Back to resultsUse of Hydralazine and Valproic Acid in Advanced Solid Tumor Malignancies
Primary Purpose
Lung Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Hydralazine and Valproic Acid: Cohort -1
Hydralazine and Valproic Acid: Cohort 0
Hydralazine and Valproic Acid: Cohort 1
Hydralazine and Valproic Acid: Cohort 2
Hydralazine and Valproic Acid: Cohort 3
Hydralazine and Valproic Acid: Cohort 4
Hydralazine and Valproic Acid: Cohort 5
Sponsored by
About this trial
This is an interventional treatment trial for Lung Cancer focused on measuring Lung Cancer, Advanced Lung Cancer, Unresectable Lung cancer, Previously treated lung cancer
Eligibility Criteria
Inclusion Criteria:
- All patients with lung cancer who have disease which has been previously treated and/or for which there is no acceptable standard treatment regimen available, and cannot be treated definitively with either surgery or radiotherapy.
- All will be appropriate candidates for treatment, and are not candidates for treatment with protocols of higher priority.
- All patients should have an ECOG/Zubrod/SWOG performance status of less than 2 at the time of the initiation of therapy
- Adequate end-organ function
- No severe comorbid disease
- Ability to provide informed consent.
- Signed Informed Consent
- ECOG/Zubrod/SWOG Performance Status less than 2
- Life expectancy greater than 8 weeks
- Male or female' age greater than 18 years
- Patients of childbearing potential must be using an effective means of contraception.
- Histologic diagnosis of lung cancer that is advanced and cannot be treated adequately by radiotherapy or surgery; or metastatic disease, and for which there is no standard chemotherapeutic option remaining or available
- All participants must have either previously received or refused standard chemotherapy
- Baseline laboratory values (bone marrow, renal, hepatic):
Adequate bone marrow function:
- Absolute neutrophil count greater than 1000/µL
- Platelet count greater than 100'000/µL
Renal function:
a. Serum creatinine less than 2.0 mg %
Hepatic function:
- Bilirubin less than 1.5x normal
- Serum calcium less than 12 mg/dl
Exclusion Criteria
- Pregnant or lactating females
- Myocardial infarction or ischemia within the 6 months before Cycle 0' Day 0
- Uncontrolled' clinically significant dysrhythmia
- Prior radiotherapy to an indicator lesion unless there is objective evidence of tumor growth in that lesion
- Prior autoimmune disease
- Uncontrolled metastatic disease of the central nervous system
- Radiotherapy within the 2 weeks before Cycle 1' Day -14
- Surgery within the 2 weeks before Cycle 1' Day -14
- Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications
Sites / Locations
- University of New Mexico Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Hydralazine and Valproic Acid
Arm Description
Starting dose of Hydralazine is 25 mg orally daily, days 1-28. (See Intervention for Dose Escalation Schema) Valproic acid 250 mg orally three times per day for days -14 through -8, then 500 mg orally three times per day daily for days -7 through 28, with the dose titrated to keep the serum level between 0.4 and 0.7 mM.
Outcomes
Primary Outcome Measures
A primary endpoint will be to determine any potential dose limiting toxicities, & the Maximal Tolerated Dose of hydralazine & valproic acid regimen.
Secondary Outcome Measures
To determine any potential anti-tumor effects, as determined by the objective tumor response, clinical benefit, the time to tumor response, the time to tumor progression, and the overall survival.
Full Information
NCT ID
NCT00996060
First Posted
March 26, 2009
Last Updated
January 15, 2016
Sponsor
New Mexico Cancer Care Alliance
1. Study Identification
Unique Protocol Identification Number
NCT00996060
Brief Title
Use of Hydralazine and Valproic Acid in Advanced Solid Tumor Malignancies
Official Title
A Phase 1 Protocol of Hydralazine and Valproic Acid in Advanced Solid Tumor Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
January 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
New Mexico Cancer Care Alliance
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Primary Objective:
The primary endpoint to this study will be to document the toxicities, and reversibility of toxicities, of this regimen of hydralazine and valproic acid in patients with advanced, unresectable, previously treated lung cancers, for whom no acceptable standard therapy is available. A primary endpoint will be to determine any potential dose limiting toxicities, and the Maximal Tolerated Dose of this regimen.
Secondary Objectives:
The secondary endpoint of this study will be to determine any potential anti-tumor effects, as determined by the objective tumor response (complete and partial responses), clinical benefit (complete and partial responses, and clinical benefit), the time to tumor response, the time to tumor progression, and the overall survival.
Detailed Description
This study will be an open-label, non-randomized, dose-escalation phase I trial which will enroll in sequential cohorts.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
Lung Cancer, Advanced Lung Cancer, Unresectable Lung cancer, Previously treated lung cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Hydralazine and Valproic Acid
Arm Type
Experimental
Arm Description
Starting dose of Hydralazine is 25 mg orally daily, days 1-28. (See Intervention for Dose Escalation Schema) Valproic acid 250 mg orally three times per day for days -14 through -8, then 500 mg orally three times per day daily for days -7 through 28, with the dose titrated to keep the serum level between 0.4 and 0.7 mM.
Intervention Type
Drug
Intervention Name(s)
Hydralazine and Valproic Acid: Cohort -1
Other Intervention Name(s)
Depakote (Valproic Acid), Apresoline (Hydralazine)
Intervention Description
Initially, 3 patients will be enrolled into each cohort, beginning with the hydralazine 25 mg PO daily, with the valproic acid dosing beginning two weeks earlier to achieve a steady state level of valproic acid in the blood.
In this cohort, Hydralazine is administered at 10 mg/day.
Intervention Type
Drug
Intervention Name(s)
Hydralazine and Valproic Acid: Cohort 0
Other Intervention Name(s)
Depakote (Valproic Acid), Apresoline (Hydralazine)
Intervention Description
Initially, 3 patients will be enrolled into each cohort, beginning with the hydralazine 25 mg PO daily, with the valproic acid dosing beginning two weeks earlier to achieve a steady state level of valproic acid in the blood.
Hydralazine is administered at 25 mg/day in this cohort.
Intervention Type
Drug
Intervention Name(s)
Hydralazine and Valproic Acid: Cohort 1
Other Intervention Name(s)
Depakote (Valproic Acid), Apresoline (Hydralazine)
Intervention Description
Initially, 3 patients will be enrolled into each cohort, beginning with the hydralazine 25 mg PO daily, with the valproic acid dosing beginning two weeks earlier to achieve a steady state level of valproic acid in the blood.
Hydralazine is administered at 50 mg/day in this cohort.
Intervention Type
Drug
Intervention Name(s)
Hydralazine and Valproic Acid: Cohort 2
Other Intervention Name(s)
Depakote (Valproic Acid), Apresoline (Hydralazine)
Intervention Description
Initially, 3 patients will be enrolled into each cohort, beginning with the hydralazine 25 mg PO daily, with the valproic acid dosing beginning two weeks earlier to achieve a steady state level of valproic acid in the blood.
Hydralazine is administered at 100 mg/day in this cohort as 25 mg four times per day.
Intervention Type
Drug
Intervention Name(s)
Hydralazine and Valproic Acid: Cohort 3
Other Intervention Name(s)
Depakote (Valproic Acid), Apresoline (Hydralazine)
Intervention Description
Initially, 3 patients will be enrolled into each cohort, beginning with the hydralazine 25 mg PO daily, with the valproic acid dosing beginning two weeks earlier to achieve a steady state level of valproic acid in the blood.
Hydralazine is administered at 200 mg/day in this cohort as 50 mg four times per day.
Intervention Type
Drug
Intervention Name(s)
Hydralazine and Valproic Acid: Cohort 4
Other Intervention Name(s)
Apresoline (Hydralazine), Depakote (Valproic Acid)
Intervention Description
Initially, 3 patients will be enrolled into each cohort, beginning with the hydralazine 25 mg PO daily, with the valproic acid dosing beginning two weeks earlier to achieve a steady state level of valproic acid in the blood.
Hydralazine is administered at 300 mg/day in this cohort as 75 mg four times per day.
Intervention Type
Drug
Intervention Name(s)
Hydralazine and Valproic Acid: Cohort 5
Other Intervention Name(s)
Apresoline (Hydralazine), Depakote (Valproic Acid)
Intervention Description
Initially, 3 patients will be enrolled into each cohort, beginning with the hydralazine 25 mg PO daily, with the valproic acid dosing beginning two weeks earlier to achieve a steady state level of valproic acid in the blood.
Hydralazine is administered at 400 mg/day in this cohort as 100 mg four times per day.
Primary Outcome Measure Information:
Title
A primary endpoint will be to determine any potential dose limiting toxicities, & the Maximal Tolerated Dose of hydralazine & valproic acid regimen.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
To determine any potential anti-tumor effects, as determined by the objective tumor response, clinical benefit, the time to tumor response, the time to tumor progression, and the overall survival.
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All patients with lung cancer who have disease which has been previously treated and/or for which there is no acceptable standard treatment regimen available, and cannot be treated definitively with either surgery or radiotherapy.
All will be appropriate candidates for treatment, and are not candidates for treatment with protocols of higher priority.
All patients should have an ECOG/Zubrod/SWOG performance status of less than 2 at the time of the initiation of therapy
Adequate end-organ function
No severe comorbid disease
Ability to provide informed consent.
Signed Informed Consent
ECOG/Zubrod/SWOG Performance Status less than 2
Life expectancy greater than 8 weeks
Male or female' age greater than 18 years
Patients of childbearing potential must be using an effective means of contraception.
Histologic diagnosis of lung cancer that is advanced and cannot be treated adequately by radiotherapy or surgery; or metastatic disease, and for which there is no standard chemotherapeutic option remaining or available
All participants must have either previously received or refused standard chemotherapy
Baseline laboratory values (bone marrow, renal, hepatic):
Adequate bone marrow function:
Absolute neutrophil count greater than 1000/µL
Platelet count greater than 100'000/µL
Renal function:
a. Serum creatinine less than 2.0 mg %
Hepatic function:
Bilirubin less than 1.5x normal
Serum calcium less than 12 mg/dl
Exclusion Criteria
Pregnant or lactating females
Myocardial infarction or ischemia within the 6 months before Cycle 0' Day 0
Uncontrolled' clinically significant dysrhythmia
Prior radiotherapy to an indicator lesion unless there is objective evidence of tumor growth in that lesion
Prior autoimmune disease
Uncontrolled metastatic disease of the central nervous system
Radiotherapy within the 2 weeks before Cycle 1' Day -14
Surgery within the 2 weeks before Cycle 1' Day -14
Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Monte Shaheen, M.D.
Organizational Affiliation
University of New Mexico Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of New Mexico Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.cancer.unm.edu
Description
University of New Mexico Cancer Center
URL
http://www.nmcca.org
Description
New Mexico Cancer Care Alliance
Learn more about this trial
Use of Hydralazine and Valproic Acid in Advanced Solid Tumor Malignancies
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