Randomized Trial of Suicide Gene Therapy and Prostate Cancer

NCT00583492 | Completed Phase 2 Results DMC

• 1 other identifier: Prostate4809
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

Prostatic Neoplasms; Prostate Cancer; Adenocarinomas; Tumors of the Prostate; Gene Therapy; IMRT

Outcome Measures

Primary Outcomes (1)

• Freedom From Biochemical/Clinical Failure (FFF)

  Biochemical/Clinical Failure was defined as PSA nadir plus 2 ng/mL

  5 years

Secondary Outcomes (5)

• Acute >= Grade 3 Treatment-related Toxicity

  90 days

• Positive Prostate Biopsy at 2 Years

  2 years

• Freedom From Distant Metastases

  10 years

• Disease-specific Survival

  10 years

• Decrease in Quality of Life

  3 years

Study Arms (2)

Ad5-yCD/mutTKSR39rep-ADP + IMRT

EXPERIMENTAL

Gene Therapy + IMRT

Biological: Ad5-yCD/mutTKSR39rep-ADP

IMRT Alone

ACTIVE COMPARATOR

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

Interventions

Ad5-yCD/mutTKSR39rep-ADP BIOLOGICAL

Ad5-yCD/mutTKSR39rep-ADP (1 x 10\^12 vp) on day 1 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

Ad5-yCD/mutTKSR39rep-ADP + IMRT

IMRT 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

IMRT Alone

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Subjects with the following conditions will be excluded from the study:
• Stage \>= T3.
• Prostate specific antigen (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.

Sponsors & Collaborators

• Henry Ford Health System: lead

Study Sites (2)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21231, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Related Publications (5)

• Freytag SO, Khil M, Stricker H, Peabody J, Menon M, DePeralta-Venturina M, Nafziger D, Pegg J, Paielli D, Brown S, Barton K, Lu M, Aguilar-Cordova E, Kim JH. Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. Cancer Res. 2002 Sep 1;62(17):4968-76.

  PMID: 12208748 BACKGROUND

• Freytag SO, Stricker H, Peabody J, Pegg J, Paielli D, Movsas B, Barton KN, Brown SL, Lu M, Kim JH. Five-year follow-up of trial of replication-competent adenovirus-mediated suicide gene therapy for treatment of prostate cancer. Mol Ther. 2007 Mar;15(3):636-42. doi: 10.1038/sj.mt.6300068. Epub 2007 Jan 16.

  PMID: 17228316 BACKGROUND

• Freytag SO, Stricker H, Pegg J, Paielli D, Pradhan DG, Peabody J, DePeralta-Venturina M, Xia X, Brown S, Lu M, Kim JH. Phase I study of replication-competent adenovirus-mediated double-suicide gene therapy in combination with conventional-dose three-dimensional conformal radiation therapy for the treatment of newly diagnosed, intermediate- to high-risk prostate cancer. Cancer Res. 2003 Nov 1;63(21):7497-506.

  PMID: 14612551 BACKGROUND

• Freytag SO, Movsas B, Aref I, Stricker H, Peabody J, Pegg J, Zhang Y, Barton KN, Brown SL, Lu M, Savera A, Kim JH. Phase I trial of replication-competent adenovirus-mediated suicide gene therapy combined with IMRT for prostate cancer. Mol Ther. 2007 May;15(5):1016-23. doi: 10.1038/mt.sj.6300120. Epub 2007 Mar 20.

  PMID: 17375076 BACKGROUND

• Freytag SO, Stricker H, Lu M, Elshaikh M, Aref I, Pradhan D, Levin K, Kim JH, Peabody J, Siddiqui F, Barton K, Pegg J, Zhang Y, Cheng J, Oja-Tebbe N, Bourgeois R, Gupta N, Lane Z, Rodriguez R, DeWeese T, Movsas B. Prospective randomized phase 2 trial of intensity modulated radiation therapy with or without oncolytic adenovirus-mediated cytotoxic gene therapy in intermediate-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2014 Jun 1;89(2):268-76. doi: 10.1016/j.ijrobp.2014.02.034. Epub 2014 May 5.

  PMID: 24837889 RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Benjamin Movsas
• Organization: Henry Ford Health System

bmovsas1@hfhs.org

313-516-2319

Study Officials

• Benjamin Movsas, M.D.

  Henry Ford Health System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chairman, Department of Radiation Oncology

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: December 31, 2007
• Study Start: December 1, 2007
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: March 17, 2016
• Results First Posted: March 17, 2016

Record last verified: 2016-02

Locations

US (2)