Clinical Trial: NCT01339871 - My Cancer Genome

NCT01339871

Description:

The goal of this clinical research study is to find the highest tolerable dose of the combination of pazopanib and vorinostat that can be given to patients with advanced cancer. The safety of the drug combination will also be studied.

Related Conditions:

Leukemia
Lymphoma
Malignant Solid Tumor

Recruiting Status:

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT01339871

Trial Eligibility

Document

Title

Brief Title: Study of Pazopanib and Vorinostat in Patients With Advanced Malignancies
Official Title: A Phase I Study of Pazopanib and Vorinostat in Patients With Advanced Malignancies

Clinical Trial IDs

ORG STUDY ID: 2011-0051
SECONDARY ID: NCI-2011-00771
NCT ID: NCT01339871

Conditions

Advanced Cancer

Interventions

Drug	Synonyms	Arms
Pazopanib	GW786034	Pazopanib + Vorinostat
Vorinostat	SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza	Pazopanib + Vorinostat

Purpose

Detailed Description

      Study Drugs:

      Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for
      tumor growth. This may prevent or slow the growth of cancer cells.

      Vorinostat is designed to cause chemical changes in different groups of proteins that are
      attached to DNA (the genetic material of cells), which may slow the growth of cancer cells or
      cause the cancer cells to die.

      Study Groups:

      If you are found to be eligible to take part in this study, up to 12 dose levels of pazopanib
      and vorinostat will be tested. Three (3) to 6 participants will be enrolled at each dose
      level of the combination of pazopanib and vorinostat. The first group of participants will
      receive the lowest dose level of pazopanib and vorinostat. Each new group(s) will receive a
      higher combination dose of pazopanib and vorinostat than the group before it, if no
      intolerable side effects were seen. Participants may be enrolled on 1-3 similar dose levels
      of pazopanib and vorinostat at the same time. You will be assigned to a dose level based on
      when you joined this study. This will continue until the highest tolerable dose(s) of the
      study drug combination is found.

      The dose of the study drug combination that you receive may be lowered if you have
      intolerable side effects.

      Once the highest tolerable dose of pazopanib and vorinostat is found, this combination dose
      will be given to an expansion group of 14 additional participants.

      Study Drug Administration:

      You will take pazopanib and vorinostat by mouth 1 time each day. Note that you will not take
      the study drugs at the same time as each other. You should take pazopanib either 1 hour
      before or 2 hours after eating a meal. You should take vorinostat with food.

      Study Visits:

      Each study cycle is 28 days.

      At all study visits, you will be asked about any drugs you may be taking and side effects you
      may be having.

      If you are able to take your blood pressure at home, you will be asked to take your blood
      pressure each day while you are participating on this study.

      Within 7 days before the first dose of study drugs:

        -  You will have a physical exam, including measurement of your weight and vital signs
           (blood pressure, heart rate, temperature, and breathing rate).

        -  You will be asked how well you are able to perform the normal activities of daily living
           (performance status).

        -  Blood (about 2 teaspoons) and urine will be collected for routine tests.

        -  If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine
           pregnancy test.

      Every week during Cycle 1, blood (about 1 teaspoon) will be drawn for routine tests.

      During Week 1 of each cycle:

        -  Your medical history will be recorded.

        -  You will have a physical exam, including measurement of your weight and vital signs.

        -  Your performance status will be recorded.

        -  Blood (about 2 teaspoons) and urine will be collected for routine tests.

      At the end of Cycle 2 and then every 2-3 cycles after that:

        -  You will have a CT, MRI, positron emission tomography (PET) scan, and/or x-ray to check
           the status of the disease.

        -  If the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to
           measure tumor markers.

      After Cycle 6, you are only required to visit MD Anderson every 2 cycles if you get your
      blood draws at your local doctor at the beginning of each cycle. Talk to the study staff
      about this option.

      Length of Study:

      You may continue taking the study drugs for as long as the doctor thinks it is in your best
      interest. You will be taken off study early if the disease gets worse, or you have
      intolerable side effects.

      Your participation on the study will be over once you have completed the end-of-study visit.

      End-of-Study Visit:

      Within 30 days after your last dose of study drugs, you will have an end-of-study visit. At
      this visit, the following tests and procedures performed:

        -  Your medical history will be recorded.

        -  You will have a physical exam, including measurement of your weight and vital signs.

        -  Your performance status will be recorded.

        -  Blood (about 2 teaspoons) and urine will be collected for routine tests.

        -  If the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to
           measure tumor markers.

        -  If the study doctor thinks it is needed, you will have a chest x-ray, CT, MRI, and/or
           PET scan to check the status of the disease.

      Up to 174 evaluable patients will take part in this study. All will be enrolled at MD
      Anderson.

Trial Arms

Name	Type	Description	Interventions
Pazopanib + Vorinostat	Experimental	Starting doses Pazopanib 400 mg orally daily and Vorinostat 100 mg orally daily	Pazopanib Vorinostat

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with advanced cancer, either refractory to standard therapy or for which no
             effective standard therapy that increases survival for at least 3 months is available.

          2. Patients must have measurable or evaluable disease, as defined by RECIST 1.1.

          3. Men or women aged >/= 18 years. However, patients who are 13 years old or older and
             have more than 45 kg of body weight will be eligible after consultation with their
             pediatric attending since the doses of these agents are the fixed doses.

          4. Women of child-bearing potential and men must agree to use adequate contraception.

          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

          6. Adequate organ functions: Neutrophils > 1000/uL, Platelets >/= 75,000/uL, Total
             bilirubin </= 2 x upper limit of normal (ULN) (upper limit of normal), ALT </= 2.5 x
             ULN or </= 5 x ULN if liver metastases persist, Serum creatinine < 2 x ULN

          7. Patients with either previous vascular endothelial growth factor (VEGF) inhibition
             based treatment or previous vorinostat based treatment are eligible. However, patients
             who received both VEGF and histone deacetylase (HDAC) inhibition simultaneously are
             ineligible.

          8. Specific to the cohorts as designed to enroll patients with TP53 mutations: TP53
             mutations are identified by next-generation sequencing in a chemiluminescence
             immunoassay analyzer (CLIA)-certified laboratory prior to screening.

        Exclusion Criteria:

          1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection requiring intravenous antibiotics, symptomatic congestive heart failure
             (NYHA Class III or IV), or unstable angina pectoris.

          2. Inadequately controlled hypertension (defined as systolic blood pressure >or = 140
             and/or diastolic blood pressure > or = 90 mmHg on antihypertensive medications), any
             prior history of hypertensive crisis or hypertensive encephalopathy, and history of
             myocardial infarction or unstable angina within 6 months prior to study enrollment.

          3. History of stroke or transient ischemic attack within 6 months prior to study
             enrollment.

          4. Major surgical procedure within 28 days prior to study enrollment.

          5. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to study enrollment.

          6. History of allergic reactions to the study drugs, their analogs or any component of
             the products.

          7. Any treatment specific for tumor control within 3 weeks of study drugs; or within 2
             weeks if cytotoxic agents were given weekly (within 6 weeks for nitrosoureas or
             mitomycin C), or within 5 half-lives for targeted agents with half lives and
             pharmacodynamic effects lasting less than 5 days (that includes but is not limited to
             erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents). Palliative
             radiation immediately before or during the study is acceptable provided there is
             evaluable disease that has not been radiated.

          8. Urine for proteinuria >/= 2+ (patients discovered to have >/= 2+ proteinuria on
             urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate
             </= 1g of protein in 24 hours to be eligible).

          9. Patients with clinical bleeding, active gastric or duodenal ulcer.

         10. Symptomatic primary tumors or metastasis of brain and/or central nervous system that
             are uncontrolled with antiepileptics and requiring high doses of steroids.

         11. Concurrent use of antiarrythmics or contraindicated medications (including, but not
             limited to, cisapride, mesoridazine, pimozide, posaconazole, sparfloxacin,
             thioridazine).

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Maximum tolerated dose (MTD) of Pazopanib and Vorinostat
Time Frame:	28 days
Safety Issue:
Description:	Maximum tolerated dose defined by dose limiting toxicities (DLTs) that occur in the first 28 days. . Non-hematological toxicities are graded by using NCI CTCAE v4.0 toxicity criteria and DLT defined as treatment-related grade 3 or greater non-hematological toxicity other than nausea, vomiting, fatigue, or hypertension, drug-related grade 3 or greater electrolyte abnormalities that do not return to ≤ grade 1 or baseline within 72 hours, grade 3 nausea and vomiting related to study drug treatment that is not controlled at 72 hours despite appropriate antiemetic therapy, or grade 4 fatigue or hypertension related to study drug therapy.

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Completed
Lead Sponsor:	M.D. Anderson Cancer Center

Trial Keywords

Pazopanib
Vorinostat
Advanced Malignancies

Last Updated

June 16, 2017

Clinical Trials /

Study of Pazopanib and Vorinostat in Patients With Advanced Malignancies