Intensity Modulated Radiation Therapy for Prostate Cancer

NCT00214422 | Completed Early Phase 1 Results

• 2 other identifiers: 05024105-C-0241
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

BACKGROUND:

• This study represents a progression from findings in four previous National Cancer Institute (NCI) Radiation Oncology Branch (ROB) protocols (02-C-0167A, 02-C-0207E, 03-C-0190B, 04-C-0171). In these previous works we have begun to develop techniques to obtain Magnetic Resonance (MR) biological images and co-register tissue in prostate cancer patients. OBJECTIVES:
• The primary objective of the first portion of this study is to assess the feasibility of using Intensity-modulated radiation therapy (IMRT) to treat the at-risk lymph nodes in prostate cancer. Also, if feasible, we hope optimize this technique with experience. ELIGIBILITY:
• This is a study of image guided, targeted radiation therapy in patients with high risk of nodal metastases from prostate cancer. Patients with prostate cancer who have more than 15% risk of lymph node (as defined by the Partin tables) metastasis will be eligible for this study. DESIGN:
• On the first 10 patients, we will perform approximately 5 computed tomography (CT) simulations throughout the course of their therapy. On each simulation, the initial treatment plan will be re-run. The dose-volume data from target and normal tissues will then be re-analyzed. From this analysis we will be better able to determine the size of margins needed to account for organ motion and changes such as varying amounts of gas in the bowel and fluid in the bladder. To the best of our knowledge, no such analyses have been published.
• If the initial part of this trial is feasible, we will proceed to a phase I dose escalation trial of radiation to the at-risk lymph nodes. The primary statistical objective of the phase I portion of this study is to estimate the Maximum Tolerated Dose (MTD) of external beam radiation based on evaluating acute toxicity. The study will be conducted with a dose-escalation design with 3 patients in each dose cohort. If fewer than 2 of 3 patients experience an acute dose limiting toxicity (DLT) than patients will be accrued to the next dose cohort. If 2 or more of 3 patients experience a DLT then the MTD will be exceeded and the prior, lower dose cohort will be considered the MTD. Secondary objectives of this study are to relate patterns in gene and protein expression to response and toxicity and to evaluate the frequency of late term toxicity.
• Specific procedures and risks will be described in a separate consent to be obtained at the time of biopsy. Tissue samples will be processed for complementary deoxyribonucleic acid (cDNA) microarray testing and stored for future analysis in the Radiation Oncology Branch, NCI.
• Anatomic Magnetic Resonance Imaging (MRI) and magnetic resonance (MR) biological images of the prostate and pelvis will be obtained and tissue will be acquired with biopsy locations precisely translated (co-registered) to an MR image of reference. A fiducial marker (gold seed) will be left at the biopsy site as a fiducial marker to direct future radiation therapy to the prostate. If necessary, additional fiducial markers will be placed for prostate localization during treatment.

Conditions

Prostate Cancer

Keywords

Prostate; Radiation; Cancer; Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Any Grade 2 Toxicity Using Intensity Modulated Radiation Therapy (IMRT) to Treat the At-risk Lymph Nodes in Prostate Cancer ( up to First 10 Patients)

  Radiation side effects were assessed by the Radiation Oncology Group (RTOG) Acute/Late Toxicity Grading Gastrointestinal and Genitourinary criteria. Acute Grade 0 - no symptoms, Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life threatening, and Grade 5 is death directly related to radiation side effects. Late toxicity is defined as occurring after 90 days.

  At one week, one month, 2 months, 3 months, 6 months, 9 months, 1 year, 18 months, 2 years, 30 months, and 3 years after radiation therapy

• Maximum Tolerated Dose (MTD) of External Beam Radiation to Pelvic Lymph Nodes of Interest in Patients Receiving Radiation Therapy for Prostate Cancer (After the First 10 Patients) In Arm 1, Arm 2, and Arm 3

  Maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 or more in a cohort of either 3 or 6 patients experiences a dose limiting toxicity (DLT) attributed to radiation therapy. An acute DLT will be defined as Radiation Therapy Oncology Group (RTOG) grade 3 or greater, acute gastrointestinal or genitourinary toxicity within 3 months after the completion of radiation.

  Completion of Treatment, an average of 8.5 weeks

Secondary Outcomes (4)

• Number of Participants With Grade 2 Late Gastrointestinal or Genitourinary Toxicity Assessed by the Radiation Oncology Group (RTOG) Criteria

  At median follow-up, approximately 28 months following radiation

• Number of Participants With a Dose Limiting Toxicity (DLT)

  Within 3 months after completion of radiation

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 8 years and 3.5 months.

• Number of Participants With Grade 3 or 4 Acute and/or Late Gastrointestinal or Genitourinary Toxicity Assessed by the Radiation Oncology Group (RTOG) Criteria

  At median follow-up, approximately 28 months following radiation

Study Arms (3)

Arm 1- 5040cGy to the lymph nodes

EXPERIMENTAL

5040Gray (cGy) to the lymph nodes

Radiation: Radiation

Arm 2 - 5400cGy to the lymph nodes

EXPERIMENTAL

5400Gray (cGy) to the lymph nodes

Radiation: Radiation

Arm 3 - 5900cGy to the lymph nodes

EXPERIMENTAL

5900Gray (cGy) to the lymph nodes

Radiation: Radiation

Interventions

Radiation RADIATION

Radiation will be given in dose escalations from 5040 Gray (cGy) to a maximum of 5900 cGy to lymph nodes.

Arm 1- 5040cGy to the lymph nodes; Arm 2 - 5400cGy to the lymph nodes; Arm 3 - 5900cGy to the lymph nodes

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Pathology report confirming adenocarcinoma of the prostate
• Risk of lymph node metastasis greater than or equal to15% as defined by the Partin tables or biopsy proven positive lymph nodes
• Tumor visible on magnetic resonance imaging (MRI)
• No prior surgery, radiation, or chemotherapy for prostate cancer, with the exception of hormone therapy which may be given neoadjuvantly for up to four (4) months.
• Age greater than 18 years old and less than 90 years old.

You may not qualify if:

• Cognitively impaired patients who cannot give informed consent.
• Patients with metastatic disease beyond the pelvis
• Contraindication to biopsy
• Bleeding disorder
• Prothrombin time (PT)/partial thromboplastin time (PTT) greater than or equal to 1.5 times the upper limit of normal
• Platelets less than or equal to 50K
• Artificial heart valve
• Contraindication to MRI
• Patients weighing greater than136 kgs (weight limit for the scanner tables)
• Allergy to magnetic resonance (MR) contrast agent
• Patients with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic devices.
• Pre-existing and active prostatitis or proctitis
• Other medical conditions deemed by the principal investigator (PI) or associates to make the patient ineligible for protocol investigations, procedures, and high-dose external beam radiotherapy.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E, von Eschenbach AC, Kuban DA, Rosen I. Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002 Aug 1;53(5):1097-105. doi: 10.1016/s0360-3016(02)02829-8.

  PMID: 12128107 BACKGROUND

• Roach M 3rd, DeSilvio M, Lawton C, Uhl V, Machtay M, Seider MJ, Rotman M, Jones C, Asbell SO, Valicenti RK, Han S, Thomas CR Jr, Shipley WS; Radiation Therapy Oncology Group 9413. Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol. 2003 May 15;21(10):1904-11. doi: 10.1200/JCO.2003.05.004.

  PMID: 12743142 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasms

Interventions

Radiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Phenomena

Results Point of Contact

• Title: Dr. Kevin Camphausen
• Organization: National Cancer Institute

camphausen@nih.gov

240-760-6205

Study Officials

• Kevin A Camphausen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 19, 2006
• First Posted: September 21, 2005
• Study Start: September 19, 2005
• Primary Completion: May 27, 2014
• Study Completion: April 18, 2018
• Last Updated: July 19, 2019
• Results First Posted: March 1, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)