Alisertib in Treating Patients With Advanced or Metastatic Sarcoma

This study has suspended participant recruitment.
(Temporarily stopped for assessment)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01653028
First received: July 26, 2012
Last updated: August 13, 2014
Last verified: March 2014
  Purpose

This phase II trial studies how well alisertib works in treating patients with advanced or metastatic sarcoma. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Adult Alveolar Soft-part Sarcoma
Adult Angiosarcoma
Adult Epithelioid Sarcoma
Adult Extraskeletal Chondrosarcoma
Adult Fibrosarcoma
Adult Leiomyosarcoma
Adult Liposarcoma
Adult Neurofibrosarcoma
Chondrosarcoma
Endometrial Stromal Sarcoma
Mast Cell Sarcoma
Metastatic Adult Malignant Fibrous Histiocytoma of Bone
Ovarian Carcinosarcoma
Ovarian Sarcoma
Recurrent Adult Malignant Fibrous Histiocytoma of Bone
Recurrent Adult Soft Tissue Sarcoma
Small Intestine Leiomyosarcoma
Stage III Adult Soft Tissue Sarcoma
Stage IV Adult Soft Tissue Sarcoma
Drug: alisertib
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of MLN8237 in Advanced / Metastatic Sarcoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • The confirmed response rate (CR/PR) [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
    The overall response rate (CR + PR) will be estimated and a 90% confidence interval provided.


Secondary Outcome Measures:
  • PFS [ Time Frame: The time between registration to disease progression or death, assessed up to 18 months ] [ Designated as safety issue: No ]
    The distribution will be estimated by the methods of Kaplan and Meier. The estimates of PFS at specific time points will be calculated (eg, median, 1 year PFS).

  • OS [ Time Frame: The time between registration and death, assessed up to 18 months ] [ Designated as safety issue: No ]
    The distribution will be estimated by the methods of Kaplan and Meier. The estimates of survival at specific time points will be calculated (eg, median, 6 month survival).

  • Incidence of adverse events, assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]
    Adverse events will be summarized using summary statistics and frequency tables for each separate cohort. Analyses will be descriptive in nature.


Other Outcome Measures:
  • Biopsy protein levels [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    For tumor biopsies, pre- and post-treatment protein levels will be compared by Wilcoxon signed-rank test (for paired samples). The association of response or clinical benefit with the presence or absence of markers of pathway inhibition in patient tumors will be tested using Fisher's exact test.

  • Biopsy protein levels [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
    For tumor biopsies, pre- and post-treatment protein levels will be compared by Wilcoxon signed-rank test (for paired samples). The association of response or clinical benefit with the presence or absence of markers of pathway inhibition in patient tumors will be tested using Fisher's exact test.

  • Changes in FLT-PET uptake [ Time Frame: Baseline to 1 week ] [ Designated as safety issue: No ]
    Changes in FLT-PET uptake at baseline versus after one week of treatment will be compared by Wilcoxon Rank Sum test between responders and non-responders defined by RECIST criteria. Fisher's exact test will be used to assess the association between dichotomous change in FLT-PET uptake change and RECIST response status.


Estimated Enrollment: 135
Study Start Date: August 2012
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (alisertib)
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
Given PO
Other Names:
  • Aurora A kinase inhibitor MLN8237
  • MLN8237
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the response rate (complete response [CR] + partial response [PR]) assessed for patients within each cohort: liposarcoma (cohort 1); leiomyosarcoma (non-uterine) (cohort 2); undifferentiated sarcoma (including pleomorphic undifferentiated sarcoma, formerly known as malignant fibrous histiocytoma, and myxofibrosarcoma) (cohort 3); malignant peripheral nerve sheath tumor (cohort 4); and other sarcomas (cohort 5).

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival (PFS) and overall survival (OS) for patients treated with alisertib (MLN8237) in each cohort.

II. To assess the adverse events associated with patients treated with MLN8237 in each cohort.

TERTIARY OBJECTIVES:

I. To correlate potential clinical benefit with markers of aurora kinase inhibition in pre- and post-treatment tumor biopsies.

II. To correlate clinical outcome with change in fluorine F 18 fluorothymidine (FLT)-positron emission tomography (PET) uptake at baseline versus after one week of treatment (i.e., week 2 of cycle 1).

OUTLINE:

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

After completion of study treatment, patients are followed up every 6 months for 18 months.

  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed sarcoma that is metastatic and/or locally advanced or locally recurrent and unresectable; confirmation of pathologic diagnosis will be performed at the registering site; patients will been rolled on one of five cohorts of the study:

    • Cohort 1: liposarcoma
    • Cohort 2: leiomyosarcoma (non-uterine)
    • Cohort 3: undifferentiated sarcoma (including malignant fibrous histiocytoma and myxofibrosarcoma)
    • Cohort 4: malignant peripheral nerve sheath tumor
    • Cohort 5: other sarcomas
  • Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors(RECIST) 1.1; note: defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Any number of prior therapies is permitted; note: the last dose of systemic therapy (including tyrosine kinase inhibitors) must have been given >= 4 weeks prior to initiation of study therapy; patients receiving BCNU or mitomycin C must have received their last dose of such therapy at least 6 weeks prior to initiation of therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelet count >= 100,000/mcL
  • Total bilirubin =< 1.5 times institutional upper limit of normal (ULN)
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (alanine aminotransferase [AST]) < 3 times ULN if no liver metastases or < 5 times ULN if liver metastases present
  • Creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min/1.73m^2 for patients with creatinine levels above institutional normal
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MLN8237 administration
  • Ability to understand and the willingness to sign a written informed consent document
  • According to current guidelines, patients must be able to take oral medication and to maintain a fast as required for approximately one hour before and two hours after MLN8237 administration

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients who have had radiation therapy to more than 25% of the bone marrow; whole pelvic radiation is considered to be over 25%
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases
  • 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
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, New York Heart Association (NYHA) class II-IV heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women; women of child-bearing potential must have a negative serum or urine pregnancy test within 7 days prior to registration; breastfeeding should be discontinued if the mother is treated with MLN8237
  • Leiomyosarcoma of the uterus
  • Patients known to be human immunodeficiency virus (HIV)-positive on antiretroviral therapy
  • Prior allogeneic bone marrow or organ transplantation
  • 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
  • Requirement for constant administration of proton pump inhibitor, histamine-2 (H2) antagonist, or pancreatic enzymes; note: intermittent uses of antacids or H2 antagonists are allowed
  • Inability to swallow oral medication or to maintain a required fast for approximately one hour before and two hours after MLN8237 administration or any condition that would modify small bowel absorption of oral medications, including malabsorption or resection of pancreas or upper bowel
  • 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
  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: NCT01653028

  Show 241 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Mark Dickson Alliance for Clinical Trials in Oncology
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01653028     History of Changes
Other Study ID Numbers: NCI-2012-01991, NCI-2012-01991, CDR0000737403, CALGB-A091102, A091102, A091102, U10CA031946, U10CA180821
Study First Received: July 26, 2012
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sarcoma
Leiomyosarcoma
Liposarcoma
Chondrosarcoma
Hemangiosarcoma
Carcinosarcoma
Mixed Tumor, Mullerian
Histiocytoma
Histiocytoma, Benign Fibrous
Fibrosarcoma
Histiocytoma, Malignant Fibrous
Sarcoma, Alveolar Soft Part
Neurofibrosarcoma
Sarcoma, Endometrial Stromal
Ovarian Neoplasms
Mast-Cell Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Muscle Tissue
Neoplasms, Adipose Tissue
Neoplasms, Connective Tissue
Neoplasms, Vascular Tissue
Neoplasms, Complex and Mixed
Neoplasms, Fibrous Tissue
Neurofibroma
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Peripheral Nervous System Neoplasms
Nervous System Neoplasms

ClinicalTrials.gov processed this record on September 16, 2014