Phase I Study of Pazopanib and Vorinostat
Verified September 2014 by M.D. Anderson Cancer Center
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
First received: April 20, 2011
Last updated: September 5, 2014
Last verified: September 2014
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.
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase I Study of Pazopanib and Vorinostat in Patients With Advanced Malignancies
Primary Outcome Measures:
- Maximum tolerated dose (MTD) of Pazopanib and Vorinostat [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
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:
| Study Start Date:
| Estimated Primary Completion Date:
||April 2016 (Final data collection date for primary outcome measure)
Experimental: Pazopanib + Vorinostat
Starting doses Pazopanib 400 mg orally daily and Vorinostat 100 mg orally daily
Starting dose 400 mg orally daily of 28 day cycle.
Other Name: GW786034
Starting dose 100 mg orally daily of 28 day cycle.
- Suberoylanilide Hydroxamic Acid
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
- Patients must have measurable or evaluable disease, as defined by RECIST 1.1.
- 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.
- Women of child-bearing potential and men must agree to use adequate contraception.
- ECOG performance status of 0 to 2.
- 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
- 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.
- 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.
- 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.
- 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.
- History of stroke or transient ischemic attack within 6 months prior to study enrollment.
- Major surgical procedure within 28 days prior to study enrollment.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
- History of allergic reactions to the study drugs, their analogs or any component of the products.
- 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.
- 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).
- Patients with clinical bleeding, active gastric or duodenal ulcer.
- Symptomatic primary tumors or metastasis of brain and/or central nervous system that are uncontrolled with antiepileptics and requiring high doses of steroids.
- Concurrent use of antiarrythmics or contraindicated medications (including, but not limited to, cisapride, mesoridazine, pimozide, posaconazole, sparfloxacin, thioridazine).
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 ClinicalTrials.gov identifier: NCT01339871
|Contact: Siqing Fu, MD,PHD
|University of Texas MD Anderson Cancer Center
|Houston, Texas, United States, 77030 |
M.D. Anderson Cancer Center
||Siqing Fu, MD,PHD
||M.D. Anderson Cancer Center
No publications provided
||M.D. Anderson Cancer Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||April 20, 2011
||September 5, 2014
||United States: Institutional Review Board
Keywords provided by M.D. Anderson Cancer Center:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on October 23, 2014
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