Alisertib in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus

NCT01637961 | Completed Phase 2 Results DMC

• 5 other identifiers: NCI-2012-01982GOG-0231DCDR0000736350U10CA180868U10CA027469
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 50

Brief Summary

This phase II trial studies how well alisertib works in treating patients with leiomyosarcoma of the uterus that has come back or persistent. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Recurrent Uterine Corpus Sarcoma; Uterine Corpus Leiomyosarcoma

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) > 6 Months

  Whether or not the patient survived progression-free for at least 6 months. 90% confidence interval (Bonferroni Corrected). Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Progression includes the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

  Assessed every other cycle for the first 6 months; then every 3 months from the date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.

• Tumor Response

  Complete and Partial Tumor Response by RECIST 1.1. Patient response uses best overall response while on therapy. Complete response is defined as the disappearance of all target lesions and non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in the short axis to \<10 mm. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete or partial response requires confirmation at greater than or equal to 4 weeks from initial documentation.

  Every other cycle for the first 6 months; then every 3 months thereafter until withdrawal from study treatment or disease progression is confirmed.

Secondary Outcomes (3)

• Overall Survival

  From study entry to death or last contact, up to 5 years.

• Number of Participants With Adverse Events as Assessed by NCI CTCAE Version 4.0

  Every cycle during treatment and 30 days after the last treatment, up to 5 years.

• Progression Free Survival

  every other cycle for the first 6 months; then every 3 months thereafter until disease progression is confirmed; up to 5 years

Other Outcomes (1)

• Aurora A Kinase Expression

  Up to 5 years

Study Arms (1)

Treatment (alisertib)

EXPERIMENTAL

Patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Alisertib; Other: Laboratory Biomarker Analysis

Interventions

Alisertib DRUG

Given PO

Also known as: Aurora A Kinase Inhibitor MLN8237, MLN-8237, MLN8237

Treatment (alisertib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (alisertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have incurable recurrent or persistent uterine leiomyosarcoma; histologic confirmation of the original primary tumor is required
• Patients must have measurable disease; measurable disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1); measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be \>= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI), or caliper measurement by clinical exam; or \>= 20 mm when measured by chest x-ray; lymph nodes must be \>= 15 mm in short axis when measured by CT or MRI
• Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST version 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
• Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG phase III protocol for the same patient population (12/10/2012)
• Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2; patients who have received two prior regimens must have a GOG performance status of 0 or 1
• Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection \[UTI\])
• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
• Any other prior therapy directed at the malignant tumor, including chemotherapy and immunologic agents, must be discontinued at least three weeks prior to registration (12/10/2012)
• Any prior radiation therapy must be discontinued at least four weeks prior to registration (12/10/2012)
• Patients must have had at least one prior chemotherapeutic regimen for management of leiomyosarcoma
• Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease (12/10/2012)
• Patients must NOT have received any prior therapy directed at Aurora kinase for management of recurrent or persistent disease; patients who were treated on GOG-0250 (gemcitabine + docetaxel plus bevacizumab vs placebo) are eligible; treatment on GOG-0250 would count as ONE prior regimen
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL

You may not qualify if:

• Patients who have had prior therapy with MLN8237 or taken part in a study of an investigational compound or device within 4 weeks of entering this study
• Patients who have had surgery (excluding biopsy), radiotherapy, or chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the planned start of protocol treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients who have had hormonal agents within 1 week of the planned start of protocol treatment
• Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, carcinoma in situ of the cervix, or ductal carcinoma in situ of the breast, are excluded if there is any evidence of other malignancy being present within the last three years
• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of uterine leiomyosarcoma within the last three years are excluded; thus, patients with a history of prior pelvic radiation for uterine leiomyosarcoma are eligible; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
• Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of uterine leiomyosarcoma within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
• Patients who are nursing because there is an unknown but potential risk for adverse events in nursing infants from MLN8237
• Patients with a history of central nervous system metastases and/or carcinomatous meningitis
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN8237, including but not limited to established allergic reaction to benzodiazepines
• Patients who are known to be human immunodeficiency virus (HIV) positive
• Patients who have had prior allogeneic bone marrow or organ transplantation
• Patients with a known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen; or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237
• Patients who require constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed
• Patients who are unable to swallow oral medication or to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration or any condition that would modify small bowel absorption of oral medications, including malabsorption, or resection of pancreas or upper bowel
• Patients who have had treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine, oxcarbazepine, primidone or phenobarbital, or rifampin, rifabutin, rifapentine, or St. John's wort within 14 days prior to the first dose of MLN8237 and during the study
• Patients who have had a myocardial infarction within 6 months prior to enrollment or have New York Heart Association (NYHA) class III (marked limitation of physical activity, comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea) or IV (unable to carry out any physical activity without discomfort, symptoms of cardiac insufficiency at rest, if any physical activity is undertaken, discomfort is increased) heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• NRG Oncology: collaborator

Study Sites (50)

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105, United States

Location

The Hospital of Central Connecticut

New Britain, Connecticut, 06050, United States

Location

Florida Hospital Orlando

Orlando, Florida, 32803, United States

Location

University of Hawaii Cancer Center

Honolulu, Hawaii, 96813, United States

Location

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, 83706, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Sudarshan K Sharma MD Limted-Gynecologic Oncology

Hinsdale, Illinois, 60521, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, 46260, United States

Location

McFarland Clinic PC-William R Bliss Cancer Center

Ames, Iowa, 50010, United States

Location

Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

Iowa-Wide Oncology Research Coalition NCORP

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates-Des Moines

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates-Laurel

Des Moines, Iowa, 50314, United States

Location

Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314, United States

Location

Iowa Lutheran Hospital

Des Moines, Iowa, 50316, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, 48106-0995, United States

Location

Michigan Cancer Research Consortium NCORP

Ann Arbor, Michigan, 48106, United States

Location

Beaumont Hospital-Dearborn

Dearborn, Michigan, 48124, United States

Location

Saint John Hospital and Medical Center

Detroit, Michigan, 48236, United States

Location

Hurley Medical Center

Flint, Michigan, 48502, United States

Location

Genesys Regional Medical Center

Grand Blanc, Michigan, 48439, United States

Location

Allegiance Health

Jackson, Michigan, 49201, United States

Location

Sparrow Hospital

Lansing, Michigan, 48912, United States

Location

Saint Mary Mercy Hospital

Livonia, Michigan, 48154, United States

Location

Saint Joseph Mercy Oakland

Pontiac, Michigan, 48341, United States

Location

Lake Huron Medical Center

Port Huron, Michigan, 48060, United States

Location

Saint Mary's of Michigan

Saginaw, Michigan, 48601, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Cancer Research for the Ozarks NCORP

Springfield, Missouri, 65804, United States

Location

Mercy Hospital Springfield

Springfield, Missouri, 65804, United States

Location

CoxHealth South Hospital

Springfield, Missouri, 65807, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

Southeast Clinical Oncology Research (SCOR) Consortium NCORP

Winston-Salem, North Carolina, 27104, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

Location

Lake University Ireland Cancer Center

Mentor, Ohio, 44060, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma, 74146, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Women and Infants Hospital

Providence, Rhode Island, 02905, United States

Location

AnMed Health Cancer Center

Anderson, South Carolina, 29621, United States

Location

Memorial Hermann Texas Medical Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Interventions

MLN 8237

Results Point of Contact

• Title: Angela M. Kuras, Associate Director of Data Management
• Organization: NRG Oncology Statistics and Data Management Center - Buffalo

kurasa@nrgoncology.org

716-845-7733

Study Officials

• David Hyman

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2012
• First Posted: July 11, 2012
• Study Start: August 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: February 11, 2017
• Last Updated: July 23, 2019
• Results First Posted: July 17, 2015

Record last verified: 2019-07

Locations

US (50)