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

Completed · Phase 1

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT01639911

Run by

University of Illinois at Chicago

People needed

28

Starts

2013-08-14

Expected to finish

2016-07-28

Last updated by the study team

2019-07-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• Adequate organ function within 14 days of study registration defined as:
• Absolute neutrophil count (ANC) > 1500/mm\^3
• Hemoglobin > 9 g/dL (Values must be obtained without need for myeloid growth factor or platelet transfusion support within 14 days, however, erythrocyte growth factor is allowed as per published ASCO guidelines)
• Platelets > 100,000/mm\^3 (Values must be obtained without need for myeloid growth factor or platelet transfusion support within 14 days, however, erythrocyte growth factor is allowed as per published ASCO guidelines)
• Total bilirubin Within normal limits
• SGOT (AST) and SGPT (ALT) ≤1.5 X ULN
• If liver metastases present: Total bilirubin Within normal limits and SGOT (AST) and SGPT (ALT) ≤ 3.0 X ULN
• Glomerular filtration rate (GFR) ≥ 40 mL/minute
• Urine dipstick for proteinuria < 1+ within 1 week prior to registration (If urine dipstick ≥ 1, then a 24-hour urine protein must demonstrate ≤ 1 gram protein in 24 hours to participate in study)
• NOTE: Patients with liver metastases will be allowed to participate with SGOT (AST) and SGPT (ALT) of up to 3.0 times the upper limits of normal.

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.
• Recent (within 6 months) arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or myocardial infarction (MI). Patients with clinically significant peripheral artery disease are ineligible.
• History of thrombotic or hemorrhagic disorders, not receiving chronic daily treatment with aspirin (>325 mg/day) or non-steriodal anti-inflammatory agents know to inhibit platelet function. Treatment with dipyridamole (persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal).
• Use of simvastatin is not recommended but not prohibited. The concomitant use of pazopanib and simvastatin increases the risk of ALT elevations. Discontinue simvastatin if possible to decrease risk of transaminases elevation from pazopanib. There are insufficient data available to assess the risk of alternative statins. If it must be continued, monitor liver function closely and follow dosing guidelines.
• History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product 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 hours before and 2 hours after each dose of alisertib.

Where it is running

• University of Illinois Cancer Center — Chicago, Illinois, United States

Full record on ClinicalTrials.gov

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