Multimodality Phase II Study in Prostate Cancer | NCT00734851

NCT00734851

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Pfizer	INDUSTRY
Sanofi	INDUSTRY

Description Module

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.

Label	Type	Description	Intervention Names
Multimodality	Experimental	4 cycles of 70 mg/m2 Docetaxel + 37.5 mg daily Sunitinib for 14 days followed by a 7 day break for 3 cycles + external beam radiotherapy to 66 Gray over 6-7 weeks	Drug: Docetaxel Drug: Sunitinib Radiation: EBXRT

Name	Type	Description	Arm Group Labels	Other Names
Docetaxel	Drug	Docetaxel 70 mg/m2 day 1 every 3 weeks for 4 cycles with prednisone 5 mg orally twice daily	Multimodality

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
The Rate of Progression Free Survival (PFS) at 24 Months	Percentage of participants surviving 24 months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression. Progression will be defined as having experienced any of the following: a serum prostate specific antigen (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, 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, or evidence of clinical progression or initiation of systemic therapy for progressive disease.	2 years

Secondary Outcomes

Measure	Description	Time Frame
Proportion of Biochemical Progression (bPFS Proportion) at 2 and 3 Years.	Percentage of participants surviving 24 and 36 months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression. Progression will be defined as having experienced any of the following: a serum prostate specific antigen (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 or 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. Please note: bPFS is identical to PFS but includes only PSA-based endpoints or death.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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
PSA ≤ 3.0 ng/ml and ≥ 0.1 ng/ml within 2 weeks of registration
Radical prostatectomy within 4 years of registration.
Rising PSA as defined by 1 or more PSA values greater than the nadir value after radical prostatectomy, separated by at least 4 weeks.
Gleason sum at radical prostatectomy of 7-10 (4+3 or 3+4 allowed)
Informed consent
Age > 18 years.
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
Karnofsky Performance Status ≥ 80 (Attachment 2).
Written, signed, dated, and witnessed IRB approved informed consent form (ICF) before any screening procedures are performed.
Peripheral neuropathy ≤ grade 1

Exclusion Criteria:

Evidence of metastatic disease by CT scan, physical exam, or bone scan within 4 weeks of registration
History of bleeding disorders or medical comorbidities that in the opinion of the investigator would preclude the use of systemic chemotherapy
Prior systemic or biologic therapy, including pre-operative therapies or adjuvant chemotherapy, biologic therapy, or hormonal therapy
Life expectancy of less than 5 years from medical co-morbidities by physician judgment
Non-adenocarcinoma prostate cancer pathology at radical prostatectomy
Prior radiotherapy to the abdomen or pelvis
Less than or equal to 6 weeks from prior major surgery, including radical prostatectomy, open biopsy, or traumatic injury.
Recent cardiovascular event (within 12 months) including unstable angina, myocardial infarction, severe or at rest claudication, or stroke/CVA.
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.
Presence of a non-healing wound or ulcer.
Grade >= 3 hemorrhage within the past month.
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.
Subjects with American Heart Association (AHA) Class 2-4 heart disease or any history of congestive heart failure with an ejection fraction <50%.
Subjects with inability to tolerate or absorb oral medications.
QTc interval >480 msec on baseline EKG. Subjects may not be taking a medication known to significantly prolong the QTc interval.
Subjects who have not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy.
Anticoagulation with warfarin (therapeutic doses of warfarin for catheter patency are permitted). Low molecular weight heparin is permitted.
Active infection(s), active antimicrobial therapy or serious intercurrent illness.
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.
Any history of hemoptysis within the past 12 months

Name	Affiliation	Role
Andrew J Armstrong, MD, ScM	Duke University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Johns Hopkins University		Baltimore	Maryland	21218	United States
The Cancer Institute of New Jersey

ID	Title	Description
FG000	Multimodality	4 cycles of 70 mg/m2 Docetaxel + 37.5 mg daily Sunitinib for 14 days followed by a 7 day break for 3 cycles + external beam radiotherapy to 66 Gray over 6-7 weeks

ID	Title	Description
BG000	Multimodality	4 cycles of 70 mg/m2 Docetaxel + 37.5 mg daily Sunitinib for 14 days followed by a 7 day break for 3 cycles + external beam radiotherapy to 66 Gray over 6-7 weeks

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

The Rate of Progression Free Survival (PFS) at 24 Months

Percentage of participants surviving 24 months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression. Progression will be defined as having experienced any of the following: a serum prostate specific antigen (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, 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, or evidence of clinical progression or initiation of systemic therapy for progressive disease.

Posted

Number

95% Confidence Interval

percentage of patients

2 years

ID	Title	Description
OG000	Multimodality

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Multimodality	4 cycles of 70 mg/m2 Docetaxel + 37.5 mg daily Sunitinib for 14 days followed by a 7 day break for 3 cycles + external beam radiotherapy to 66 Gray over 6-7 weeks

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic