Clinical trial NCT00734851: Multimodality Phase II Study in Prostate Cancer
Official title: Multimodality Therapy for Recurrent High Risk Prostate Cancer: A Phase II Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: prostate cancer
sunitinib
docetaxel
PSA
radiation
PSA recurrence
No metastatic disease
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Sanofi
First posted: 2008-08-14
Enrollment: 36
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: This is a single arm phase II study of docetaxel, prednisone, and sunitinib systemic therapy followed by salvage external beam radiation therapy for men who have experienced PSA recurrence following initial radical prostatectomy for prostate cancer. The primary aim is the rate of progression-free survival at 2 years as measured by lack of PSA progression and no evidence of disease. We hypothesize that this aggressive initial systemic therapy will improve the long term remission rates for men who are undergoing salvage radiation therapy for PSA recurrence in the absence of metastatic disease.

Detailed description: In many common malignancies such as breast cancer, trimodality therapy represents the standard-of-care approach, including initial surgical resection followed by systemic chemotherapy followed by radiotherapy for optimal local control, and targeted hormonal or biologic therapy for a period of time to reduce the ongoing risk of systemic disease recurrence. These approaches have reduced recurrence rates and improved overall survival in the adjuvant setting in breast cancer; however, the treatment of men with PSA recurrence following radical prostatectomy has generally been unsatisfying, given the high rates of persistent or recurrent disease despite salvage radiotherapy.

The primary purpose of the study is to determine the rate of biochemical (PSA) progression free survival (bPFS) in men with PSA recurrent non-metastatic prostate cancer following radical prostatectomy, who receive multimodality therapy consisting of local salvage external beam radiotherapy and systemic docetaxel-based chemotherapy plus the targeted anti-VEGF biologic therapy sunitinib. Biochemical PFS will be defined as the proportion of subjects at 24 months, post-registration, with one of the following: 1) a serum PSA value of 0.2 ng/ml or more above the post-radiotherapy PSA nadir and confirmed 4 weeks later by a second PSA measurement that was higher than the first by any amount, 2) a continued rise in the PSA level following study treatment if no nadir is experienced, defined as 2 rising values greater than the baseline PSA and separated by at least 4 weeks, 3) evidence of clinical progression or initiation of systemic therapy for progressive disease, or 4) death. Secondary objectives include finding the rate of biochemical (PSA) disease free survival over time, Two-, three-, five-, and six- year risk of local recurrence (proportion), two-, three-, five-, and six-year risk of metastases and metastasis-free survival, two-, three-, five-, and six-year risk of metastases and metastasis-free survival, Safety, feasibility, and tolerability as assessed by NCI Common Toxicity Scales (v3.0), quality of life questionnaire (EPIC-short form surveys), achievement of accrual goals. Finally, a comparison of RNA expression profiles from original prostate radical prostatectomy specimen among those with PSA relapse at 2 and 5 years as compared to those without PSA relapse at the primary endpoint.

Eligibility criteria: Inclusion Criteria:

1. Prostate adenocarcinoma with evidence of recurrent disease as measured only by rising PSA, without evidence of metastatic disease by bone scan or CT scan within 4 weeks of entry
2. PSA ≤ 3.0 ng/ml and ≥ 0.1 ng/ml within 2 weeks of registration
3. Radical prostatectomy within 4 years of registration.
4. Rising PSA as defined by 1 or more PSA values greater than the nadir value after radical prostatectomy, separated by at least 4 weeks.
5. Gleason sum at radical prostatectomy of 7-10 (4+3 or 3+4 allowed)
6. Informed consent
7. Age \> 18 years.
8. Adequate laboratory parameters:

   * leukocytes ≥ 3,000/uL
   * absolute neutrophil count ≥ 1,500/uL
   * platelets ≥ 75,000/uL
   * hemoglobin \> 9.0 g/dl
   * total bilirubin within normal institutional limit
   * AST(SGOT)/ALT(SGPT) \< 2.5x institutional upper limit
   * creatinine \< 2.0x institutional upper limit
9. Karnofsky Performance Status ≥ 80 (Attachment 2).
10. Written, signed, dated, and witnessed IRB approved informed consent form (ICF) before any screening procedures are performed.
11. Peripheral neuropathy ≤ grade 1

Exclusion Criteria:

1. Evidence of metastatic disease by CT scan, physical exam, or bone scan within 4 weeks of registration
2. History of bleeding disorders or medical comorbidities that in the opinion of the investigator would preclude the use of systemic chemotherapy
3. Prior systemic or biologic therapy, including pre-operative therapies or adjuvant chemotherapy, biologic therapy, or hormonal therapy
4. Life expectancy of less than 5 years from medical co-morbidities by physician judgment
5. Non-adenocarcinoma prostate cancer pathology at radical prostatectomy
6. Prior radiotherapy to the abdomen or pelvis
7. Less than or equal to 6 weeks from prior major surgery, including radical prostatectomy, open biopsy, or traumatic injury.
8. Recent cardiovascular event (within 12 months) including unstable angina, myocardial infarction, severe or at rest claudication, or stroke/CVA.
9. Subjects receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers. Subjects on acceptable CYP3A4 isoenzyme inhibitors and/or inducers are eligible, provided they have been taking a stable regimen for at least 4 weeks prior to screening.
10. Presence of a non-healing wound or ulcer.
11. Grade \>= 3 hemorrhage within the past month.
12. Hypertension with systolic blood pressure of \>140 mm Hg and/or diastolic pressure \>90 mm Hg at the time of screening. Anti-hypertensive medications are permitted.
13. Subjects with American Heart Association (AHA) Class 2-4 heart disease or any history of congestive heart failure with an ejection fraction \<50%.
14. Subjects with inability to tolerate or absorb oral medications.
15. QTc interval \>480 msec on baseline EKG. Subjects may not be taking a medication known to significantly prolong the QTc interval.
16. Subjects who have not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy.
17. Anticoagulation with warfarin (therapeutic doses of warfarin for catheter patency are permitted). Low molecular weight heparin is permitted.
18. Active infection(s), active antimicrobial therapy or serious intercurrent illness.
19. Any other major medical or psychiatric illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study, including inability to absorb oral medications.
20. Any history of hemoptysis within the past 12 months

Primary outcomes:
measure: The Rate of Progression Free Survival (PFS) at 24 Months
timeFrame: 2 years
Secondary outcomes:
measure: Proportion of Biochemical Progression (bPFS Proportion) at 2 and 3 Years.
timeFrame: 24 months and 36 months
measure: Rate of Local Recurrence at 2 and 3 Years
timeFrame: 24 months and 36 months
measure: Metastasis-free Survival (MFS) Rates at 2 and 3 Years.
timeFrame: 2 and 3 years
measure: Change in Quality of Life (QoL) After 1 Year
timeFrame: baseline and 1 year
measure: Change in Quality of Life (QoL) After 3 Month
timeFrame: baseline and 3 months
measure: Comparison of RNA Expression Profile From Original Prostate Radical Prostatectomy Specimen Among Those With PSA Relapse at 2 and 3 Years as Compared to Those Without PSA Relapse at the Primary Endpoint.
timeFrame: 2 and 3 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: New Brunswick
country: United States
facility: The Cancer Institute of New Jersey
state: New Jersey
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Duke University
name: Andrew J Armstrong, MD, ScM
role: PRINCIPAL_INVESTIGATOR
References: