Clinical trial NCT03822494: CyberKnife Dose Escalation Prostate Cancer Trial
Official title: CyberKnife Dose Escalation for Unfavorable and High-risk Prostate Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Prostate Cancer
Prostate Adenocarcinoma
Prostate Neoplasm
Keywords: radiation therapy
Cyberknife
SBRT
Protons
Lead sponsor: Crozer-Keystone Health System
Sponsor class: OTHER
First posted: 2019-01-30
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Stereotactic body radiation therapy (SBRT) has been employed in the treatment of prostate cancer. Multiple single institution experiences suggest high biochemical control rates with acceptable toxicity in low risk prostate cancer but efficacy data in unfavorable type prostate cancer is less convincing. CyberKnife-SBRT (CK-SBRT) can be used to escalate radiation dose delivery to the prostate while sparing normal tissue.

Detailed description: The optimal radiation schedule for the curative treatment of prostate cancer remains unknown. Prostate cancer patients receiving radiation therapy are typically treated 5 days per week for 8-9 weeks. Recent data suggest that large radiation fraction sizes are radio-biologically favorable over lower fraction sizes in prostate cancer radiotherapy. The sensitivity of a tumor or normal tissue to fraction size of radiation can be approximated by the alpha-beta ratio. It has been suggested that the alpha/beta ratio for prostate cancer is actually as low as 1.5 implying that the current radiation therapy paradigm for prostate cancer treatment might be fundamentally flawed, as high fraction sizes would be expected to damage tumor more readily.

Typical prostate SBRT doses do not appear to have similar efficacy in higher risk prostate cancer suggesting even higher doses are required. Many techniques including dose escalated external beam radiation therapy (EBRT), proton therapy (PT) and brachytherapy have been employed to increase dose to the prostate. Data from the ASCEND-RT trial utilizing low dose rate brachytherapy boost showed a dramatic 21% improvement in biochemical control at 9 years favoring brachytherapy boost compared to conventional dose escalated EBRT radiation therapy. However, no corresponding benefit was identified in overall survival, incidence of bone metastases or prostate cancer specific mortality while a 3 fold increase in late urinary toxicity was noted.

SBRT is well tolerated with minimal acute and late side effects. In this protocol, CK-SBRT will be used to target the microscopic and gross disease in the prostate, seminal vesicles. An escalated dose of 40 Gy in 5 fractions will be delivered to the entire target volume while any nodules visible within the prostate gland on endorectal MRI will receive 50 Gy in 5 fractions.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed adenocarcinoma of the prostate diagnosed within 360 days of enrollment.
* Prostate Specific Antigen (PSA) documented within 90 days prior to registration.
* Clinical staging completed within 90 days of registration.
* No Nodal or Distant Metastases documented on CT or MRI of the pelvis and bone scan.
* Unfavorable Risk Prostate Carcinoma as Described is documented.
* No prior pelvic radiotherapy.
* No prior Trans-urethral resection of the prostate (TURP).
* Prostate volume \< 100 cc
* American Urologic Association (AUA) score \< 20
* No recent (within 5 years) or concurrent cancers other than non-melanoma skin cancers.
* Patient must have no medical or psychiatric illnesses that would interfere with treatment or follow-up.
* No implanted hardware adjacent to the prostate that would prohibit appropriate treatment planning and treatment delivery is allowed.
* Candidate for rectal spacer placement

Exclusion Criteria:

* Other cancer diagnosis other than non-melanoma skin cancer with 5 years
* Prostate size greater than 100cc
* AUA greater than 20
* Implanted hardware impacting imaging
* Metastatic prostate cancer
* Contraindication to hormone therapy

Primary outcomes:
measure: Bladder and Rectal Toxicity using NCI common toxicity criteria version 4.0
timeFrame: 24 Months
Secondary outcomes:
measure: Biochemical Disease Free Survival
timeFrame: 24 Months
measure: Duration of local control
timeFrame: 24 Months
measure: Distant Failure
timeFrame: 24 Months
measure: Disease Free Survival
timeFrame: 24 Months
measure: Disease Specific Survival
timeFrame: 24 Months
measure: Overall Survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Philadelphia CyberKnife
state: Pennsylvania
Study officials:
affiliation: Philadelphia CyberKnife -Crozer Health
name: Rachelle Lanciano, MD
role: STUDY_CHAIR
affiliation: Philadelphia CyberKnife -Crozer Health
name: Rachelle Lanciano, MD
role: PRINCIPAL_INVESTIGATOR
References: