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Study Using IMC-A12 or IMC-1121B Plus Mitoxantrone and Prednisone in Metastatic Androgen-Independent Prostate Cancer, Following Disease Progression on Docetaxel-Based Chemotherapy
Basic Trial Information
Summary The purpose of this study is to determine whether IMC-A12 or IMC-1121B with Mitoxantrone and Prednisone is effective in the treatment of metastatic androgen- independent prostate cancer. Further Study Information Prostate cancer is the most frequently diagnosed cancer in men and the second leading cause of cancer-related death in men in the United States. Chemotherapy, either as a single agent or in combination, may lead to clinical response, pain control, and/or improved quality of life. Docetaxel is now the first-line standard therapy for AIPC. Mitoxantrone was approved in 1996 for use in combination with corticosteroids as initial chemotherapy for pain related to advanced HRPC. Hormonal manipulations and docetaxel-based chemotherapy are often effective in metastatic prostate cancer; however, disease becomes refractory to these interventions in the majority of men. Although mitoxantrone continues to be a significant agent in the treatment of HRPC, there exists a need for more efficacious therapy in docetaxel-refractory- AIPC. Because of the potential contribution of IGF-IR and VEGFR-2 mediated pathways in prostate cancer pathogenesis, it is hypothesized that each of these biological agents in combination with mitoxantrone and prednisone will result in clinically meaningful activity in AIPC. Therefore, ImClone plans to conduct a randomized Phase 2 trial to assess the safety and efficacy of IMC-A12 or IMC-1121B in combination with mitoxantrone and prednisone in patients with AIPC. Eligibility Criteria Inclusion Criteria: 1. The patient has histologically-confirmed adenocarcinoma of the prostate. 2. The patient has radiographic evidence of metastatic prostate cancer (stage M1 or D2). 3. The patient has prostate cancer unresponsive or refractory to hormone therapy (androgen-independent). 4. The patient has had disease progression (clinical or radiographic) while receiving docetaxel, or within 120 days of receiving docetaxel-based chemotherapy and in the opinion of the investigator is unlikely to derive significant benefit from additional docetaxel-based therapy, or was intolerant to therapy with this agent. 5. The patient must have evidence of progressive disease defined as at least one of the following;a. Progressive measurable disease: using conventional solid tumor criteria b. Bone scan progression: at least two new lesions on bone scan c. Increasing PSA: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2. 6. The patient has a PSA ≥ 2 ng/mL. 7. The patient has prior surgical or medical castration with a serum testosterone of <50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the patient must be willing to continue the use of LHRH agonists during protocol treatment. 8. All clinically significant toxic effects (excluding alopecia) of prior surgery,radiotherapy, or hormonal therapy have resolved to ≤ Grade 1 based on the NCI-CTCAE v 3.0, with the exception of peripheral neuropathy, which must have resolved to Grade ≤ 2. 9. The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2. 10. The patient has adequate hematologic function (absolute neutrophil count [ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL). 11. The patient has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal (ULN)], aspartate transaminase [AST] and alanine transaminase [ALT]≤ 3 times the ULN, or ≤ 5 times the ULN if liver metastases are present). 12. The patient has adequate renal function (creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 40 mL/min). 13. The patient's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study. 14. The patient has adequate coagulation function (an international normalized ratio [INR] ≤ 1.5 and a partial thromboplastin time [PTT] ≤ 5 seconds above the ULN [unless on oral anticoagulant therapy]). Patients receiving full-dose anticoagulation therapy are eligible provided they meet all other criteria, are on a stable dose of oral anticoagulant or low molecular weight heparin (and if on warfarin have a therapeutic INR between 2 and 3). 15. The patient has a fasting serum glucose level of < 160 mg/dL, or below the ULN. 16. The patient has a life expectancy > 3 months. 17. The patient is male and at least 18 years of age. 18. The patient agrees to use contraceptives while on study if sexually active. 19. The patient has provided signed informed consent. Exclusion Criteria: 1. The patient has any active malignancy (other than adequately treated nonmelanomatous skin cancer or other noninvasive or in situ neoplasms) and there has been no evidence of disease recurrence during the prior 3 years. 2. The patient has received more than one prior cytotoxic chemotherapy regimen for metastatic disease. (Patients who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.) 3. The patient has received prior therapy with mitoxantrone for advanced prostate cancer (prior adjuvant therapy with mitoxantrone is permitted). 4. The patient has a history of symptomatic congestive heart failure or has a pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) that is ≥ 10% below the LLN. 5. The patient has a history of prior treatment with other agents that directly inhibit IGF, IGFRs, VEGF, or VEGFRs. 6. The patient has known allergy to any of the treatment components. 7. The patient has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or IMC-1121B. 8. The patient is receiving corticosteroids (dexamethasone, prednisone, or others) at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Patients receiving corticosteroids at higher doses may be eligible if their corticosteroid therapy is tapered to study levels (prednisone 5 mg PO BID) prior to first dose of study medication, without concomitant clinical deterioration. 9. The patient has received prior strontium-89, rhenium-186, rhenium-188, or samarium-153 radionucleotide therapy. Patients who have received standard dose radiation to the pelvis for prostate cancer and/or additional external beam radiotherapy to metastatic sites are eligible. 10. The patient has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia (well controlled atrial fibrillation is permitted), psychiatric illness/social situations, active bleeding or pathological condition that carries a high risk of bleeding (eg, tumor involving major vessels, tumor invading to rectal lumen, or known varices), or any other serious uncontrolled medical disorders in the opinion of the investigator. 11. The patient has known or suspected brain or leptomeningeal metastases. 12. The patient has uncontrolled or poorly controlled hypertension. 13. The patient has poorly controlled diabetes mellitus. Patients with a history of diabetes are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition. 14. The patient has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness. Trial Lead Organizations/Sponsors ImClone Systems, Incorporated
Trial Sites
Link to the current ClinicalTrials.gov record. Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain
the same text. Minor
changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and
contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should
be directed to ClinicalTrials.gov. Back to Top |
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