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

NCT00495872 | Completed Phase 1

• 1 other identifier: 2007-0170
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumors

Keywords

Solid Tumors; Advanced Cancer; Dasatinib; Erlotinib; Lapatinib; Lenalidomide; Sorafenib; Erlotinib Hydrochloride; Sunitinib Malate; Sunitinib; Valproic Acid; SU011248

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities

  At Day 28 (1 Cycle)

Study Arms (6)

VN

EXPERIMENTAL

Valproic Acid + Sorafenib

Drug: Sorafenib; Drug: Valproic Acid

VS

EXPERIMENTAL

Valproic Acid + Sunitinib

Drug: Sunitinib; Drug: Valproic Acid

VD

EXPERIMENTAL

Valproic Acid + Dasatinib

Drug: Dasatinib; Drug: Valproic Acid

VT

EXPERIMENTAL

Valproic Acid + Erlotinib

Drug: Erlotinib; Drug: Valproic Acid

VL

EXPERIMENTAL

Valproic Acid + Lapatinib

Drug: Lapatinib; Drug: Valproic Acid

VR

EXPERIMENTAL

Valproic Acid + Lenalidomide

Drug: Lenalidomide; Drug: Valproic Acid

Interventions

Dasatinib DRUG

50 mg by mouth (PO) Twice Daily for 28 Days Every 28 Days

Also known as: Sprycel®, BMS-354825

VD

Erlotinib DRUG

100 mg PO Daily for 28 Days Every 28 Days

Also known as: Erlotinib Hydrochloride, OSI-774, Tarceva

VT

Lapatinib DRUG

1000 mg PO Daily for 28 Days Every 28 Days

Also known as: GW572016

VL

Lenalidomide DRUG

15 mg PO Daily for 28 Days Every 28 Days

Also known as: CC-5013, Revlimid™

VR

Sorafenib DRUG

400 mg PO Daily for 21 Days Every 28 Days

Also known as: BAY 43-9006

VN

Sunitinib DRUG

25 mg PO Daily for 21 Days Every 28 Days

Also known as: Sunitinib Malate, SU011248

VS

Valproic Acid DRUG

40 mg/kg PO Daily for 7 Days, then 7 Days Off

Also known as: Depakene

VD; VL; VN; VR; VS; VT

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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)
• 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;
• (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);
• (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.
• 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)
• 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)

You may not qualify if:

• 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.
• History of allergic reactions to the study drugs or their analogs.
• Failure to recover from any prior surgery within 4 weeks of study entry.
• 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.
• Study agents cannot be obtained for any reason since this study does not provide free agents.
• Any prior history of hypertensive crisis or hypertensive encephalopathy.
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection) and symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy.
• 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.
• Minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Kurzrock R, Atkins J, Wheler J, Fu S, Naing A, Busaidy N, Hong D, Sherman S. Tumor marker and measurement fluctuations may not reflect treatment efficacy in patients with medullary thyroid carcinoma on long-term RET inhibitor therapy. Ann Oncol. 2013 Sep;24(9):2256-61. doi: 10.1093/annonc/mdt177. Epub 2013 May 14.

  PMID: 23676418 DERIVED

Related Links

• MD Anderson Cancer Center website

MeSH Terms

Interventions

Dasatinib; Erlotinib Hydrochloride; Lapatinib; Lenalidomide; Sorafenib; Sunitinib; Valproic Acid

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Pyrroles; Indoles; Pentanoic Acids; Valerates; Acids, Acyclic; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Aung Naing, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2007
• First Posted: July 3, 2007
• Study Start: June 1, 2007
• Primary Completion: October 1, 2012
• Last Updated: October 18, 2012

Record last verified: 2012-10

Locations

US (1)