Use of Hydralazine and Valproic Acid in Advanced Solid Tumor Malignancies

New Mexico Cancer Care Alliance

Status and phase: Completed; Phase 1

Conditions: Lung Cancer

Treatments: Drug: Hydralazine and Valproic Acid: Cohort 4; Drug: Hydralazine and Valproic Acid: Cohort 0; Drug: Hydralazine and Valproic Acid: Cohort 5; Drug: Hydralazine and Valproic Acid: Cohort 2; Drug: Hydralazine and Valproic Acid: Cohort 1; Drug: Hydralazine and Valproic Acid: Cohort 3; Drug: Hydralazine and Valproic Acid: Cohort -1

Study type: Interventional

Funder types: Other

Identifiers

NCT00996060

NCI-2011-02651 (Registry Identifier)

INST 0712C

Details and patient eligibility

About

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.

Full description

This study will be an open-label, non-randomized, dose-escalation phase I trial which will enroll in sequential cohorts.

Enrollment: 29 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

Hydralazine and Valproic Acid

Experimental group

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.

Treatment:

Drug: Hydralazine and Valproic Acid: Cohort -1

Drug: Hydralazine and Valproic Acid: Cohort 3

Drug: Hydralazine and Valproic Acid: Cohort 1

Drug: Hydralazine and Valproic Acid: Cohort 2

Drug: Hydralazine and Valproic Acid: Cohort 5

Drug: Hydralazine and Valproic Acid: Cohort 0

Drug: Hydralazine and Valproic Acid: Cohort 4