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Study Summary
No. SWOGS0421:.......Prostate......Ana M. Aparicio......Genitourinary Medical Oncology
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Study Summary Title
Study Summary
Number:
SWOGS0421
Study Title:Phase III Study of Docetaxel and Atrasentan Versus Docetaxel and Placebo for Patients with Advanced Hormone Refractory Prostate Cancer.
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Physician New Patient Referral
Name:Ana M. AparicioPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Genitourinary Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2830
Contact us about clinical trials
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General Information
Disease Group:ProstateSupported By:Southwest Oncology Group
Phase of Study:Phase IIIReturn
Visit:
Patients will return for treatment and follow-up every 3 weeks.
Treatment
Agents:
Atrasentan
Placebo
Prednisone
Taxotere
Home Care:Patients will be responsible for self-administration of the atrasentan/placebo
pills.
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
n/a
Description/
Intervention:
The goal of this clinical research study is to compare the combination of
atrasentan, docetaxel, and prednisone to the combination of docetaxel and
prednisone (plus a placebo) in the treatment of advanced prostate cancer that
has spread to the bone. The safety of this drug combination will also be
studied.
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Study Objectives / Outcomes
Primary objectives:
  • The co-primary objectives are to compare survival and progression-free survival in patients with hormone refractory metastatic prostate cancer involving bone (with or without soft tissue disease) randomized between atrasentan versus placebo, combined with docetaxel and prednisone.

Secondary objectives include:
  • To compare pain progression between the two study arms.
  • To compare qualitative and quantitative toxicity between the two study arms.
  • To compare elements of Quality of Life (QOL) between treatment arms, primarily:
    a. Palliation of metastatic bone pain.
    b. Improvement in functional status.
  • To compare prostate specific antigen (PSA) response rates between the experimental arm and the standard arm.
  • To compare objective responses between the two treatment groups in patients with measurable disease as defined by RECIST criteria.
  • To record serum prostate specific antigen (PSA) and collect serum markers of bone resorption (N-telopeptide, deoxypyridinoline, and pyridinoline) and bone formation (osteocalcin, procollagen I and III amino-terminal propeptides, total alkaline phosphatase and bone alkaline phosphatase) for future correlations with response and survival.
  • To prospectively test whether a 30% reduction in PSA and the slope of PSA from baseline to three months post-randomization is a surrogate marker for survival in this clinical trial.
  • To evaluate the association of PSA progression with subsequent clinical progression and death.
  • To acquire serum, genomic DNA and tissue tumor specimens from patients on this clinical trial for relevant genetic polymorphism and p27 studies for future correlative studies.
  • To assess the predictive and prognostic role of enumeration and expression analysis of circulating tumor cells (CTCs) in these patients. To compare the difference in prognostic association of CTCs and clinical outcomes using two different technologies for measuring CTCs.
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Study Status Information
Study Activation / Registration Date:07/31/2009
IRB Review and Approval Date:05/01/2009
Study Type:Phase Iii
Recruitment Status:Terminated
Projected Accrual:930
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) All patients must have a histologic diagnosis of adenocarcinoma of the prostate which is measurable or non-measurable, Stage any T, any N, M1b and have evidence of bone metastases on bone scan. In a case, where a bone scan result is considered equivocal, then magnetic resonance imaging should be used to discriminate between malignant and other causes of bone scan abnormality. However, MRI will not be routinely incorporated into progression/response assessment. All disease must be assessed and documented on the Baseline Tumor Assessment Form

2) Patients 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 antiandrogen withdrawal when applicable) : a) Progression of measurable disease assessed within 28 days prior to registration; b) Progression of non-measurable disease (i.e., bone scan) assessed within 28 days prior to registration;

3) (# 2 Cont'd) c) Rising PSA - Rising PSA is defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1). The first rising PSA (measure 2) must be taken at least 7 days after the reference value. A third confirmatory PSA measure is required (2nd beyond the reference level) to be greater than the second measure, and it must be obtained at least 7 days after the 2nd measure. If this is not the case, a fourth PSA is required to be taken and be greater than the second measure.

4) (# 2c cont'd) The patient must have a PSA >/= 5 ng/ml in addition to increasing PSA to be eligible by rising PSA criteria alone. However, no minimum PSA is required for patients whose progression is based on measurable or non-measurable disease.

5) All patients must have a prestudy PSA obtained within 28 days prior to registration.

6) All patients must have had a CT scan or MRI of the abdomen and pelvis within 28 days prior to registration. Patients must also have had a bone scan within 28 days prior to registration.

7) Patients must be offered the opportunity to participate in specimen banking for future use (to include the serum and tissue correlative studies, and CTC measures).

8) Patients must have been surgically or medically castrated. If method of castration is luteinizing hormone-releasing hormone (LHRH) agonists (leuprolide or goserelin) or LHRH antagonists, then the patient should be willing to continue the use of LHRH agonists. Castration using LHRH agonist should not be interrupted and patients who have stopped treatment should be willing to restart.

9) If the patient has been treated with non-steroidal antiandrogens (flutamide, bicalutamide, nilutamide or ketoconazole), effective 3/15/08 they must have been stopped at least 14 days prior to registration for ketoconazole and at least 28 days prior to registration for flutamide, bicalutamide or nilutamide and the patients must have demonstrated progression

10) Prior radiation therapy (to less than 30% of the bone marrow only) is allowed. This includes prior use of samarium, but patients can not have received prior strontium. At least 21 days must have elapsed since the completion of radiation therapy and the patient must have recovered from side effects. Soft tissue disease which has been radiated in the prior 2 months is not assessable as measurable disease.

11) Patients may have received prior surgery. However, at least 21 days must have elapsed since completion of surgery and patient must have recovered from all side effects.

12) One prior systemic therapy (vaccine or biologic therapy) is allowed and at least 28 days must have elapsed since completion of therapy and patient must have recovered from all side effects. Prior therapy must not have included cytotoxic chemotherapy for metastatic prostate cancer. Prior adjuvant therapy with a single non-taxane containing cytotoxic regimen is permitted provided more than 2 years has elapsed since its completion.

13) Patients are permitted to take bisphosphonates provided they began bisphosphonate therapy before registration to S0421, they fulfill criteria for disease progression, and that they continue them as per the manufacturer's guidelines and/or as per institutional practice. Patients not taking ongoing bisphosphonate therapy will not be permitted to start such therapy until they have completed 12 weeks of study treatment.

14) Patients must be able to take oral medication without crushing, dissolving or chewing tablets.

15) Patients must discontinue herbal medications and food supplements (e.g., PC-Spes, Saw Palmetto, St. John's Wort, etc.) before registration. Patients may continue on daily vitamins and calcium supplements.

16) Patients must have hemoglobin and alkaline phosphatase obtained within 28 days prior to registration.

17) Serum testosterone must be obtained within 28 days prior to registration.

18) Patients must not have </= Grade 2 Symptomatic Neuropathy Sensory (NCI-Common Terminology Criteria for Adverse Events).

19) Patients must not have a history of hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80.

20) Patients must have a Zubrod performance status of 0 - 3. For those patients with PS of 3, the cause must be due to pain secondary to bone metastases in order to be eligible.

21) No other chemotherapeutic, biological response modifiers, radiation therapy, corticosteroid or hormonal concomitant therapy (other than continuing LHRH treatment and/or bisphosphonate therapy) may be planned to be given during protocol treatment. Prior or concomitant use of megestrol acetate for the treatment of hot flashes is allowed.

22) Patients receiving finasteride, dutasteride, or other 5 alpha reductase inhibitors for the treatment of benign prostatic hypertrophy (BPH) are eligible provided treatment is clearly documented for BPH. Patients on finasteride, dutasteride or other 5 alpha reductase inhibitors for indications apart from BPH must discontinue them prior to registration.

23) Patients must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have significant active concurrent other medical illness precluding protocol treatment or survival.

24) All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:1) Prohibited medications: Docetaxel is a moderate to significant in vitro inhibitor of CYP3A4. The following lists of medications/substances are moderate to significant inhibitors/inducers of CYP3A4 that, if administered concomitantly with docetaxel, may alter study drug exposure. The use of these medications/ substances within 14 days (</= 6 months for amiodarone) prior to the administration of the first dose of docetaxel through discontinuation of docetaxel is prohibited. Inhibitors of CYP3A4: a) Antibiotics: Clarithromycin, erythromycin, troleandomycin, rifampin, rifabutin, rifapentine;

2) (#2 cont'd) b) Antifungals: itraconazole, ketoconazole, fluconazole (doses > 200 mg/day), voriconazole; c) Antidepressants: nefazodone, fluovoxamine; d) Calcium channel blockers: verapamil, diltiazem; d) Miscellaneous: amiodarone*, grapefruit juice, bitter orange *Use of amiodarone within 6 months prior to the administration of the first dose of docetaxel is prohibited. Inducers of CYP3A4: a) Anticonvulsants: phenytoin, carbamazepine, phenobarbital, oxcarbazepine b) Antibiotics: rifampin, rifabutin, rifapentine c) Miscellaneous: St. John's Wort, modafinil

3) Patients with a history of brain metastases or who currently have treated or untreated brain metastases are not eligible. Patients with clinical evidence of brain metastases must have a brain CT or MRI negative for metastatic disease within 56 days prior to registration.

4) Patients with third space fluid accumulation such as ascites or symptomatic pleural effusion are not eligible.

5) No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years.

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Links
Registration Number: NCT00134056
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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