A Study of IMC-A12 or Ramucirumab Plus Mitoxantrone and Prednisone in Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: IMC-A12; Mitoxantrone; Prednisone; IMC-1121B (ramucirumab)
Intervention description: IMC-A12 is to be administered as an I.V. infusion, 6 mg/kg over 1 hour on Days 1, 8, and 15 of each 3-week (21-day) cycle. IMC-A12 treatment is to continue until there is evidence of disease progression, death, intolerable toxicity, or other withdrawal criteria are met.; Mitoxantrone is to be administered as an I.V. infusion, at 12 milligrams/square meter (mg/m^2) over 5-15 minutes on Day 1 during a 3-week (21-day) cycle. Mitoxantrone treatment is to be continued for a maximum of 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤ 144 mg/m^2) or until there is evidence of disease progression, death, or intolerable toxicity.; Prednisone (5 mg) is to be self-administered PO BID, each day of the 21-day cycle.; IMC-1121B (ramucirumab) is to be administered as an intravenous (IV) infusion, 6 milligrams/kilogram (mg/kg) over 1 hour on Days 1, 8, and 15 of each 3-week (21-day) cycle. Ramucirumab treatment is to continue until there is evidence of disease progression, death, intolerable toxicity, or other withdrawal criteria are met.
Intervention MeSH terms: Prednisone; Mitoxantrone; Ramucirumab; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 138.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate Cancer

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).
    

Eligibility 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