Aurora A Kinase Inhibitor MLN8237 in Treating Patients With Unresectable Stage III-IV Melanoma

NCT01316692 | Terminated Phase 2 Results DMC

• 3 other identifiers: VICC MEL 1036NCI-2010-02322R01FD003522
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Aurora A kinase inhibitor MLN8237 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well Aurora A kinase inhibitor MLN8237 works in treating patients with unresectable stage III-IV melanoma Funding Source - FDA OOPD

Conditions

Recurrent Melanoma; Stage IIIc Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  If 2 or more of 23 pts show CR/PR in stage 1, then an additional 33 pts will be enrolled in stage 2. If 6 or more of the total 56 pts show CR/PR at 18 weeks, then further clinical trials will be warranted. Per Response Evaluation Criteria in Solid Tumor (RECIST)1.1: Complete response (CR): disappearance of all target lesions. Partial response (PR): \>=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.

  At 18 weeks

Secondary Outcomes (3)

• Progression-free Survival

  On treatment date to last follow-up, disease progression or death for any reason, up to 5 years

• Overall Survival

  On treatment date to last follow-up or death for any reason, up to 5 years

• Number of Grade 3 and 4 Study-related Toxicities

  at 18 weeks

Other Outcomes (2)

• Characterize the de Novo Molecular Mutation Profile of the Melanomas for Association Between Objective Responses to MLN8237 in Patients With Pre-treatment Melanoma Tissue.

  At 24 weeks

• Correlation Between MLN8237-induced Selective Aurora Kinase A Inhibition in Post-treatment Tumor Sites and Clinical Benefit of MLN8237

  At 24 weeks

Study Arms (1)

MLN8237

EXPERIMENTAL

Patients receive oral Aurora A kinase inhibitor MLN8237 every 12 hours on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Other: laboratory biomarker identification and analysis; Procedure: biopsy; Other: immunohistochemistry/tissue microarrays; Genetic: TdT-mediated dUTP nick end labeling assay; Other: mass spectrometry

Interventions

laboratory biomarker identification and analysis OTHER

Correlative studies

Also known as: protein expresssion analysis

MLN8237

biopsy PROCEDURE

Correlative studies

Also known as: selective tissue excision

MLN8237

immunohistochemistry/tissue microarrays OTHER

Correlative studies

MLN8237

TdT-mediated dUTP nick end labeling assay GENETIC

Correlative studies

Also known as: TUNEL assay

MLN8237

mass spectrometry OTHER

Correlative studies

MLN8237

Eligibility Criteria

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

You may qualify if:

• Stage IIIc or IV histologically proven melanoma (confirmed by Vanderbilt pathologists), that is not curable by standard surgery, radiation therapy, or chemotherapy. No available effective therapy (i.e.; therapy known to be curative,). Non-biopsied (resected) tumor sites must be measurable for therapy.
• Patients on stage 2 of the enrollment must have tumor sites that are easily biopsied and be willing to undergo pre- and post-treatment (around day 8 +/- 3 days) tumor biopsies.
• Adequate performance status for the study, ECOG 0-1
• Adequate baseline organ system function, including
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 without growth factor support
• Hemoglobin ≥ 9.0g/dL (without need for transfusion support within 30 days; growth factor allowed)
• Platelet count ≥100,000 cells/mm3 without transfusion or growth factor requirement
• INR\<1.5,
• Creatinine \< 1.5x institutional upper limit of normal (IULN), and/or an adequate renal function as defined by: Calculated creatinine clearance must be ≥ 40 mL/minute (Cockcroft-Gault).
• Aspartate and alanine aminotransferase \< 2.5 x institutional upper limit of normal (IULN), bilirubin \< 1.5x IULN
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for 3 months after the completion of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study and for 3 months after the completion of the study
• A single regimen of prior chemotherapy for metastatic melanoma is allowed. Patients also may have received other immunotherapy or biologic therapy (including kinase inhibitors, antibodies to checkpoints CTLA4, PD1, PDL1, etc.) for metastatic melanoma and there is a limit of three therapy regimens
• No prior Aurora kinase inhibitor
• Completed prior chemotherapy a minimum of 4 weeks previously (6 weeks for BCNU and/or mitomycin C), 4 weeks for prior immune therapy, 6 weeks for antibodies to checkpoints CTLA4, PD1, PDL1, etc, and 2 weeks for targeted agents (i.e. inhibitors of MEK, BRAF, Akt, PI3K, mTORC1/2) or localized radiation therapy. All treatment All treatment related toxicity must have resolved to grade 2 or less or to a baseline level as well.
• Patients cannot receive concomitant radiation therapy at enrollment. While on protocol limited palliative radiotherapy extending over a small bone marrow field (10%) is allowed.

You may not qualify if:

• Uncontrolled or serious infection
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Patients with thromboembolic disease cannot be on coumadin, but low molecular heparins are allowed.
• Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
• Prior allogeneic bone marrow or organ transplantation.
• Concurrent therapy for cancer.
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
• Inability to comply with protocol-specified procedures (i.e., treatment, monitoring, or follow-up)
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Patients with GI absorptive problems making it unlikely to absorb study medication or more likely to experience GI toxicities.
• Patient is HIV-positive and is receiving combination antiretroviral therapy.
• Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine 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
• Other serious medical problem that in the view of the investigator makes therapy difficult to comply with or difficult to interpret toxicity
• If applicable, patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

Related Links

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

MeSH Terms

Conditions

Melanoma

Interventions

Biopsy; Immunohistochemistry; Mass Spectrometry

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Histocytochemistry; Histological Techniques; Immunologic Techniques; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Jeff Sosman, MD
• Organization: Vanderbilt-Ingram Cancer Center

jeff.sosman@vanderbilt.edu

615-875-8359

Study Officials

• Jeffrey Sosman, MD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine; Director, Melanoma and Tumor Immunotherapy

Study Record Dates

• First Submitted: March 15, 2011
• First Posted: March 16, 2011
• Study Start: October 1, 2011
• Primary Completion: November 1, 2014
• Study Completion: August 1, 2015
• Last Updated: May 30, 2016
• Results First Posted: May 30, 2016

Record last verified: 2016-04

Locations

US (1)