Clinical trial NCT00879619: Taxotere/Prednisone Plus Sunitinib in Chemotherapy-Naïve, Hormone Refractory Prostate Cancer Patients
Official title: A Pilot Phase I/II Study to Evaluate the Effects of Taxotere/Prednisone Plus Sunitinib in Chemotherapy-Naïve, Hormone Refractory Prostate Cancer Patients With Biochemical Relapse
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Adenocarcinoma of the Prostate
Recurrent Prostate Cancer
Stage I Prostate Cancer
Stage III Prostate Cancer
Stage IV Prostate Cancer
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2009-04-10
Enrollment: 4
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: RATIONALE: Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving docetaxel and prednisone together with sunitinib malate may kill more tumor cells.

PURPOSE: This pilot phase I/II trial studies the side effects and best way to give docetaxel and prednisone together with sunitinib malate and to see how well it works in treating patients with prostate cancer that progressed after hormone therapy.

Detailed description: PRIMARY OBJECTIVES:

I. To evaluate the response by prostate specific antigen (PSA) of docetaxel/prednisone plus sunitinib (sunitinib malate) in chemotherapy-naive, hormone refractory prostate cancer subjects with biochemical relapse.

SECONDARY OBJECTIVES:

I. To determine the objective response rate (ORR) and duration of response (DR) in subjects with measurable disease.

II. To determine overall survival (OS) and time to progression (TTP). III. To evaluate the safety and tolerability of sunitinib in combination with docetaxel and prednisone.

OUTLINE:

Patients receive docetaxel intravenously (IV) over 60 minutes on day 1, prednisone orally (PO) twice daily (BID) on days 1-21, and sunitinib malate PO once daily (QD) on days 2-15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients then receive sunitinib malate PO QD on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 3 years.

Eligibility criteria: Inclusion Criteria

* Subjects must have a histological diagnosis of adenocarcinoma of the prostate
* Age ≥ 18
* Subjects must have metastatic prostate cancer deemed to be unresponsive or refractory to hormone therapy by one or more of the following (despite androgen deprivation and anti-androgen withdrawal when applicable) check all that apply.
* Subjects may have received prior surgery. However, at least 21 days must have elapsed since completion of surgery and Subject must have recovered from all side effects.
* Subjects must have adequate hepatic function as defined by:
* a serum bilirubin ≤1.5 x the institutional upper limit of normal (IULN),
* Serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) ≤2.5 x the institutional upper limit of normal obtained within 14 days prior to start of therapy
* Subjects must have 2 pre-study PSA \> 2ng/ml at least 1 week apart within 28 days prior to start of therapy
* Subjects must have been surgically or medically castrated. If method of castration is luteinizing hormone-releasing hormone (LHRH) agonist (leuprolide or goserelin), then the Subject should be willing to continue the use of LHRH agonists. Castration using LHRH agonist should not be interrupted and subjects who have stopped treatment should be willing to restart.
* Subjects must not take vitamins, herbs, or micronutrient supplement within 28 days prior to start of therapy.
* Prior external beam radiation therapy (to less than 30% of the bone marrow only) is allowed. This includes prior use of samarium, but subjects can not have received prior strontium. At least 28 days must have elapsed since the completion of radiation therapy and the Subject must have recovered from side effects. Soft tissue disease which has been radiated in the prior 2 months is not assessable as measurable disease.
* Subjects with a history of myocardial infarction are not eligible. Subjects must have a baseline EKG to rule out underlying cardiac disease within 42 days prior to registration. Subjects with a history of cardiac disease, specifically congestive heart failure (CHF) are ineligible unless their disease is well-controlled. Subjects with history of cardiovascular accident (CVA) or atrial fibrillation are ineligible.
* Subjects with a history of brain metastases or who currently have treated or untreated brain metastases are not eligible. Subjects with clinical evidence of brain metastases must have a brain CT or MRI negative for metastatic disease within 56 days prior to registration.

  \*Liver function tests should be evaluated prior to each treatment.
* Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* Subjects must have an adequate renal function as defined by:
* a serum creatinine ≤1.5 x the institutional upper limit of normal obtained within 14 days prior to start of therapy and a urine protein: creatinine (UPC) ratio of ≤ 1.0.
* Subjects must have the following hematological criteria (minimal values):
* Absolute neutrophil count ≥ 1,500/mm³
* Hemoglobin of ≥ 8.0gm/dL,
* White blood cell count ≥ 2500,
* Platelets ≥ 75,000/mm³
* Subjects must be able to take oral medications

Exclusion Criteria

* Subjects must not have received chemotherapy, biologic therapy or any other investigational drug for any reason within 28 days prior to start of therapy and must have recovered from toxicities of prior therapy to grade 1 or less with the exception of alopecia.
* Subjects may not have ongoing problems with bowel obstruction or short bowel syndrome characterized by grade 2 or greater diarrhea or malabsorptive disorders.
* Men of child bearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
* Subjects with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 will be excluded
* Subjects should not have psychological, familial, sociological, or geographical conditions that do not permit medical follow-up or compliance with the study protocol.
* Subjects should not have any medical life-threatening complications of their malignancies
* Subjects should not have a known severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, active uncontrolled infection, or HIV).
* Subjects should not have current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.
* Baseline blood pressure of \< or equal to 150/100 mmHg. Subjects with a blood pressure reading above this level should be initiated on anti-hypertensive therapy and may be considered for protocol treatment when their blood pressure is adequately controlled.
* Subjects with New York Heart Association (NYHA) Grade II or greater congestive heart failure are not eligible. Subjects must have a baseline multiple gated acquisition scan (MUGA) or Echocardiogram with a calculated ejection fraction \> or equal to 50%.
* Subjects with clinically significant peripheral vascular disease are not eligible.
* Subjects with evidence of bleeding diathesis or coagulopathy are not eligible.
* Subjects with central nervous system or brain metastases are not eligible.
* Subjects who had major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study are not eligible.
* Subjects with minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0 are not eligible.
* Subjects with history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess are not eligible.
* Subjects with serious, non-healing wound, ulcer, or bone fracture are not eligible.
* Subjects who are diagnosed of any other malignancy except non-melanomatous skin cancer in the past 5 years are not eligible.
* Subjects receiving anticoagulation therapy (e.g. Coumadin) prior to registration are not eligible. Subjects are permitted to have prior Coumadin for prophylaxis against agents that might produce blood clots. Subjects with low dose Aspirin (86mg) are acceptable.
* Subjects with active thrombophlebitis or hypercoagulability are not eligible. Subjects with known history of pulmonary embolus are not eligible.
* All Subjects must be informed and must sign and give written informed consent in accordance with institutional and federal guidelines. Subjects who are unable to comply with study and/or follow-up procedures are not eligible.

Primary outcomes:
measure: Prostate Specific Antigen (PSA) Response Rate
timeFrame: Baseline, every 3 weeks, at study termination, and then for 3 years
Secondary outcomes:
measure: Rates of Tumor Response (ORR)
timeFrame: Every 2 months
measure: Duration of Response (DR)
timeFrame: Up to 3 years
measure: Time to Progression (TTP) by PSA Response and Disease Response
timeFrame: Baseline, every 3 weeks, at study termination, and then for 3 years
measure: Survival
timeFrame: At 2 and 3 years
measure: Qualitative and Quantitative Toxicity
timeFrame: Every 3 weeks and at study termination
Other outcomes:
Locations:
city: Orange
country: United States
facility: Chao Comprehensive Cancer Center
state: California
Study officials:
affiliation: Chao Family Comprehensive Cancer Center
name: John P Fruehauf, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: