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Malignant Neoplasm of BreastPhase 1NCT01639911

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

A Phase 1 study testing Alisertib and Pazopanib in people with Malignant Neoplasm of Breast and CNS Malignancy, run by University of Illinois Chicago at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Alisertib and Pazopanib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteUnited States
Study dates
14 Aug 2013to 28 Jul 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.
  • Patient must be able to take oral medication and to maintain a fast as required for 2 hrs before and 2 hrs after alisertib administration
  • Female patient is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for 4 months after the last dose of alisertib.
  • Male patient agrees to use an acceptable method for contraception during the entire study treatment period through 4 months after the last dose of alisertib.
  • Voluntary written consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

Who cannot join

  • 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.
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  • 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.
  • Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinical significant or baseline prolongation of the rate-corrected QT interval (e.g., repeated demonstration of QTc interval > 450 milliseconds)
  • Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg]. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. The mean SBP / DBP values from each blood pressure assessment must be < 140/90mmHg in order for a subject to be eligible for the study.
  • History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible. Patients receiving Coumadin must be transition to low molecular weight heparin and treated for at least 14 days prior to the first dose of study drug.
  • Presence of any non-healing wound, fracture, or ulcer within 28 days prior to the first dose of study drug
  • Evidence of active bleeding or bleeding diathesis
  • Known endobronchial lesions or involvement of large pulmonary vessels by tumor or centrally located pulmonary cavitating lesion
  • Hemoptysis (> ½ teaspoon of bright red blood per episode) within 6 weeks of first dose of study drug
  • Unable or unwilling to discontinue use of prohibited medications list in Section 6.5 for at least 14 days prior to the first dose of study drug and for the duration of the study
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or alisertib

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Illinois Cancer Center

    Chicago, Illinois, 60612

Other trials in United States

About this study

Official title: STM-01: Phase I EffTox Study of Aurora A Kinase Inhibitor Alisertib (MLN8237) Given in Combination With Selective VEGFR Inhibitor Pazopanib (Votrient) for Therapy of Solid Tumors

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.

Being tested
Alisertib, Pazopanib
Keywords
malignant solid tumor, advanced non-hematologic
Medical subject headings
Breast Neoplasms, Central Nervous System Neoplasms, Gastrointestinal Neoplasms, Head and Neck Neoplasms, Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlisertibDrug

    Also called MLN8237

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

  • PazopanibDrug

    Also called Votrient

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

Study groups in NCT01639911
Study groupRoleWhat they receive
Treated Patients with Solid TumorExperimentalPatients 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.
Receives: Drug: Alisertib; Drug: Pazopanib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At end of Cycle 1 (approximately Day 21)

Secondary outcomes (1)

  1. Toxicity Profile

    Adverse events which occur after taking at least one dose of study treatment with either alisertib and/or pazopanib.

    Measured: Within 30 days of Last Treatment Dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2012 (estimated)
  2. Study start14 Aug 2013
  3. Primary completion28 Jul 2016
  4. Study completion28 Jul 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01639911
Sponsor's protocol ID
2013-0100
Other IDs
X14011, 2013-0100
Status last verified
Jul 2019
First submitted
26 Mar 2012
Last updated
22 Jul 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes

Publications

  • 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.

    PubMed 30973373

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Alisertib and Pazopanib in people with Malignant Neoplasm of Breast and CNS Malignancy, run by University of Illinois Chicago at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Optimally Tolerated Dose (time frame: At end of Cycle 1 (approximately Day 21)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01639911, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2019.

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