Multimodality Phase II Study in Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Pfizer
Sanofi
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00734851
First received: August 13, 2008
Last updated: August 29, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: Docetaxel
Drug: Sunitinib
Radiation: EBXRT
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multimodality Therapy for Recurrent High Risk Prostate Cancer: A Phase II Study

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • The primary objective is the rate of progression free survival (PFS) at 24 months [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Biochemical (PSA) progression free survival over time and the proportion progression free (bPFS proportion) at 2 and 3 years. bPFS is identical to PFS but includes only PSA-based endpoints or death. [ Time Frame: 2 and 3 years ] [ Designated as safety issue: No ]
  • Local recurrence will be defined as men with locally recurrent disease confirmed pathologically within the radiation field, and will be estimated at 2 and 3 years. [ Time Frame: 2 and 3 years ] [ Designated as safety issue: No ]
  • Metastasis-free survival (MFS) rates at 2 and 3 years. Metastasis-free survival will be defined as the date of registration to date of evidence of systemic disease on bone scan or cross sectional imaging or death, which occurs first. [ Time Frame: 2 and 3 years ] [ Designated as safety issue: No ]
  • Safety, feasibility, and tolerability as assessed by NCI Common Toxicity Scales (v3.0), quality of life (EPIC survey), and achievement of accrual goals. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: 2 and 3 years ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: December 2008
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Docetaxel
    Docetaxel 70 mg/m2 day 1 every 3 weeks for 4 cycles with prednisone 5 mg orally twice daily
    Other Name: Taxotere
    Drug: Sunitinib
    Sunitinib 37.5 mg orally once daily for 14 days followed by 7 days off, for 4 cycles, concurrent with docetaxel and prednisone
    Other Name: Sutent
    Radiation: EBXRT
    External beam radiotherapy to the prostate bed, started on day 100, after completion of chemotherapy. 66 Gy over 6-7 weeks.
    Other Name: IMRT
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00734851

Locations
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21218
United States, New Jersey
The Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Duke University
Pfizer
Sanofi
Investigators
Principal Investigator: Andrew J Armstrong, MD, ScM Duke University
  More Information

No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00734851     History of Changes
Other Study ID Numbers: Pro00010747
Study First Received: August 13, 2008
Last Updated: August 29, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Duke University:
prostate cancer
sunitinib
docetaxel
PSA
radiation
PSA recurrence
No metastatic disease

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Docetaxel
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014