GTN Therapy on Biomarkers of Immune Escape in Men With Biochemical Recurrence of Prostate Cancer After Primary Therapy

NCT01704274 | Completed Phase 2

• 1 other identifier: Protocol # CAUR 09
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Prostate cancer is the most commonly diagnosed cancer in men in Canada. Over 30% of men over the age of fifty have histological evidence of prostate cancer on biopsy. Despite the stage migration afforded by early detection with serum prostate specific antigen (PSA) testing and an apparent trend toward improved survival over the past several years, prostate cancer remains a significant cause of morbidity and mortality. Biochemical failure after primary therapy (surgery or radiation) remains a significant health care burden and strategies to delay clinical prostate cancer progression and prolong the interval from treatment failure to systemic therapy would be of significant clinical benefit for those men suffering from a finding of PSA recurrence. PSA is widely accepted as the most useful prognostic marker of prostate cancer progression, particularly after primary therapy with radical surgery or radiation. 5 Despite improved cancer control rates with definitive management of early stage prostate cancer, a PSA recurrence is unfortunately a common occurrence (25-50%) in most large case series. Microenvironmental factors have been demonstrated to play a pivotal role in the selection of neoplastic cell subpopulations expressing more malignant phenotypes and contributing to the progression of localized and metastatic disease. Very low levels of O2 (\< 10 mmHg) has been well described in many solid tumours (including prostate cancer) and the extent of hypoxia has been demonstrated to represent an independent marker of a poor prognosis for patients with various types of cancers. Tumour hypoxia contributes to numerous adaptive phenotypes including increased invasion and metastasis, as well as evasion of immune cell surveillance increased resistance to radiotherapy and chemotherapy. Although cellular adaptive responses to hypoxia are likely mediated by various mechanisms, our previous preclinical studies suggest that decreased nitric oxide (NO)-dependent signalling plays a significant role in this progression of a malignant phenotype.

Conditions

Prostate Cancer

Keywords

biochemical; recurrence; prostate; cancer; active; surveillence

Outcome Measures

Primary Outcomes (1)

• Change in the following biomarkers: inflammatory/immune markers uPAR, PAI-1, ULBP2, B7-H1, MIF, TGF-β; and PSA compared to placebo.

  All assessments are as per standard of care. The only additional intervention is a 5 mL peripheral vein phlebotomy at each visit. Patients will be followed at 3, 6, 9 and 12 months after initiation of the trial. Clinic visits will assess side effects of drug and include routine follow-up for prostate cancer management. Serum samples for the above-described makers of immune activity will be obtained at the month 3, 6, 9 and 12 visit.

  12 months

Secondary Outcomes (1)

• Safety and tolerability of SR low-dose GTN patches in the proposed patient population.

  12 months

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo patch

Other: Placebo

Low dose GTN 0.0285 mg/hr

EXPERIMENTAL

Low dose GTN

Other: Low Dose GTN 0.0285 mg/hr

High Dose GTN 0.057 mg/hr

EXPERIMENTAL

High Dose GTN

Other: High Dose GTN 0.057 mg/hr

Interventions

Low Dose GTN 0.0285 mg/hr OTHER

Low Dose GTN

Low dose GTN 0.0285 mg/hr

High Dose GTN 0.057 mg/hr OTHER

High Dose GTN

High Dose GTN 0.057 mg/hr

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males;
• Legal age of consent (18 years of age);
• Histological evidence of adenocarcinoma of the prostate;
• Patients have chosen watchful waiting or active surveillance as preferred management;
• Patients have biochemical failure (defined below) after primary cancer treatment and prefer deferred cancer management:
• Patients with an increasing PSA at least 3 months after surgery (at least two values above PSA 0.2 ng/mL);
• Patients with a PSA 2 ng/ml above their nadir PSA after radiation therapy.

You may not qualify if:

• Inability to provide an informed consent;
• Inability to adhere to the study protocol for any reason;
• Receiving any other adjuvant therapies for prostate cancer less than 6 months prior to study entry;
• Any contraindication to GTN (including concomitant use of nitroglycerin formulations or phosphodiesterase inhibitors).

Sponsors & Collaborators

• Dr. D. Robert Siemens: lead

Study Sites (1)

Centre for Applied Urological Research/Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Recurrence; Neoplasms; Motor Activity

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Study Officials

• D. Robert Siemens, MD FRCSC

  Queen's University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PI

Model Details: One arm placebo, two arms different GTN dose.

Study Record Dates

• First Submitted: October 5, 2012
• First Posted: October 11, 2012
• Study Start: April 1, 2012
• Primary Completion: January 1, 2017
• Study Completion: December 1, 2019
• Last Updated: January 11, 2024

Record last verified: 2024-01

Locations

CA (1)