Nordihydroguaiaretic Acid in Treating Patients With Nonmetastatic Relapsed Prostate Cancer

A Phase I Study of NDGA in Patients With Non-Metastatic Biochemically Relapsed Prostate Cancer

RATIONALE: Nordihydroguaiaretic acid may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of nordihydroguaiaretic acid in treating patients with nonmetastatic relapsed prostate cancer.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: masoprocol

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of nordihydroguaiaretic acid (NDGA) in patients with nonmetastatic, biochemically relapsed prostate cancer.

Secondary

• Determine prostate-specific antigen-modulating effects of NDGA in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oral nordihydroguaiaretic acid (NDGA) twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of NDGA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • UCSF Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate cancer, meeting 1 of the following criteria:

  • Androgen-dependent disease (testosterone ≥ 250 ng/mL)
  • Androgen-independent disease (testosterone < 50 ng/mL)

• Received prior definitive therapy for primary prostate cancer comprising any of the following:

  • External-beam radiotherapy with or without hormonal therapy
  • Brachytherapy with or without pelvic external-beam radiotherapy or hormonal therapy
  • Radical prostatectomy with or without adjuvant or salvage radiotherapy
  • Cryotherapy

• Must have evidence of disease progression, as evidenced by elevated prostate-specific antigen (PSA) that has risen serially from post-definitive therapy nadir on 2 determinations taken ≥ 1 week apart

  • Elevated PSA, meeting 1 of the following criteria:

    • At least 1.0 ng/mL post radiotherapy or cryotherapy
    • At least 4 ng/mL post radical prostatectomy
  • Must show disease progression after discontinuation of the antiandrogen (for patients with androgen-dependent disease receiving antiandrogen as part of primary androgen ablation)
• No metastatic disease, confirmed by negative bone scan and negative CT scan or MRI of abdomen/pelvis

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• Absolute neutrophil count ≥ 1,500/mm³
• Hemoglobin ≥ 8.0 g/dL
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• AST ≤ 1.5 times ULN
• No other medical condition that would interfere with study therapy or compliance
• No other active malignancy except previously treated squamous cell or basal cell skin cancer or cancer that has been treated and considered to be at < 30% risk of relapse
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 8 weeks since prior strontium-chloride Sr 89
• More than 4 weeks since first dose of bisphosphonates
• More than 4 weeks since prior major surgery or radiotherapy

• At least 4 weeks since prior hormonal agents, including megestrol or steroids

  • Concurrent luteinizing hormone-releasing hormone analogs allowed to maintain castrate levels of testosterone
• At least 4 weeks since prior and no concurrent saw palmetto, finasteride, or any herbal agent intended to lower PSA

• Prior adjuvant or neoadjuvant androgen-deprivation therapy allowed for androgen-dependent prostate cancer provided that all of the following are met:

  • No more than 8 months of androgen deprivation
  • At least 12 months since last day of effective androgen deprivation
  • Testosterone > 250 ng/mL at enrollment
• Prior hormonal therapy, chemotherapy, or investigational therapy for biochemical relapse allowed
• No concurrent chemotherapeutic, immunotherapeutic, or other investigational agents
• No concurrent radiotherapy
• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Dose-limiting toxicity as measured by CTC v3.0

Secondary Outcome Measures

Outcome Measure
Maximum tolerated dose
Prostate-specific antigen (PSA) at baseline and on day 1 of each course

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Charles Ryan, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): October 1, 2006
• Study Completion (Actual): October 1, 2006

Study Registration Dates

• First Submitted: April 11, 2006
• First Submitted That Met QC Criteria: April 11, 2006
• First Posted (Estimate): April 12, 2006

Study Record Updates

• Last Update Posted (Estimate): October 11, 2012
• Last Update Submitted That Met QC Criteria: October 9, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: stage III prostate cancer; recurrent prostate cancer; stage I prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Protective Agents; Antioxidants; Lipoxygenase Inhibitors; Masoprocol
• Other Study ID Numbers: CDR0000455645; UCSF-035510; UCSF-H45860-23712-02A