A Pilot Study of Ultra-High-Dose Hypofractionated or Single-Dose Radiotherapy for Intermediate Risk Prostate Cancer (PROSINT)

• ClinicalTrials.gov Identifier: NCT04147806
• Recruitment Status: Recruiting
• First Posted: November 1, 2019
• Last Update Posted: August 25, 2021
• Sponsor: Albert Einstein College of Medicine
• Information provided by (Responsible Party): Albert Einstein College of Medicine

Study Description

Brief Summary:

The present study evaluates clinical outcomes and treatment-related toxicity following definitive ultra-high dose external beam radiotherapy delivered with two different regimens in patients with intermediate-risk adenocarcinoma of the prostate. Modern computer-driven technology enables the implementation of ultra-high hypofractionated Image-Guided Radiotherapy (IGRT) safely.

Prostate cancer patients classified according to the current National Comprehensive Cancer Network (NCCN) guidelines as intermediate risk (biopsy Gleason score of 7 and/or Prostate Specific Antigen (PSA) level >10 and ≤20 ng/mL and/or Stage T1, T2a, T2b or T2c) are eligible for this study.

Patients will undergo IGRT with volumetric intensity-modulated arc radiotherapy (VMAT) with state-of-the-art treatment-planning and quality assurance procedures. Emphasis is placed on normal tissue sparing and delivery accuracy via the use of devices that ensure stability and beam location reproducibility. A rectal balloon with air filling will be used for prostate target immobilization and anatomical reproducibility, while a urethral catheter loaded with beacon transponders will be used to ensure set-up reproducibility and online target tracking. Previously untreated patients with intermediate-risk prostate cancer will be prospectively randomized to receive either 45 Gy in five fractions of 9 Gy each vs. 24 Gy in a single-dose.

Patients will be followed at one month post-treatment and every 3 months for up to 12 months (+/- 4 weeks) and every 6 months thereafter. Acute and chronic toxicity evaluations will focus on urinary, rectal and sexual functions and will be assessed through validated questionnaires. Serum PSA values will be regularly acquired during follow-up. A multiparametric MRI will be performed at baseline, 6, 12 and 24 months following intervention. Additionally, a post-treatment diffusion-weighted MRI (DW-MRI) will be performed within 15 minutes of the first treatment, to measure early physiologic changes, such as perfusion and ischemia, that may correlate with clinically relevant end-points. Post-treatment prostate needle biopsies will be obtained at 24 months to evaluate pathologic response to therapy. The study will be continuously monitored for a minimum of 5 years. In the event unexpected severe (grade ≥3) toxicities are observed in any one of the treatment arms, the study will be terminated according to the stopping rule >3/first 15 patients.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Radiation: IGRT 45 Gy in 5 fractions of 9 Gy; Radiation: IGRT 24 Gy single dose; Drug: Dexamethasone; Drug: Tamsulosin	Phase 2

Detailed Description:

This is open label feasibility study where patients enrolled in the study will undergo image-guided, intensity-modulated radiotherapy using the same equipment, techniques, and treatment-planning procedures as currently practiced at CCU. Eligible patients will receive either 45 Gy in 5 sessions each of 9 Gy delivered in one week (arm A) or 24 Gy in 1 session (arm B) to assess the dose limiting toxicities in the two groups. Patients will be randomized to arm A or arm B.

Dose limiting toxicity (DLT) is defined as any Grade 3 urinary or rectal toxicity, based on NCI CTCAE v4.0, observed within 3 months of completion of protocol radiation. If, at any point in the conduct of the trial, DLTs are observed in three patients in a study arm, accrual to that arm will be terminated.

There are three aspects of this study that will be different from the currently used standard treatment for definitive external beam treatment of prostate cancer:

1. The dose-fractionation scheme, as per the treatment arm.
2. Acquisition of a set of prostate biopsies at 24 months post treatment
3. Examination of imaging response based on multi-parametric MRI

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Ultra-High-Dose Hypofractionated or Single-Dose Radiotherapy for Intermediate Risk Prostate Cancer
• Actual Study Start Date: August 1, 2016
• Estimated Primary Completion Date: May 25, 2022
• Estimated Study Completion Date: August 1, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: IGRT 45 Gy in 5 fractions of 9 Gy; Hypofractionated IGRT at a prescription dose of 45 Gy in 5 fractions of 9 Gy delivered in five consecutive days	Radiation: IGRT 45 Gy in 5 fractions of 9 Gy; Administration of 9 Gy in five consecutive days, to a total dose of 45 Gy radiation; Radiation: IGRT 24 Gy single dose; Administration of a single dose of 24 Gy in one session; Drug: Dexamethasone; 4 mg by mouth on treatment days only; Other Name: Dexasone; Drug: Tamsulosin; 0.4 mg by mouth daily starting the day of simulation and until 2 weeks post-treatment.; Other Name: Flomax Relief
Experimental: IGRT 24 Gy single dose; single fraction IGRT at a prescription dose of 24 Gy	Radiation: IGRT 45 Gy in 5 fractions of 9 Gy; Administration of 9 Gy in five consecutive days, to a total dose of 45 Gy radiation; Radiation: IGRT 24 Gy single dose; Administration of a single dose of 24 Gy in one session; Drug: Dexamethasone; 4 mg by mouth on treatment days only; Other Name: Dexasone; Drug: Tamsulosin; 0.4 mg by mouth daily starting the day of simulation and until 2 weeks post-treatment.; Other Name: Flomax Relief

Outcome Measures

Primary Outcome Measures :

1. Number of patients with treatment-related adverse events as assessed by Common Toxicity Criteria for Adverse Effects v4.0 [ Time Frame: Participants should be followed continuously, for the duration of 5 years ]
   Comparison of treatment related adverse events as measured by Common Toxicity Criteria for Adverse Effects v4.0 over a 5 year time frame

Secondary Outcome Measures :

1. Biochemical outcome based on Prostate Specific Antigen (PSA) assessment [ Time Frame: Participants should be followed continuously for the duration of 5 years ]
   PSA assessment will be done
2. Quality of life assessment based on International Prostate Symptom Score (IPSS) [ Time Frame: Participants should be followed continuously for the duration of 5 years ]
   The International Prostate Symptom Score (IPSS) can be utilized to measure the severity of lower urinary tract symptoms.The IPSS is made up of 7 questions related to voiding symptoms. A score of 0 to 7 indicates mild symptoms, 8 to 19 indicates moderate symptoms and 20 to 35 indicates severe symptoms.
3. Pathological response based on biopsy at 24 months post-treatment [ Time Frame: Participants should be followed continuously for the duration of 5 years ]
   Pathology will be evaluated
4. Quality of life assessment based on International Index of Erectile Function (IIEF) [ Time Frame: Participants should be followed continuously for the duration of 5 years ]
   Quality of life survey

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Signed study specific informed consent form;
• Histologic confirmation of adenocarcinoma of the prostate by biopsy;
• PSA ≤ 20 ng/mL;
• Gleason score 7;
• Staging MRI must confirm American Joint Committee on Cancer (AJCC) stage T1, T2a, T2b or T2c;
• No direct evidence of regional or distant metastases after appropriate staging studies;
• Age ≥ 50;
• Performance Status 0-2;
• Internation Prostate Symptom Score score must be ≤ 15 (alpha blockers allowed);
• CT scan or Ultrasound-based volume estimation of prostate gland ≤ 100 grams;

Exclusion Criteria:

• Positive lymph-nodes or metastatic disease from prostate cancer on imaging studies
• Prior invasive malignancy unless disease-free for a minimum of 5 years
• Tumour Clinical stage T3 or T4 on MRI
• PSA > 20 ng/mL
• Gleason score > 7
• Previous pelvic radiotherapy
• Previous surgery for prostate cancer
• Previous transurethral resection of the prostate (TURP)
• History of Crohn's Disease or Ulcerative Colitis
• Previous significant urinary obstructive symptoms
• Significant psychiatric illness
• Ultrasound or CT estimate of prostate volume > 100 grams
• Severe, active co-morbidity

Contacts and Locations

Contacts

Contact: Sarah Yukelis; 718-920-5636; syukelis@montefiore.org

Contact: Hilda Haynes-Lewis; 718-920-8819; hhaynes@montefiore.org

Locations

United States, New York

Montefiore Medical Center - Moses Campus; Recruiting

Bronx, New York, United States, 10467-2490

Contact: Madhur K. Garg 718-920-4361 aecc@aecom.yu.edu

Principal Investigator: Madhur K. Garg

Sponsors and Collaborators

Albert Einstein College of Medicine

Investigators

• Principal Investigator: Madhur Garg, MD; Associate Clinical Director

More Information

• Responsible Party: Albert Einstein College of Medicine
• ClinicalTrials.gov Identifier: NCT04147806
• Other Study ID Numbers: 2016-6545
• First Posted: November 1, 2019
• Last Update Posted: August 25, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Dexamethasone; Tamsulosin; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents