Trial record 1 of 1 for:    C14008
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MLN8237 in Patients With Ovarian, Fallopian Tube or Peritoneal Cancer Preceded by Phase 1 Study of MLN8237 Plus Paclitaxel Treatment of Ovary or Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01091428
First received: March 17, 2010
Last updated: August 14, 2013
Last verified: August 2013
  Purpose

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 patients with advanced breast cancer (Phase 1 portion only) and recurrent ovarian cancer (both Phase 1 and Phase 2 portions).


Condition Intervention Phase
Ovarian Carcinoma
Fallopian Tube Cancer
Peritoneal Cancer
Breast Carcinoma
Drug: MLN8237 + Paclitaxel
Drug: MLN8237+Paclitaxel vs. Paclitaxel alone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase 2 Study of MLN8237, an Aurora A Kinase Inhibitor, Plus Weekly Paclitaxel or Weekly Paclitaxel Alone in Patients With Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer, Preceded by a Phase 1 Portion in Patients With Ovarian or Breast Cancer

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • To assess safety and tolerability of MLN8237 plus weekly paclitaxel by determining the maximum tolerated dose of MLN8237 [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • In Phase 1 study, to determine the recommended dose and schedule of MLN8237 and dose of paclitaxel for Phase 2 combination treatment arm [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • In Phase 2 study, to assess progression-free survival (PFS) [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • In Phase 1 study, to characterize effect of concomitant administration of MLN8237 on the pharmacokinetics (PK) of paclitaxel [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • In Phase 1 study, to characterize the pharmacokinetics (PK) of MLN8237 administered concomitantly with paclitaxel [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • In Phase 1 study, to assess best overall combined response rate in patients with recurrent ovarian cancer or breast cancer [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • In Phase 2 study, to estimate overall response rate (ORR), duration of response (DOR), time to disease progression (TTP) & overall survival (OS) associated w/ MLN8237 + weekly paclitaxel & weekly paclitaxel alone in patients w/ recurrent ovarian cancer [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • To assess the banked tumor specimens for candidate markers of response to MLN8237 and taxanes [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • In Phase 2 study, to assess adverse events, serious adverse events, clinical laboratory values and vital sign measurements [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 172
Study Start Date: May 2010
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 (MLN8237 + Paclitaxel) Drug: MLN8237 + Paclitaxel

Phase 1:

MLN8237 administered orally twice daily on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel (Days 1, 8, 15) as an intravenous infusion repeated in 28-day cycles

Drug: MLN8237+Paclitaxel vs. Paclitaxel alone

Phase 2:

Arm 1:

MLN8237 administered orally twice daily on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel (Days 1, 8, 15) as an intravenous infusion repeated in 28-day cycles

Arm 2:

Paclitaxel will be administered as an intravenous infusion on Days 1, 8 and 15 of each 28-day cycle

Active Comparator: Arm 2 (Paclitaxel) Drug: MLN8237+Paclitaxel vs. Paclitaxel alone

Phase 2:

Arm 1:

MLN8237 administered orally twice daily on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel (Days 1, 8, 15) as an intravenous infusion repeated in 28-day cycles

Arm 2:

Paclitaxel will be administered as an intravenous infusion on Days 1, 8 and 15 of each 28-day cycle


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

  • Female patients 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, patients 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
  • Patients 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 patient must have recovered from all treatment-related toxicities and must have evidence of 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 Patients 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
  • Patients who previously received weekly taxane are potentially eligible, provided that they did not progress during therapy or within 3 months of completing therapy
  • Patients 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
  • Patients must have measurable disease in target lesions or assessable disease (defined by 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:

Patients 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 regimens
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01091428

Locations
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01091428     History of Changes
Other Study ID Numbers: C14008
Study First Received: March 17, 2010
Last Updated: August 14, 2013
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Poland: Ministry of Health

Keywords provided by Millennium Pharmaceuticals, Inc.:
RECIST: Response Evaluation Criteria in Solid Tumors
OC: Ovarian Cancer
GCIG: Gynecologic Cancer Intergroup
Breast carcinoma (Phase 1)

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators

ClinicalTrials.gov processed this record on August 18, 2014