Phase I Study of MLN8237 and Pazopanib in Patients With Solid Tumors

NCT01639911 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 2013-0100X14011
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial using the EffTox design will evaluate activity and safety of alisertib, an Aurora A kinase inhibitor, when given in combination with the selective VEGFR inhibitor pazopanib in patients with advanced, previously treated non-hematologic solid tumors.

Conditions

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

Keywords

malignant solid tumor; advanced non-hematologic

Outcome Measures

Primary Outcomes (1)

• Optimally Tolerated Dose

  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.

  At end of Cycle 1 (approximately Day 21)

Secondary Outcomes (1)

• Toxicity Profile

  Within 30 days of Last Treatment Dose

Study Arms (1)

Treated Patients with Solid Tumor

EXPERIMENTAL

Patients will receive alisertib orally twice a day for the first 7 days of a 21 day cycle. Patients will also receive pazopanib orally once a day continuously. Treatment continues until disease progression, unacceptable toxicity or patient refusal. The study consists of two components which are the dose finding component and optimally tolerated dose extension with pharmacokinetics component.

Drug: Alisertib; Drug: Pazopanib

Interventions

Alisertib DRUG

Alisertib at the assigned dose by mouth (PO) twice a day for 7 days beginning on day 1 of a 21 day cycle.

Also known as: MLN8237

Treated Patients with Solid Tumor

Pazopanib DRUG

Pazopanib at the assigned dose once a day continuously for the duration of treatment.

Also known as: Votrient

Treated Patients with Solid Tumor

Eligibility Criteria

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

You may qualify if:

• Diagnosis of advanced non-hematologic solid tumor malignancy, including, but not limited to breast, lung, colon, pancreatic, head and neck, kidney or sarcoma that has failed or become intolerant to standard therapy and is no longer likely to respond to such therapy. Note: The MTD for pazopanib monotherapy in patients with hepatocellular cancer was found to be 600 mg daily therefore enrollment for these patients will be limited to pazopanib dose levels at or below 600 mg.
• Measurable disease per RECIST version 1.1
• 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.
• Time since prior therapy and the first dose of study drug
• At least 21 days since previous antineoplastic therapy
• At least 42 days since previous nitrosoureas or mitomycin-C
• At least 42 days since exposure to fully human monoclonal antibodies
• At least 28 days since previous chimeric monoclonal antibodies
• At least 14 days since noncytotoxic small molecule drugs (eg tyrosine kinase inhibitors such as Tarceva® and hormonal agents such as Femara®)
• At least 21 days since previous radiation therapy
• At least 14 days since prior major surgery (defined as a surgery involving a risk to the life of the patient; specifically: an operation upon an organ within the cranium, chest, abdomen, or pelvic cavity)
• At least 3 months since prior autologous transplant
• Must have recovered from the reversible effects (≤ grade 1 CTCAE) of previous anti-cancer treatment prior to study registration

You may not qualify if:

• Untreated or symptomatic CNS metastases
• Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is is considered to be over 25%.
• Prior allogeneic bone marrow transplantation
• ≥ Grade 2 peripheral neuropathy within 14 days before enrollment
• Known history of uncontrolled sleep apnea and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.
• Requirement for constant admin. of proton pump inhibitor, H2 antagonist, or pancreatic enzymes. Intermittent uses of antacids or H2 antagonists are allowed as described in the protocol.
• Systemic infection requiring IV antibiotics within 14 days preceding the 1st dose of study drug, or other severe infection.
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class II, III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities requiring therapy. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Pregnant or breast-feeding. Pazopanib is Pregnancy Category D - known teratogenic potential. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Patient has received other investigational drugs with 14 days before enrollment
• Serious medical or psychiatric illness in the opinion of the researcher that would likely interfere with participation in this clinical study.
• Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
• 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 alisertib and during the study.
• Treatment should be avoided (however not prohibited) with strong UGT inhibitors such as atazanavir, gemfibrozil, indinavir, ketoconazole, Silybum marianum (milk thistle), Valeriana officinalis (garden valerian) or inducers such as carbamazepine, nicotine, Orthosiphon stamineus within 14 days prior to the first dose of alisertib and during the study.
• Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion.

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Related Publications (1)

• Shah HA, Fischer JH, Venepalli NK, Danciu OC, Christian S, Russell MJ, Liu LC, Zacny JP, Dudek AZ. Phase I Study of Aurora A Kinase Inhibitor Alisertib (MLN8237) in Combination With Selective VEGFR Inhibitor Pazopanib for Therapy of Advanced Solid Tumors. Am J Clin Oncol. 2019 May;42(5):413-420. doi: 10.1097/COC.0000000000000543.

  PMID: 30973373 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Central Nervous System Neoplasms; Gastrointestinal Neoplasms; Head and Neck Neoplasms; Melanoma

Interventions

MLN 8237; pazopanib

Condition Hierarchy (Ancestors)

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

Study Officials

• Arkadiusz Z. Dudek, M.D.

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 26, 2012
• First Posted: July 13, 2012
• Study Start: August 14, 2013
• Primary Completion: July 28, 2016
• Study Completion: July 28, 2016
• Last Updated: July 22, 2019

Record last verified: 2019-07

Locations

US (1)