MLN8237 and Pazopanib in Combination for Solid Tumors
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
Conditions: official terms
Breast Neoplasms - Digestive System Neoplasms - Gastrointestinal Neoplasms - Head and Neck Neoplasms - Neoplasms - Thoracic Neoplasms - Urogenital Neoplasms
Conditions: Keywords
malignant solid tumor, advanced non-hematologic
Study Type
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: Alisertib Type: Drug
Name: Pazopanib Type: Drug
Overall Status
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.
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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 PS 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 tx

- 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 BMT

- >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 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
University of Illinois Cancer Center
Chicago, Illinois, United States
Status: Recruiting
Contact: Arkadiusz Z. Dudek, M.D. - 312-413-8878 -
Start Date
August 2013
Completion Date
September 2016
University of Illinois at Chicago
University of Illinois at Chicago
Record processing date processed this data on July 28, 2015 page