Stereotactic Body Radiation Therapy for Low and Intermediate Risk Prostate Cancer

Adenocarcinoma of the Prostate Clinical Trial

Official title:

Phase I and II Study of Stereotactic Body Radiation Therapy (SBRT) for Low and Intermediate Risk Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03554369
• Other study ID #: STU 072010-019
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 11, 2006
• Est. completion date: December 20, 2021

Study information

• Verified date: May 2019
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There are two separate phases of this study. The purpose of the phase-I is to initially find a potent but reasonably safe dose of a stereotactic body radiation therapy (SBRT) for treating prostate cancer. Once this potent but reasonably safe dose is found, the phase-II will treat additional patients with SBRT to see what effects (good and bad) it has on prostate cancer.

Phase-I

• Primary objective: To escalate the dose of stereotactic radiotherapy to a tumorcidal dose without exceeding the maximum tolerated dose in patients with organ confined prostate cancer.

• Secondary objective: To determine the dose limiting toxicity (DLT) (if the maximum tolerated dose is reached)

Phase-II

• Primary objective: To determine the late severe grade 3-5 Gu and Gi toxicity at nine months from the start of the protocol treatment (graded base on the CTCae v3.0)

• Secondary objective: To determine the 2 year biochemical Prostate Specific Antigen (PSA) control (freedom from PSA failure), disease free and overall survival, local control, freedom from distant metastases, and the incidence of high grade adverse events of any type from the therapy in the treated patients in order to determine if the therapy is promising enough for further clinical investigation.

Description:

A new therapy called stereotactic body radiation therapy (SBRT) for treating prostate cancer which provides fewer treatments but higher doses of radiation per treatment. This is a radiation therapy technique that uses special equipment to position the patient and precisely deliver a large radiation dose to a tumor and not to normal tissue. This research is being done because although SBRT is used to treat a variety of cancers, it hasn't been used extensively to treat prostate cancer and needs more investigation. Stereotactic body radiation therapy (SBRT) for low- to intermediate-risk prostate cancer involves several weeks of treatment sessions.

Blood samples will also be collected before, during, and after treatment as part of this trial. These samples will be collected in patients who chose to participate within 1 week prior to therapy, immediately after first treatment, immediately before second treatment, immediately after fifth treatment, and 6 months after fifth treatment. a doctor, nurse, or licensed technician will collect 50 teaspoons of blood by vein total over the course of the study. investigators may ask for a second blood sample if the research laboratory cannot process the first sample.

Primary End Point:

Phase-I: The primary endpoint of the phase I portion is to either reach the maximum tolerated dose (MTD) or a dose of 50 Gy total (whichever comes first) by escalating the dose of SBRT toward the tumorcidal dose of 50 Gy total. Patients will be treated in cohorts of seven to fifteen.

The phase I portion of the study will be completed when either of the following events occur:

1. The MTD for a cohort is reached or

2. When the highest protocol dose level is treated and tolerated (10 Gy per fraction, total 50 Gy) where we consider the therapy likely to be tumorcidal per determination of the investigators.

Phase-I Dose Escalation: The phase I study is designed to end if the rate of dose limiting toxicity (DLTs) within 90 days from the start of treatment is 33% or higher. For each dose level cohorts, a total of seven to fifteen patients will be enrolled. If zero out of the first seven with 90 day follow-up, two or fewer out of the first nine with 90 day follow-up, three or fewer out of the first twelve with 90 day follow-up, or four or fewer out of the first fifteen of patients with 90 day follow up experience a DLT as defined above, then the dose will escalate to the next dose level. If three or more of the first nine patients, four or more of the first twelve, or five or more of the first fifteen patients experience a DLT, then the MTD will be considered to have been exceeded. The MTD will be defined as the immediately previous lower dose level tolerated. The probability that at least two of nine patients will experience a DLT when the true rate of acute DLTs is 33% is 0.80; that is, the probability of making the correct decision if the true DLT rate is at least 33% is 0.80.

Phase I Waiting Periods:

Dose escalation on the phase I portion of this study should not occur until a sufficient waiting period has occurred after patients have been treated. A period of 90 days must pass in order to assess toxicity. If 90 days have transpired without DLT in each of the first seven (7) patients enrolled to a specific dose level, then dose escalation to the next level may proceed. Patients will continue to be enrolled to each dose level (up to a maximum of 15 patients) with ongoing assessment of those reaching 90 day follow-up so long as either criteria for defining the MTD or criteria for further dose escalation is not reached. If fifteen patients are enrolled to a given dose level yet criteria for adequate follow-up are not reached in a representative sample of patients, further enrollment to the protocol will be suspended until adequate follow-up is reached.

Phase-II: Patients will be treated at either the MTD or highest dose from the phase I study.

Primary Endpoint:

Late severe Genitourinary (GU) and Gastrointestinal (GI) toxicity is defined as grade 3-5 GU and GI toxicity occurring between 270-540 days (i.e., 9-18 months) from the start of the protocol treatment. It is graded based on Common Terminology Criteria for Adverse Events (CTCAE v3.0). Grade 3-5 GU or GI toxicity that originally occurred prior to 270 days from start of protocol treatment will only be considered late severe GU or GI toxicity if it persists at a severity grade of 3-5 based on CTCAE v3.0 after 270 days.

Secondary Endpoints:

• Acute severe GU and GI toxicity is defined as grade 3-5 toxicity occurring prior to 270 days from the start of protocol treatment. It is graded based on CTCAE v3.0.

• Non GU and GI toxicity.

• Biochemical failure Radiation Therapy Oncology Group (RTOG)-American Society for Therapeutic Radiology and Oncology (ASTRO) definition (also known as Phoenix definition)
• Thus, when the PSA rises by more than 2 ng/ml above the lowest level (nadir) achieved after treatment,, biochemical failure has occurred and the date of the failure is recorded at the time the nadir plus 2 ng/ml level is reached.

• Overall survival

• Disease-specific survival

• Clinical progression including local/regional and distant relapse

Sample Size:

1. The sample size of the phase I component of this study will not exceed 45 patients.

2. The sample size of the phase II component of this study will not exceed 50 patients.

Sample Size Estimation: The phase II component of this study is designed to test whether late GU/GI toxicity at 270-540 days from the start of treatment following the protocol treatment is above 10%. The sample size is determined so that the probability of rejecting the treatment because of excessive late toxicity is 90% if the true late toxicity rate is 23% or higher. Assuming an exponential distribution for time from the end of the acute period (270 days from the start of protocol treatment) to the occurrence of late toxicity, the hazard rate for the expected 10% toxicity rate and the unacceptable 23% toxicity rate is 0.006/month and 0.015/month, respectively. Following the asymptotic property of the observed hazard and using Z-test for the logarithm of the hazard ratio, we require 12 cases with severe late GU/GI toxicity. Thus, 47 patients are required to be accrued within three to four years and be followed for 270 days after the acute period (i.e., a total of 540 days) to have a statistical power of 90% with a one-sided significance level of 0.05. Considering 5% ineligible cases and lack-of-data cases, the sample size of the phase II component of this study is 50 patients. Patients treated in phase I at the dose level ultimately used in phase II will be included in the phase II analysis as part of the 50 patient trial.

Study Analysis: This analysis will be carried out when each patient has had at least 270 days (i.e., 9 months) of follow-up after the end of the acute period, a total of 540 days (i.e., 18 months) of follow-up. The hazard rate will be estimated by the life table approach with a time span of 18 months. The one-sided Z-test will be used to test the significance of the difference between the logarithm of the observed hazard rate and the logarithm of the hypothesized hazard rate of 0.006/month with variance equal to the reciprocal of the number of cases with late toxicity observed. Because of the lead time of 9 months for the acute period, the 18-month late toxicity will be estimated by the 9- month toxicity rate using the cumulative incidence approach to the defined time to severe late GU/GI toxicity.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: December 20, 2021
• Est. primary completion date: December 20, 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 120 Years

Eligibility

Inclusion Criteria:

• Patients (Male) who satisfy all of the following conditions will be eligible for this study:

• All patients must be willing and capable to provide informed consent to participate in the protocol

• Eligible patients must have appropriate staging studies identifying them as American Joint Committee on Cancer (AJCC) stage T1 (a, b, or c) or T2 (a and b only) adenocarcinoma of the prostate gland. The patient should not have direct evidence of regional or distant metastases after appropriate staging studies. Histologic confirmation of cancer will be required by biopsy

• The patient's Zubrod performance status must be 0-2

• The Gleason score should be less than or equal to 7

• The serum PSA should be less than or equal to 20 ng/ml prior to starting hormonal therapy (if given) for patients with Gleason score 2-6. For patients with Gleason score of 7, PSA should be less than or equal to 15 ng/ml prior to starting hormonal therapy (if given). As such, the risk of pelvic lymph node involvement according to the Roach formula would be under 20%

• Patients may have used prior hormonal therapy, but it should be limited to no more than 9 months or therapy prior to enrollment

• Patients should not have significant urinary obstructive symptoms; American Urological Association (AUA) score must be = 15 (alpha blockers allowed)

• The ultrasound or CT based volume estimation of the patient's prostate gland should not be greater than 60 grams

• Male of reproductive potential may not participate unless they agreed that they or their partner use an effective contraceptive method such as condom/diaphragm and spermacidal foam, intrauterine device (IUD), or prescription birth control pills

Exclusion Criteria:

• Patients (Female) are not eligible for this study. Patients (Male) with one or more of the following conditions also are ineligible for this study:

• Positive lymph nodes or metastatic disease from prostate cancer

• Prior invasive malignancy unless disease free for a minimum of 3 years (carcinoma in situ of the breast, oral cavity, or cervix, or non-melanomatous skin cancer are all permissible)

• T2c, T3, or T4 tumors

• Previous pelvic radiotherapy

• Previous surgery or chemotherapy for prostate cancer

• Previous transuretheral resection of the prostate (TURP) or cryotherapy to the prostate

• Previous hormonal therapy given for more than 9 months prior to therapy

• Concomitant antineoplastic therapy (including surgery, cryotherapy, conventionally fractionated radiotherapy, and chemotherapy) while on this protocol

• History of Crohn's Disease or Ulcerative Colitis

• Previous significant obstructive symptoms; American Urological Association (AUA) score must be = 15 (alpha blockers allowed)

• Significant psychiatric illness

• Men of reproductive potential may not participate unless they agree to use an effective contraceptive method

• Ultrasound or CT estimate of prostate volume > 60 grams

• Severe, active co-morbidity as defined in the following:

• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months

• Transmural myocardial infarction within the last 6 months

• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration

• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol

• Acquired Immune Deficiency Syndrome (AIDS) based upon current Center for Disease Control and Prevention (CDC) definition; note, however, that Human Immunodeficiency Virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immuno-suppressive. Protocol-specific requirements may also exclude immuno-compromised patients

• History of treatment with potent immuno-suppressive drugs for such conditions as post organ transplant, severe rheumatoid arthritis, etc. within the past 6 months

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Prostate
• Prostatic Neoplasms

Intervention

Radiation:
• Prostate SBRT
Patients will receive 45Gy in 5 fractions of radiation. A minimum of 36 hours and a maximum of 8 days should separate each treatment. No more than 3 fractions will be delivered per week (7 consecutive days). Total dose will depend on the phase of the study

Locations

Country	Name	City	State
United States	UT Southwestern Cancer Center	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity (DLT)	Severity or Toxicity will be graded using the NCI Common Toxicity Criteria for Adverse Events (CTCAE) v. 3.0. A dose- limiting toxicity (DLT) is any treatmentrelated grade 3, 4, or 5 toxicity in the following categories gastrointestinal, renal, genito-urinary, sexual- reproductive, or neurological constitutional symptoms. CTCAE V3.0 along with grades 1-5 is provided in the link for reference (https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pdf).	1-2 Years
Secondary	Acute & Delayed Genitourinary (GU) and Gastrointestinal (GI) toxicity	Severity or Toxicity will be assessed according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 3.0. Dose adjustments should be made according to the system showing the greatest degree of toxicity. The consequences of gastointestinal/renal/genitourinary/sexual and reproductive toxicity should all be graded 1-5 according to the Common Terminology Criteria For Adverse Events (CTCAE), version 3.0 occurring prior to 270 days from the start of protocol treatment. Other treatment related toxicity attributed to the therapy will be captured, recorded and the consequences of should all be graded 1-5 according to the Common Terminology Criteria For Adverse Events (CTCAE). CTCAE V3.0 along with grades 1-5 is provided in the link for reference (https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pdf).	10 Years
Secondary	Biochemical failure RTOG-ASTRO definition (also known as Phoenix definition)	Increase in PSA greater than 2ng/ml above the patients lowest PSA level (nadir) after treatment.	10 Years