Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Phase I Study of Pazopanib and Vorinostat

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center Identifier:
First received: April 20, 2011
Last updated: December 27, 2016
Last verified: December 2016
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.

Condition Intervention Phase
Advanced Cancer
Drug: Pazopanib
Drug: Vorinostat
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Pazopanib and Vorinostat in Patients With Advanced Malignancies

Resource links provided by NLM:

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of Pazopanib and Vorinostat [ Time Frame: 28 days ]
    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.

Estimated Enrollment: 174
Study Start Date: April 2011
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pazopanib + Vorinostat
Starting doses Pazopanib 400 mg orally daily and Vorinostat 100 mg orally daily
Drug: Pazopanib
Starting dose 400 mg orally daily of 28 day cycle.
Other Name: GW786034
Drug: Vorinostat
Starting dose 100 mg orally daily of 28 day cycle.
Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza

  Show Detailed Description


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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. ECOG performance status of 0 to 2.
  6. Adequate organ functions: Neutrophils > 1000/uL, Platelets >/= 75,000/uL, Total bilirubin </= 2 x 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 VEGF inhibition based treatment or previous vorinostat based treatment are eligible. However, patients who received both VEGF and 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 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01339871

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Principal Investigator: Siqing Fu, MD,PHD M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01339871     History of Changes
Other Study ID Numbers: 2011-0051
NCI-2011-00771 ( Registry Identifier: NCI CTRP )
Study First Received: April 20, 2011
Last Updated: December 27, 2016

Keywords provided by M.D. Anderson Cancer Center:
Advanced Malignancies

Additional relevant MeSH terms:
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on April 28, 2017