Randomized Trial of Suicide Gene Therapy and Prostate Cancer (ReCAP)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Benjamin Movsas, M.D., Henry Ford Health System
ClinicalTrials.gov Identifier:
NCT00583492
First received: December 20, 2007
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

This is a randomized, controlled trial that will test the hypothesis that replication-competent adenovirus-mediated suicide gene therapy in combination with 80 Gy intensity modulated radiotherapy (IRMT)will improve freedom from failure (FFF) relative to 80 Gy IMRT alone in patients with newly-diagnosed prostate cancer with an intermediate-risk profile.


Condition Intervention Phase
Prostate Cancer
Biological: Ad5-yCD/mutTKSR39rep-ADP
Radiation: IMRT
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Controlled Trial of Replication-Competent Adenovirus-Mediated Suicide Gene Therapy in Combination With IMRT Versus IMRT Alone for the Treatment of Newly-Diagnosed Prostate Cancer With an Intermediate Risk Profile

Resource links provided by NLM:


Further study details as provided by Henry Ford Health System:

Primary Outcome Measures:
  • Freedom from failure (FFF) (biochemical by PSA level or clinical by biopsy) [ Time Frame: 8 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Acute (<=90 days) and long term (>90 days) GI/GU toxicity [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Prostate biopsy status (12 cores) at 2 years [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Freedom from distant metastases [ Time Frame: 5 + years ] [ Designated as safety issue: No ]
  • Disease-specific and overall survival [ Time Frame: 5 + years ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: December 2007
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gene Therapy + IMRT
Gene Therapy + IMRT
Biological: Ad5-yCD/mutTKSR39rep-ADP
  1. x 10e12 sterile injectable solution, 1 injection on day one Plus Radiation - 40 x 2 Gy for a total dose of 80 Gy or 44 x 1.8 Gy for a total dose of 79.2 Gy Plus
  2. week course (weekdays only) of 5-FC and vGCV prodrug therapy
Active Comparator: IMRT Alone
IMRT: 40 x 2 Gy for a total dose of 80 Gy or 44 x 1.8 Gy for a total dose of 79.2 Gy
Radiation: IMRT
40 x 2 Gy for a total dose of 80 Gy or 44 x 1.8 Gy for a total dose of 79.2 Gy

Detailed Description:

OBJECTIVES

This is a randomized, controlled trial that will test the hypothesis that replication-competent adenovirus-mediated suicide gene therapy in combination with 80 Gy intensity modulated radiotherapy (IRMT)will improve freedom from failure (FFF) relative to 80 Gy IMRT alone in patients with newly-diagnosed prostate cancer with an intermediate-risk profile.

The trial contains two treatment arms:

Arm 1- Gene Therapy + IMRT Arm 2- IMRT

The study will be stratified by clinical site and pre-treatment risk factors (e.g., % positive biopsy cores, Gleason score.

  • Gleason score 5/6 AND PSA <10 ng/mL; AND >=50% positive biopsy cores
  • (Gleason score 5/6 and PSA 10-20 ng/mL) OR (Gleason score 7 and PSA 0 - 20 ng/mL); AND <50% positive biopsy cores
  • Gleason score 5/6 and PSA 10-20 ng/mL) OR (Gleason score 7 and PSA 0-20 ng/mL) AND >=50% positive biopsy cores.

An interim safety analysis (Interim Analysis 1) will be conducted after the first 21 patients in the investigational therapy arm, and a total of 42 subjects in both arms, have completed the 90 day toxicity assessment following randomization (phase 2 component). If, at this point, there are no safety concerns as determined by the Data and Safety Monitoring Board (DSMB), the trial will continue as a phase 3 study with two additional interim analyses (Interim Analyses 2 & 3). The primary analysis for treatment efficacy will be based on all randomized subjects.

Primary

To assess the relative efficacy of replication-competent adenovirus-mediated suicide gene therapy in combination with 80 Gy intensity modulated radiotherapy (IMRT) versus 80 Gy IMRT alone in patients with newly-diagnosed prostate cancer with an intermediate-risk profile. The primary endpoint is freedom from failure (FFF) (biochemical or clinical).

Secondary

To assess the difference between the two treatment arms for:

  • Acute (<= 90 days) and long-term (> 90 days) toxicity.
  • Prostate biopsy status (12 cores) at 2 years.
  • Freedom from distant metastases.
  • Disease-specific and overall survival.
  • Quality of life.

Exploratory

To examine:

  • Possible effect of gene therapy on PSA doubling time (PSADT) after PSA failure.
  • Possible association between the primary and secondary outcomes and Ad5-yCD/mutTKSR39rep-ADP adenovirus persistence (as measured by adenoviral DNA in blood).
  • Possible association between the primary and secondary outcomes and specific immunological endpoints including levels of circulating CD4+ and CD8+ T lymphocytes, T-cell proliferation response, cytotoxic T lymphocyte (CTL) response, and development of antibodies to prostate-specific antigens.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men with histologically-confirmed adenocarcinoma of the prostate within 180 days prior to registration. To be eligible, the subjects must have one of the following conditions:

    • Stage T1 or T2, Gleason Score 7, PSA <= 20 ng/mL, Any number positive biopsy cores
    • Stage T1 or T2, Gleason Score 5 or 6, PSA >=10 ng/mL and <20 ng/mL, Any number positive biopsy cores
    • Stage T1 or T2, Gleason Score 5 or 6, PSA <10 ng/mL and >=50% positive biopsy cores
  • Negative lymph nodes as established by imaging, nodal sampling, or dissection within 90 days prior to registration.
  • No evidence of metastatic disease as evaluated by bone scan and CT scan of the abdomen and pelvis within 90 days prior to registration
  • Karnofsky performance status >=70
  • Subjects must have adequate baseline organ function, as assessed by the following laboratory values, within 30 days before initiating the study
  • Adequate renal function with serum creatinine <=1.5 mg/dL or creatinine clearance >=45 mL/min/m2.
  • Platelet count > 100,000/μL.
  • Absolute neutrophil count > 1,000/μL.
  • Hemoglobin > 10.0 g/dL.
  • Normal partial thromboplastin time (PTT) and prothrombin (PT).
  • Bilirubin < 1.5 mg/dL; SGOT and SGPT < 2.5 times upper limit of normal (ULN).
  • Men of child-producing potential must be willing to consent to use effective contraception while on treatment and for at least 3 months afterwards.
  • Subjects must possess the ability to give informed consent and express a willingness to meet all of the expected requirements of the protocol for the duration of the study.

Exclusion Criteria:

Subjects with the following conditions will be excluded from the study:

  • Stage >= T3.
  • PSA > 20 ng/mL.
  • Gleason score >= 8.
  • Prostate volume >120cc.
  • Pathologically positive lymph nodes or nodes > 1.5 cm on imaging. Note: nodes > 1.5 cm but biopsy negative are allowed.
  • Evidence of M1 metastatic disease.
  • Prior invasive malignancy except for non-melanoma skin cancer within 5 years of enrollment.
  • Prognosis for survival of < 5 years.
  • Prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy for any reason.
  • Prior radiotherapy, including brachytherapy, to the region of the study cancer that would result in overlap of radiation fields.
  • Prior or planned androgen suppression therapy or prior systemic chemotherapy for the study cancer. Note that prior chemotherapy for a different cancer is allowed; however, patients must be >2 years post-completion of chemotherapy at time of registration. Patients on Proscar therapy must stop to be eligible.
  • Severe, active co-morbidity defined as:
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months.
  • Transmural myocardial infarction within the last 6 months.
  • Acute infection. Acute infection is defined by any viral, bacterial, or fungal infection that requires specific therapy within 72 hours of initiation of the study therapy.
  • Positive serological test for HIV at baseline.
  • Previous history of liver disease including hepatitis.
  • Immunosuppressive therapy including systemic corticosteroids. Use of inhaled and topical corticosteroids is permitted.
  • Impaired immunity or susceptibility to serious viral infections.
  • Allergy to any product used in the protocol. (If the subject has an allergy to Ciprofloxacin, another antibiotic can be substituted at the discretion of the treating physician.
  • Serious medical or psychiatric illness or concomitant medication, which, in the judgment of the principal investigator, might interfere with the subject's ability to respond to or tolerate the treatment or complete the trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00583492

Locations
United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21231
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
Sponsors and Collaborators
Henry Ford Health System
Investigators
Principal Investigator: Benjamin Movsas, M.D. Henry Ford Health System
  More Information

Additional Information:
Publications:

Responsible Party: Benjamin Movsas, M.D., Chairman, Department of Radiation Oncology, Henry Ford Health System
ClinicalTrials.gov Identifier: NCT00583492     History of Changes
Other Study ID Numbers: Prostate4809, P01 CA098012
Study First Received: December 20, 2007
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Henry Ford Health System:
Prostatic Neoplasms
Prostate Cancer
Adenocarinomas
Tumors of the Prostate
Gene Therapy
IMRT

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on September 18, 2014