Use of Hydralazine and Valproic Acid in Advanced Solid Tumor Malignancies

NCT ID: NCT00996060

Last Updated: 2016-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2013-01-31

Brief Summary

1. 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.

2. 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.

Conditions

Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Hydralazine and Valproic Acid

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.

Group Type: EXPERIMENTAL

Hydralazine and Valproic Acid: Cohort -1

Intervention Type: DRUG

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.

Hydralazine and Valproic Acid: Cohort 0

Intervention Type: DRUG

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.

Hydralazine and Valproic Acid: Cohort 1

Intervention Type: DRUG

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.

Hydralazine and Valproic Acid: Cohort 2

Intervention Type: DRUG

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.

Hydralazine and Valproic Acid: Cohort 3

Intervention Type: DRUG

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.

Hydralazine and Valproic Acid: Cohort 4

Intervention Type: DRUG

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.

Hydralazine and Valproic Acid: Cohort 5

Intervention Type: DRUG

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.

Interventions

Hydralazine and Valproic Acid: Cohort -1

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

Hydralazine and Valproic Acid: Cohort 0

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

Hydralazine and Valproic Acid: Cohort 1

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

Hydralazine and Valproic Acid: Cohort 2

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

Hydralazine and Valproic Acid: Cohort 3

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

Hydralazine and Valproic Acid: Cohort 4

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

Hydralazine and Valproic Acid: Cohort 5

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.

Intervention Type: DRUG

Other Intervention Names

Depakote (Valproic Acid); Apresoline (Hydralazine); Depakote (Valproic Acid); Apresoline (Hydralazine); Depakote (Valproic Acid); Apresoline (Hydralazine); Depakote (Valproic Acid); Apresoline (Hydralazine); Depakote (Valproic Acid); Apresoline (Hydralazine); Apresoline (Hydralazine); Depakote (Valproic Acid); Apresoline (Hydralazine); Depakote (Valproic Acid)

Eligibility Criteria

Inclusion Criteria

1. 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.

2. All will be appropriate candidates for treatment, and are not candidates for treatment with protocols of higher priority.

3. All patients should have an ECOG/Zubrod/SWOG performance status of less than 2 at the time of the initiation of therapy

4. Adequate end-organ function

5. No severe comorbid disease

6. Ability to provide informed consent.

7. Signed Informed Consent

8. ECOG/Zubrod/SWOG Performance Status less than 2

9. Life expectancy greater than 8 weeks

10. Male or female' age greater than 18 years

11. Patients of childbearing potential must be using an effective means of contraception.

12. 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

13. All participants must have either previously received or refused standard chemotherapy

14. Baseline laboratory values (bone marrow, renal, hepatic):

Adequate bone marrow function:

1. Absolute neutrophil count greater than 1000/µL

2. Platelet count greater than 100'000/µL

Renal function:

a. Serum creatinine less than 2.0 mg %

Hepatic function:

1. Bilirubin less than 1.5x normal

2. Serum calcium less than 12 mg/dl

Exclusion Criteria

1. Pregnant or lactating females

2. Myocardial infarction or ischemia within the 6 months before Cycle 0' Day 0

3. Uncontrolled' clinically significant dysrhythmia

4. Prior radiotherapy to an indicator lesion unless there is objective evidence of tumor growth in that lesion

5. Prior autoimmune disease

6. Uncontrolled metastatic disease of the central nervous system

7. Radiotherapy within the 2 weeks before Cycle 1' Day -14

8. Surgery within the 2 weeks before Cycle 1' Day -14

9. Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New Mexico Cancer Research Alliance

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Monte Shaheen, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of New Mexico Cancer Center

Locations

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Countries

United States

Related Links

http://www.cancer.unm.edu

University of New Mexico Cancer Center

http://www.nmcca.org

New Mexico Cancer Care Alliance

Other Identifiers

NCI-2011-02651

Identifier Type: REGISTRY

Identifier Source: secondary_id

INST 0712C

Identifier Type: -

Identifier Source: org_study_id