recent treatment regimen need not be a platinum-containing or a taxane containing regimen.
• Prior therapy cannot include more than 2 prior taxane-containing regimens.
4. Current use of tamoxifen, thalidomide, or any agent used as maintenance or consolidation therapy for OC.
5. Known hypersensitivity to Cremophor® EL, paclitaxel, or its components.
6. Prior history of = Grade 2 neurotoxicity or any toxicity requiring discontinuation from taxane chemotherapy that is not resolved to = Grade 1.
7. Any comorbid condition or unresolved toxicity that would preclude administration of weekly paclitaxel.
8. Diagnosis of primary CNS malignancy or carcinomatous meningitis.
9. Patient has symptomatic brain metastasis. Patients with brain metastases must:
• Have stable neurologic status following local therapy (surgery or radiation) for at least 2 weeks after completion of the definitive therapy; and
• Be without neurologic dysfunction that would confound the evaluation of neurologic and other AEs.
10. Inability to swallow PO administered medications or to maintain a fast as required before and after alisertib administration.
11. History of hemorrhagic or thrombotic cerebrovascular event in the past 12 months.
12. Surgery within 3 weeks before study enrollment and not fully recovered to baseline or to a stable clinical status.
13. Diagnosis of or treated for another malignancy within 2 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type, including patients with Stage IA or IB endometrioid carcinomas, are not excluded if they have undergone complete resection.
14. Patients who are lactating or have a positive serum pregnancy test during the screening period.
15. Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method