Valproic Acid-Based 2-Agent Oral Regimens for Patients With Advanced Solid Tumor

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00495872
First received: July 2, 2007
Last updated: October 16, 2012
Last verified: October 2012
  Purpose

The goal of this clinical research study is to find the highest tolerable dose of valproic acid in combination with either dasatinib, erlotinib hydrochloride, lapatinib, lenalidomide, sorafenib, or SU011248 (sunitinib malate) that can be given to patients with advanced cancer. The safety of each combination of the study drugs will be studied as well.


Condition Intervention Phase
Solid Tumors
Drug: Dasatinib
Drug: Erlotinib
Drug: Lapatinib
Drug: Lenalidomide
Drug: Sorafenib
Drug: Sunitinib
Drug: Valproic Acid
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Arm Complete Phase 1 Trial of Valproic Acid-Based 2-Agent Oral Regimens for Patients With Advanced Solid Tumor

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities [ Time Frame: At Day 28 (1 Cycle) ] [ Designated as safety issue: Yes ]

Enrollment: 204
Study Start Date: June 2007
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VN
Valproic Acid + Sorafenib
Drug: Sorafenib
400 mg PO Daily for 21 Days Every 28 Days
Other Name: BAY 43-9006
Drug: Valproic Acid
40 mg/kg PO Daily for 7 Days, then 7 Days Off
Other Name: Depakene
Experimental: VS
Valproic Acid + Sunitinib
Drug: Sunitinib
25 mg PO Daily for 21 Days Every 28 Days
Other Names:
  • Sunitinib Malate
  • SU011248
Drug: Valproic Acid
40 mg/kg PO Daily for 7 Days, then 7 Days Off
Other Name: Depakene
Experimental: VD
Valproic Acid + Dasatinib
Drug: Dasatinib
50 mg by mouth (PO) Twice Daily for 28 Days Every 28 Days
Other Names:
  • Sprycel®
  • BMS-354825
Drug: Valproic Acid
40 mg/kg PO Daily for 7 Days, then 7 Days Off
Other Name: Depakene
Experimental: VT
Valproic Acid + Erlotinib
Drug: Erlotinib
100 mg PO Daily for 28 Days Every 28 Days
Other Names:
  • Erlotinib Hydrochloride
  • OSI-774
  • Tarceva
Drug: Valproic Acid
40 mg/kg PO Daily for 7 Days, then 7 Days Off
Other Name: Depakene
Experimental: VL
Valproic Acid + Lapatinib
Drug: Lapatinib
1000 mg PO Daily for 28 Days Every 28 Days
Other Name: GW572016
Drug: Valproic Acid
40 mg/kg PO Daily for 7 Days, then 7 Days Off
Other Name: Depakene
Experimental: VR
Valproic Acid + Lenalidomide
Drug: Lenalidomide
15 mg PO Daily for 28 Days Every 28 Days
Other Names:
  • CC-5013
  • Revlimid™
Drug: Valproic Acid
40 mg/kg PO Daily for 7 Days, then 7 Days Off
Other Name: Depakene

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have advanced solid tumor: they have either a disease where there is no established standard of care therapy or have failed one or more prior therapy. (for all treatment arms)
  2. Patients must have ECOG performance status < or = 2 (0-2). Patients </=10 years modified Lansky scale >/= 60. Patients >10 to 18 years Karnovsky scale >/= 60.(for all treatment arms)
  3. Patients must have normal organ and marrow function as defined below: Platelets > 50,000/uL; Creatinine clearance > 20mL/min (for all treatment arms); Total bilirubin < 5 mg/dL (except for Lapatinib arm); ALT </= 6X ULN for Lapatinib arm only;
  4. (cont. from above) Liver function criteria and dosing based on each individual drug: Valproic acid - if ALT >/= 6X ULN or T. Bili >/= 3, then dose should be decreased by 50%; Sorafenib - If Child Pugh class A or B, no dose adjustment; if Child Pugh class C, decrease dose by 50% (400 mg po daily max); Sunitinib - If ALT >/= 6X ULN or T. Bili >/= 3 , decrease dose by 25% (37.5 mg po daily max);
  5. (cont. from above) Erlotinib - If ALT > 6X ULN or T. Bili >/= 3 , decrease dose by 25% (100 mg po daily max); Lapatinib - If ALT > 3X ULN or T. Bili > 2X ULN, decrease dose by 60% (500-750 mg po daily max); Dasatinib - No dose adjustment needed; Lenalidomide - No dose adjustment needed.
  6. Patients or legal representative must be able to understand and be willing to sign an IRB-approved written informed consent document. (for all treatment arms)
  7. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose. (for all treatment arms)

Exclusion Criteria:

  1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, symptomatic cardiac arrhythmia, active bleeding, active thrombosis, or psychiatric illness/social situations that would limit compliance with study requirements.
  2. History of allergic reactions to the study drugs or their analogs.
  3. Failure to recover from any prior surgery within 4 weeks of study entry.
  4. 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 4 half-lives for target agents with half lives and pharmacodynamic effects lasting less than 5 days (that include but are not limited to erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents); or failure to recover from the toxic effect of any therapy prior to study entry.
  5. Study agents cannot be obtained for any reason since this study does not provide free agents.
  6. Any prior history of hypertensive crisis or hypertensive encephalopathy.
  7. Significant vascular disease (e.g., aortic aneurysm, aortic dissection) and symptomatic peripheral vascular disease
  8. Evidence of bleeding diathesis or coagulopathy.
  9. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study.
  10. Minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment.
  11. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment; and serious, non-healing wound, ulcer, or bone fracture.
  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 ClinicalTrials.gov identifier: NCT00495872

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Aung Naing, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided by M.D. Anderson Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00495872     History of Changes
Other Study ID Numbers: 2007-0170
Study First Received: July 2, 2007
Last Updated: October 16, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Solid Tumors
Advanced Cancer
Dasatinib
Erlotinib
Lapatinib
Lenalidomide
Sorafenib
Erlotinib Hydrochloride
Sunitinib Malate
Sunitinib
Valproic Acid
SU011248

Additional relevant MeSH terms:
Neoplasms
Valproic Acid
Erlotinib
Sorafenib
Dasatinib
Lapatinib
Lenalidomide
Sunitinib
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Protein Kinase Inhibitors
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014