NCT01339871

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
152

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Apr 2011

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 20, 2011

Completed
Same day until next milestone

Study Start

First participant enrolled

April 20, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 21, 2011

Completed
6.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 7, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 7, 2017

Completed
Last Updated

June 16, 2017

Status Verified

June 1, 2017

Enrollment Period

6.1 years

First QC Date

April 20, 2011

Last Update Submit

June 14, 2017

Conditions

Advanced Cancer

Keywords

PazopanibVorinostatAdvanced Malignancies

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose (MTD) of Pazopanib and Vorinostat

    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.

    28 days

Study Arms (1)

Pazopanib + Vorinostat

EXPERIMENTAL

Starting doses Pazopanib 400 mg orally daily and Vorinostat 100 mg orally daily

Drug: PazopanibDrug: Vorinostat

Interventions

PazopanibDRUG

Starting dose 400 mg orally daily of 28 day cycle.

Also known as: GW786034
Pazopanib + Vorinostat
VorinostatDRUG

Starting dose 100 mg orally daily of 28 day cycle.

Also known as: SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza
Pazopanib + Vorinostat

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  • 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
  • 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.
  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

  • Fu S, Hou MM, Naing A, Janku F, Hess K, Zinner R, Subbiah V, Hong D, Wheler J, Piha-Paul S, Tsimberidou A, Karp D, Araujo D, Kee B, Hwu P, Wolff R, Kurzrock R, Meric-Bernstam F. Phase I study of pazopanib and vorinostat: a therapeutic approach for inhibiting mutant p53-mediated angiogenesis and facilitating mutant p53 degradation. Ann Oncol. 2015 May;26(5):1012-1018. doi: 10.1093/annonc/mdv066. Epub 2015 Feb 10.

    PMID: 25669829DERIVED

Related Links

MeSH Terms

Interventions

pazopanibVorinostat

Intervention Hierarchy (Ancestors)

AnilidesAmidesOrganic ChemicalsAniline CompoundsAminesHydroxamic AcidsHydroxylaminesHydroxy AcidsCarboxylic Acids

Study Officials

  • Siqing Fu, MD,PHD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 20, 2011

First Posted

April 21, 2011

Study Start

April 20, 2011

Primary Completion

June 7, 2017

Study Completion

June 7, 2017

Last Updated

June 16, 2017

Record last verified: 2017-06

Locations

US(1)