MLN8237 and Pazopanib in Combination for Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Illinois at Chicago
Sponsor:
Information provided by (Responsible Party):
Arkadiusz Dudek, MD, University of Illinois at Chicago
ClinicalTrials.gov Identifier:
NCT01639911
First received: March 26, 2012
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

This phase I dose escalation study will evaluate alisertib, an Aurora A kinase inhibitor, when given in combination with the selective vascular endothelial growth factor receptor (VEGFR) inhibitor pazopanib in patients with advanced, previously treated non-hematologic solid tumors.


Condition Intervention Phase
Malignant Neoplasm of Breast
CNS Malignancy
Malignant Neoplasm of Gastrointestinal Tract
Genitourinary Neoplasms Malignancy and Gender Unspecified
Head and Neck Neoplasms
Melanoma
Malignant Neoplasm of Thorax
Drug: Alisertib
Drug: Pazopanib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Aurora A Kinase Inhibitor (MLN8237) Given in Combination With Selective VEGFR Inhibitor Pazopanib (Votrient) for Therapy in Solid Tumors

Resource links provided by NLM:


Further study details as provided by University of Illinois at Chicago:

Primary Outcome Measures:
  • Optimally Tolerated Dose [ Time Frame: At end of Cycle 1 (approximately Day 21) ] [ Designated as safety issue: Yes ]
    Complete all planned treatment for cycle 1 (defined as 14 doses of alisertib and daily pazopanib) without dose limiting toxicity and are able to start cycle 2 with no more than a 2 week delay.


Secondary Outcome Measures:
  • Toxicity Profile [ Time Frame: Within 30 days of Last Treatment Dose ] [ Designated as safety issue: Yes ]
    Adverse events which occur after taking at least one dose of study treatment with either alisertib and/or pazopanib.


Estimated Enrollment: 30
Study Start Date: August 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treated Patients with Solid Tumor
Alisertib at the assigned dose (10, 20, 40 or 50 mg) by mouth PO twice a day for 7 days beginning on day 1 of a 21 day cycle. Pazopanib at the assigned dose (400, 600 or 800 mg) by mouth (PO) once a day beginning on day 10 of the 1st cycle and continuing daily for the duration of study treatment.
Drug: Alisertib
Alisertib at the assigned (10, 20, 40 or 50 mg) dose by mouth (PO) twice a day for 7 days beginning on day 1 of a 21 day cycle.
Other Name: MLN8237
Drug: Pazopanib
Pazopanib at the assigned dose (400, 600 or 800 mg) by mouth (PO) once a day beginning on day 10 of the 1st cycle and continuing daily for the duration of study treatment.
Other Name: Votrient

Detailed Description:

Alisertib is taken orally twice a day for the 1st 7 days of a 21 day cycle. Pazopanib is taken orally once a day continuously beginning on day 10 of cycle 1 to allow for alisertib pharmacokinetics (PKs). Treatment continues until disease progression, unacceptable toxicity, or patient refusal. PKs will be done on all patients in association with the last dose of alisertib cycles 1 and 2.

  Eligibility

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

Inclusion Criteria:

  • Diagnosis of advanced non-hematologic solid tumor malignancy that has failed/become intolerant to standard therapy
  • Measurable disease per RECIST
  • Age ≥ 18 years
  • ECOG performance status of 0-2
  • Prior systemic chemotherapy, immunotherapy, or biological therapy is allowed; however prior use of study drugs in combination is not allowed.
  • Must have recovered from the reversible effects of previous anti-cancer treatment
  • Adequate organ function within 14 days of study registration
  • Patient must be able to take oral medication and to maintain a fast as required for 2 hrs before and 2 hrs after alisertib admin.
  • Subjects agrees to use contraception, as needed

Exclusion Criteria:

  • Untreated or symptomatic CNS metastases
  • Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is excluded.
  • Prior allogeneic bone marrow transplantation
  • >or = Grade 2 peripheral neuropathy within 14 days before enrollment
  • Known history of uncontrolled sleep apnea & other conditions that could result in excessive daytime sleepiness
  • Requirement for constant admin. of proton pump inhibitor, H2 antagonist, or pancreatic enzymes.
  • Systemic infection requiring IV antibiotics within 14 days preceding the 1st dose of study drug, or other severe infection.
  • MI within 6 mos. prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, CVA, pulmonary embolism or untreated DVT or evidence of acute ischemia or active conduction system abnormalities on ECG (e.g., repeated demonstration of QTc interval > 450 msec)
  • Pregnant or breast-feeding.
  • Patient has received other investigational drugs with 14 days
  • Serious medical/psychiatric illness in the opinion of the PI would likely interfere with participation
  • 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.
  • 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
  • Known history of HIV infection, hepatitis B, or hepatitis C.
  • Recent (within 6 months) arterial thromboembolic events, including TIA, CVA, unstable angina, or MI. Pts. with clinically significant PAD are ineligible.
  • History of thrombotic or hemorrhagic disorders, not receiving chronic daily treatment with ASA (>325 mg/day) or NSAIDs known to inhibit platelet function. Treatment with dipyridamole (persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal).
  • History of abdominal fistula, GI perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment
  • Clinically significant GI abnormalities that may affect absorption of IP including, but not limited to:

    • Ongoing nausea or vomiting of any severity
    • > grade 1 diarrhea
    • Malabsorption syndrome
    • Major resection of stomach or small bowel
  • Inability to swallow oral medications or inability to take nothing by mouth except water and prescribed medications for 2 hrs before and 2 hrs after each dose of alisertib.
  • Poorly controlled HTN [SBP of ≥140 mmHg or DBP of ≥ 90mmHg].
  • Prior major surgery/trauma within 28 days or presence of any non-healing wound, fracture, or ulcer
  • Evidence of active bleeding
  • Known endobronchial lesions or involvement of large pulmonary vessels by tumor or centrally located pulmonary cavitating lesion
  • Hemoptysis within 6 weeks
  • Unable or unwilling to D/C use of prohibited medications for at least 14 days prior to the 1st dose of study drug and for the duration of the study
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to pazopanib or alisertib
  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: NCT01639911

Contacts
Contact: Arkadiusz Z. Dudek, M.D. 312-413-8878 adudek@uic.edu

Locations
United States, Illinois
University of Illinois Cancer Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Arkadiusz Z. Dudek, M.D.    312-413-8878    adudek@uic.edu   
Contact: Williams Alisha, RN    (312) 413-2746    alishaw@uic.edu   
Principal Investigator: Arkadiusz Z. Dudek, M.D.         
Sponsors and Collaborators
University of Illinois at Chicago
Investigators
Principal Investigator: Arkadiusz Z. Dudek, M.D. University of Illinois at Chicago
  More Information

No publications provided

Responsible Party: Arkadiusz Dudek, MD, Professor, University of Illinois at Chicago
ClinicalTrials.gov Identifier: NCT01639911     History of Changes
Other Study ID Numbers: 2011LS054, X14011
Study First Received: March 26, 2012
Last Updated: January 6, 2014
Health Authority: United States: Food and Drug Administration
United States: UIC Data & Safety Monitoring Committee

Keywords provided by University of Illinois at Chicago:
malignant solid tumor
advanced non-hematologic

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Digestive System Neoplasms
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Melanoma
Thoracic Neoplasms
Urogenital Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Digestive System Diseases
Gastrointestinal Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Nervous System Neoplasms
Nervous System Diseases

ClinicalTrials.gov processed this record on July 29, 2014