Status:

COMPLETED

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

Lead Sponsor:

Eli Lilly and Company

Conditions:

Prostate Cancer

Eligibility:

MALE

18+ years

Phase:

PHASE2

Brief 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 ...

Detailed Description

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 combinatio...

Eligibility Criteria

Inclusion

  • 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;
  • Progressive measurable disease: using conventional solid tumor criteria
  • Bone scan progression: at least two new lesions on bone scan
  • 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

  • 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;
  • Progressive measurable disease: using conventional solid tumor criteria
  • Bone scan progression: at least two new lesions on bone scan
  • 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

Key Trial Info

Start Date :

August 1 2008

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

September 1 2011

Estimated Enrollment :

138 Patients enrolled

Trial Details

Trial ID

NCT00683475

Start Date

August 1 2008

End Date

September 1 2011

Last Update

October 16 2014

Active Locations (36)

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Page 1 of 9 (36 locations)

1

ImClone Investigational Site

La Jolla, California, United States, 92093

2

ImClone Investigational Site

New Haven, Connecticut, United States, 06520

3

ImClone Investigational Site

Boca Raton, Florida, United States, 33486

4

ImClone Investigational Site

Port Saint Lucie, Florida, United States, 34952