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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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Female
Ovarian Carcinoma, Fallopian Tube Cancer, Peritoneal Cancer, Breast Carcinoma

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Trial Information

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


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To assess safety and tolerability of MLN8237 plus weekly paclitaxel by determining the maximum tolerated dose of MLN8237

Outcome Time Frame:

24 months

Safety Issue:

Yes

Principal Investigator

Medical Monitor

Investigator Role:

Study Director

Investigator Affiliation:

Millennium Pharmaceuticals, Inc.

Authority:

United States: Food and Drug Administration

Study ID:

C14008

NCT ID:

NCT01091428

Start Date:

May 2010

Completion Date:

September 2014

Related Keywords:

  • Ovarian Carcinoma
  • Fallopian Tube Cancer
  • Peritoneal Cancer
  • Breast Carcinoma
  • RECIST: Response Evaluation Criteria in Solid Tumors
  • OC: Ovarian Cancer
  • GCIG: Gynecologic Cancer Intergroup
  • Breast carcinoma (Phase 1)
  • Breast Neoplasms
  • Carcinoma
  • Ovarian Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms

Name

Location

Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
The University of Texas MD Anderson Cancer CenterHouston, Texas  77030-4009