A Study of IMC-A12 or Ramucirumab Plus Mitoxantrone and Prednisone in Prostate Cancer

• Status: Completed
• Trial end date: 2011-09-01
• Target enrollment: 0
• Participant gender: Male

Summary

The purpose of this study is to determine whether IMC-A12 or IMC-1121B (ramucirumab) with Mitoxantrone and Prednisone is effective in the treatment of metastatic androgen- independent prostate cancer (APIC).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eli Lilly and Company
• Treatments: Antibodies, Monoclonal; Mitoxantrone; Prednisone; Ramucirumab

Criteria

Inclusion Criteria:

• The participant has histologically-confirmed adenocarcinoma of the prostate

• The participant has radiographic evidence of metastatic prostate cancer (stage M1 or D2)

• The participant has prostate cancer unresponsive or refractory to hormone therapy (androgen-independent)

• The participant 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

• The participant must have evidence of progressive disease defined as at least one of the following;

1. Progressive measurable disease: using conventional solid tumor criteria

2. Bone scan progression: at least two new lesions on bone scan

3. 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

• The participant has a PSA ≥ 2 ng/mL

• The participant 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 participant must be willing to continue the use of LHRH agonists during protocol treatment

• The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2

• The participant has adequate hematologic function (absolute neutrophil count [ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)

• The participant 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)

• The participant has adequate renal function (creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 40 mL/min)

• The participant'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

• The participant 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]). Participants 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)

• The participant has a fasting serum glucose level of < 160 mg/dL, or below the ULN

Exclusion Criteria:

• The participant has received more than one prior cytotoxic chemotherapy regimen for metastatic disease. (Participants who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.)

• The participant has received prior therapy with mitoxantrone for advanced prostate cancer (prior adjuvant therapy with mitoxantrone is permitted)

• The participant 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

• The participant has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or Ramucirumab

• The participant is receiving corticosteroids (dexamethasone, prednisone, or others) at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Participants 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

• The participant has known or suspected brain or leptomeningeal metastases

• The participant has uncontrolled or poorly controlled hypertension

• The participant has poorly controlled diabetes mellitus. Inclusion Criteria:

• The participant has histologically-confirmed adenocarcinoma of the prostate

• The participant has radiographic evidence of metastatic prostate cancer (stage M1 or D2)

• The participant has prostate cancer unresponsive or refractory to hormone therapy (androgen-independent)

• The participant 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

• The participant must have evidence of progressive disease defined as at least one of the following;

1. Progressive measurable disease: using conventional solid tumor criteria

2. Bone scan progression: at least two new lesions on bone scan

3. 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

• The participant has a PSA ≥ 2 ng/mL

• The participant 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 participant must be willing to continue the use of LHRH agonists during protocol treatment

• The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2

• The participant has adequate hematologic function (absolute neutrophil count [ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)

• The participant 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)

• The participant has adequate renal function (creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 40 mL/min)

• The participant'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

• The participant 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]). Participants 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)

• The participant has a fasting serum glucose level of < 160 mg/dL, or below the ULN

Exclusion Criteria:

• The participant has received more than one prior cytotoxic chemotherapy regimen for metastatic disease. (Participants who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.)

• The participant has received prior therapy with mitoxantrone for advanced prostate cancer (prior adjuvant therapy with mitoxantrone is permitted)

• The participant 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

• The participant has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or Ramucirumab

• The participant is receiving corticosteroids (dexamethasone, prednisone, or others) at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Participants 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

• The participant has known or suspected brain or leptomeningeal metastases

• The participant has uncontrolled or poorly controlled hypertension

• The participant has poorly controlled diabetes mellitus. Participants 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

• The participant has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness 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

• The participant has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness