Prostate Adenocarcinoma, Prostate Cancer
Conditions
Brief summary
1. The investigators hypothesize that increasing radiation dose to the functional MRI-defined lesion in the prostate bed will result in an improved initial complete response (reduction in prostate-specific antigen (PSA) to \< 0.1 ng/mL), which is related to long-term outcome biochemically. 2. Biomarker expression levels differ in the DCE-MRI enhancing and non-enhancing tumor regions (when applicable). 3. 10-15% of men undergoing RT have free circulating DNA (fcDNA) or tumor cells (CTC) that are related to an adverse treatment outcome. 4. Prostate cancer-related anxiety will be reduced in the MRI targeted SRT arm, because the patients will be aware that the dominant tumor will be targeted with higher radiation dose (compared to those pts who were treated on standard arm prior to its closure).
Detailed description
Phase 3 arms I (SSRT) and II (MTSRT) were closed. Study recruitment was suspended until re-opening as a single-arm Phase 2 (MTSRT) study.
Interventions
RADIATIONStandard Salvage Radiation Treatment (SSRT)
A total dose of 68 Gy delivered in 34 fractions to the Clinical Target Volume (CTV), 51 Gy in 34 fractions can be given to the pelvic nodes.
RADIATIONMapped Tumor Salvage RT (MTSRT)
Dose escalation to the imaging or Dynamic Contrast Enhanced MRI (DCE-MRI)-defined dominant region(s) by dose painting at 2.25 Gy per fraction, while the rest of the Clinical Target Volume (CTV) receives 2.0 Gy a fraction to 68 Gy. The mapped tumor (MT) boost region will receive an absolute dose of 76.5 Gy. Assuming an α/β ratio of 3.0, this would be equivalent to 80 Gy in 2.0 Gy fractions.
Sponsors
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
35 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Prostate cancer patients with a PSA after prostatectomy of at least 0.1 ng/mL and up to 4.0 ng/mL within 3 months prior to enrollment. 2. Patients with or without palpable abnormalities on digital rectal exam (DRE) are eligible. 3. Minimum of 3 months since prostatectomy to allow for return of urinary continence and healing. 4. Imaging detectable lesion or lesions in prostate bed or regional lymph node (LN). Each lesion should be at least 0.4 cc and a maximum of 6 cc and was obtained ≤ 3 months prior to protocol entry or enrollment. 5. No evidence of metastatic (distant) disease (pelvic nodes are allowed up to common iliac). 6. Negative bone scan if deemed necessary by treating physician obtained ≤ 4 months prior to protocol entry or enrollment. 7. No previous pelvic radiotherapy. 8. Serum total testosterone taken within 3 months prior to enrollment. 9. No concurrent, active malignancy, other than nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for ≥ 3 years then the patient is eligible. 10. Ability to understand and the willingness to sign a written informed consent document. 11. Zubrod performance status \< 2. 12. Patients must agree to fill out quality of life/psychosocial questionnaires. 13. Age ≥ 35 and ≤ 85 years.
Exclusion criteria
a. Prior androgen deprivation therapy is not permitted if it was within 6 months previous to signing consent form. (NOTE: Therapy given as part of the planned course of radiation is allowed).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PSA Response Rate | Up to 23 months | Prostate-Specific Antigen (PSA) response rate is defined as the percentage of study patients with PSA less than 0.1 ng/mL at 21 months after completion of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Toxicity | Up to 8 months | Incidence of treatment-emergent toxicity in study participants. Toxicity is defined as adverse events (AEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs)Acute toxicity is defined as toxicity occurring during treatment and within three months of completing treatment. Late toxicity is toxicity occurring more than three months after treatment completion. Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |
| Health-Related Quality of Life Scores: EPIC SF-12 | Up to 65 months | Health-related Quality of Life (HRQOL) will be measured using the Expanded Prostate Cancer Index Composite and Medical Outcomes Study SF-12 (EPIC SF-12) to evaluate patient function and satisfaction after prostate cancer treatment. Response options for each item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL. |
| Health-Related Quality of Life Scores: MAX-PC | Up to 65 months | Health-related quality of life (HRQOL) will be measured using the scores on the Modified 18-item Memorial Anxiety Scale for Prostate Cancer (MAX-PC) from pre-treatment to post-treatment. The scale consists of 18 items (e.g. "I thought about prostate cancer even though I didn't mean to.") scored on a scale from 0 ("not at all") to 3 ("often"). Total scores range from 0 to 54, with higher scores indicating higher levels of anxiety. |
| Health-Related Quality of Life Scores: IPSS | Up to 65 months | Health-related quality of life (HRQOL) will be measured using the International Prostate Symptom Score (IPSS) to evaluate patient urinary function and quality of life. There are 7 questions related to urinary function. Responses are on a scale from 0 ("not at all") to 5 ("almost always"), with higher scores indicating higher levels of urinary dysfunction. There is 1 quality of life question related to urinary symptoms. Responses are on a scale from 0 ("delighted") to 6 ("terrible"). |
| Biochemical and Clinical Failure | Up to 65 months | The cumulative incidence of biochemical or clinical failure allowing for competing risk as needed. Clinical failure is defined as at least a 25% increase in the size of the tumor relative to the smallest volume recorded, or new extension of tumor beyond the capsule, or re-extension of tumor beyond the capsule after initial regression, or urinary obstructive symptoms with carcinoma found at transurethral resection of the prostate (TURP). Biochemical failure is defined as PSA ≥ nadir + 2 ng/mL. |
| Failure-free Survival (FFS) | Up to 65 months | Rate of failure-free survival in study participants. Failure-free survival is defined as the elapsed time from start of radiotherapy to first documented evidence of biochemical or clinical failure or death from any cause, whichever occurs first. In the absence of any event defining failure, follow-up time will be censored at the date of last documented failure-free status. |
| Overall Survival (OS) | Up to 65 months | Rate of overall survival in study participants. Overall survival is defined as the elapsed time from start of radiotherapy to death from any cause. For surviving patients, follow-up will be censored at the date of last contact. |
| Measurement of Tissue Biomarker Expression | Up to 65 months | The distribution and degree of expression of tissue biomarkers by ultrasound-directed biopsies for patients who choose to undergo the optional biopsies. Quantification of the amount of the biomarker specific immunohistochemical staining in the area of tumor. |
| Incidence and Relationship of Circulating DNA and Tumor Cells to Tissue Biomarkers | Up to 65 months | To determine the incidence and relationship of circulating DNA and tumor cells to tissue biomarkers and initial complete biochemical response. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMatthew C Abramowitz, MD
University of Miami
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I: Standard Salvage Radiation Treatment (SSRT) Patients will receive a total dose of 68 Gy will be delivered in 34 fractions to the Clinical Target Volume (CTV), 51 Gy in 34 fractions can be given to the pelvic nodes.
this arm is closed
Standard Salvage Radiation Treatment (SSRT): A total dose of 68 Gy delivered in 34 fractions to the Clinical Target Volume (CTV), 51 Gy in 34 fractions can be given to the pelvic nodes. | 15 |
| Arm II: Mapped Tumor Salvage RT (MTSRT) Patients will receive the same treatment to the CTV of 68 Gy in 34 fractions and the Gross Tumor Volume (GTV) defined by functional imaging will receive 2.25 Gy per day for a total of 76.5 Gy (biological equivalent to 80 Gy in 2.0 Gy fractions assuming an α/β ratio of 3).
this arm was continues as single arm phase 2
Mapped Tumor Salvage RT (MTSRT): Dose escalation to the imaging or Dynamic Contrast Enhanced MRI (DCE-MRI)-defined dominant region(s) by dose painting at 2.25 Gy per fraction, while the rest of the Clinical Target Volume (CTV) receives 2.0 Gy a fraction to 68 Gy. The mapped tumor (MT) boost region will receive an absolute dose of 76.5 Gy. Assuming an α/β ratio of 3.0, this would be equivalent to 80 Gy in 2.0 Gy fractions. | 22 |
| Total | 37 |
Baseline characteristics
| Characteristic | Arm I: Standard Salvage Radiation Treatment (SSRT) | Arm II: Mapped Tumor Salvage RT (MTSRT) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 7 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 15 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 8 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 14 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 18 Participants | 31 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 15 Participants | 22 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 15 | 0 / 22 |
| other Total, other adverse events | 15 / 15 | 21 / 22 |
| serious Total, serious adverse events | 0 / 15 | 4 / 22 |
Outcome results
Primary
PSA Response Rate
Prostate-Specific Antigen (PSA) response rate is defined as the percentage of study patients with PSA less than 0.1 ng/mL at 21 months after completion of study treatment.
Time frame: Up to 23 months
Population: Participants that completed a PSA evaluation at 21 months after completion of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I: Standard Salvage Radiation Treatment (SSRT) | PSA Response Rate | 66.6 percentage of participants |
| Arm II: Mapped Tumor Salvage RT (MTSRT) | PSA Response Rate | 85 percentage of participants |
Secondary
Biochemical and Clinical Failure
The cumulative incidence of biochemical or clinical failure allowing for competing risk as needed. Clinical failure is defined as at least a 25% increase in the size of the tumor relative to the smallest volume recorded, or new extension of tumor beyond the capsule, or re-extension of tumor beyond the capsule after initial regression, or urinary obstructive symptoms with carcinoma found at transurethral resection of the prostate (TURP). Biochemical failure is defined as PSA ≥ nadir + 2 ng/mL.
Time frame: Up to 65 months
Secondary
Failure-free Survival (FFS)
Rate of failure-free survival in study participants. Failure-free survival is defined as the elapsed time from start of radiotherapy to first documented evidence of biochemical or clinical failure or death from any cause, whichever occurs first. In the absence of any event defining failure, follow-up time will be censored at the date of last documented failure-free status.
Time frame: Up to 65 months
Secondary
Health-Related Quality of Life Scores: EPIC SF-12
Health-related Quality of Life (HRQOL) will be measured using the Expanded Prostate Cancer Index Composite and Medical Outcomes Study SF-12 (EPIC SF-12) to evaluate patient function and satisfaction after prostate cancer treatment. Response options for each item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL.
Time frame: Up to 65 months
Secondary
Health-Related Quality of Life Scores: IPSS
Health-related quality of life (HRQOL) will be measured using the International Prostate Symptom Score (IPSS) to evaluate patient urinary function and quality of life. There are 7 questions related to urinary function. Responses are on a scale from 0 (not at all) to 5 (almost always), with higher scores indicating higher levels of urinary dysfunction. There is 1 quality of life question related to urinary symptoms. Responses are on a scale from 0 (delighted) to 6 (terrible).
Time frame: Up to 65 months
Secondary
Health-Related Quality of Life Scores: MAX-PC
Health-related quality of life (HRQOL) will be measured using the scores on the Modified 18-item Memorial Anxiety Scale for Prostate Cancer (MAX-PC) from pre-treatment to post-treatment. The scale consists of 18 items (e.g. I thought about prostate cancer even though I didn't mean to.) scored on a scale from 0 (not at all) to 3 (often). Total scores range from 0 to 54, with higher scores indicating higher levels of anxiety.
Time frame: Up to 65 months
Secondary
Incidence and Relationship of Circulating DNA and Tumor Cells to Tissue Biomarkers
To determine the incidence and relationship of circulating DNA and tumor cells to tissue biomarkers and initial complete biochemical response.
Time frame: Up to 65 months
Secondary
Incidence of Treatment-Emergent Toxicity
Incidence of treatment-emergent toxicity in study participants. Toxicity is defined as adverse events (AEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs)Acute toxicity is defined as toxicity occurring during treatment and within three months of completing treatment. Late toxicity is toxicity occurring more than three months after treatment completion. Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: Up to 8 months
Secondary
Measurement of Tissue Biomarker Expression
The distribution and degree of expression of tissue biomarkers by ultrasound-directed biopsies for patients who choose to undergo the optional biopsies. Quantification of the amount of the biomarker specific immunohistochemical staining in the area of tumor.
Time frame: Up to 65 months
Secondary
Overall Survival (OS)
Rate of overall survival in study participants. Overall survival is defined as the elapsed time from start of radiotherapy to death from any cause. For surviving patients, follow-up will be censored at the date of last contact.
Time frame: Up to 65 months