Multimodality Phase II Study in Prostate Cancer

• Status: Terminated
• Trial end date: 2014-11-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Collaborators: Pfizer; Sanofi
• Treatments: Docetaxel; Sunitinib

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