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

NCT ID: NCT00683475

Last Updated: 2014-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2011-09-30

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 (APIC).

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 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 Hormone Refractory Prostate Cancer (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 Insulin Like Growth Factor Receptor (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 (ramucirumab) in combination with mitoxantrone and prednisone in participants with AIPC.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone

Group Type: EXPERIMENTAL

Mitoxantrone

Intervention Type: DRUG

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

Intervention Type: DRUG

Prednisone (5 mg) is to be self-administered PO BID, each day of the 21-day cycle.

IMC-1121B (ramucirumab)

Intervention Type: BIOLOGICAL

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.

IMC-A12 + Mitoxantrone + Prednisone

Group Type: EXPERIMENTAL

IMC-A12

Intervention Type: BIOLOGICAL

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Prednisone (5 mg) is to be self-administered PO BID, each day of the 21-day cycle.

Interventions

IMC-A12

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.

Intervention Type: BIOLOGICAL

Mitoxantrone

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.

Intervention Type: DRUG

Prednisone

Prednisone (5 mg) is to be self-administered PO BID, each day of the 21-day cycle.

Intervention Type: DRUG

IMC-1121B (ramucirumab)

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 Type: BIOLOGICAL

Other Intervention Names

cixutumumab; LY3012217; ramucirumab; IMC-1121B; LY3009806

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

• 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 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

ImClone Investigational Site

La Jolla, California, United States

ImClone Investigational Site

New Haven, Connecticut, United States

ImClone Investigational Site

Boca Raton, Florida, United States

ImClone Investigational Site

Port Saint Lucie, Florida, United States

ImClone Investigational Site

Atlanta, Georgia, United States

ImClone Investigational Site

Chicago, Illinois, United States

ImClone Investigational Site

Chlcago, Illinois, United States

ImClone Investigational Site

Evanston, Illinois, United States

ImClone Investigational Site

Maryville, Illinois, United States

ImClone Investigational Site

Cedar Rapids, Iowa, United States

ImClone Investigational Site

Metairie, Louisiana, United States

ImClone Investigational Site

Ann Arbor, Michigan, United States

ImClone Investigational Site

Rochester, Minnesota, United States

ImClone Investigational Site

St Louis, Missouri, United States

ImClone Investigational Site

Billings, Montana, United States

ImClone Investigational Site

Roseland, New Jersey, United States

ImClone Investigational Site

Buffalo, New York, United States

ImClone Investigational Site

East Setauket, New York, United States

ImClone Investigational Site

New York, New York, United States

ImClone Investigational Site

New York, New York, United States

ImClone Investigational Site

New York, New York, United States

ImClone Investigational Site

New York, New York, United States

ImClone Investigational Site

Durham, North Carolina, United States

ImClone Investigational Site

Cleveland, Ohio, United States

ImClone Investigational Site

Philadelphia, Pennsylvania, United States

ImClone Investigational Site

Pittsburgh, Pennsylvania, United States

ImClone Investigational Site

Greenville, South Carolina, United States

ImClone Investigational Site

Knoxville, Tennessee, United States

ImClone Investigational Site

Nashville, Tennessee, United States

ImClone Investigational Site

Abilene, Texas, United States

ImClone Investigational Site

Dallas, Texas, United States

ImClone Investigational Site

Houston, Texas, United States

ImClone Investigational Site

Houston, Texas, United States

ImClone Investigational Site

Seattle, Washington, United States

ImClone Investigational Site

Seattle, Washington, United States

ImClone Investigational Site

Madison, Wisconsin, United States

Countries

United States

References

Hussain M, Rathkopf D, Liu G, Armstrong A, Kelly WK, Ferrari A, Hainsworth J, Joshi A, Hozak RR, Yang L, Schwartz JD, Higano CS. A randomised non-comparative phase II trial of cixutumumab (IMC-A12) or ramucirumab (IMC-1121B) plus mitoxantrone and prednisone in men with metastatic docetaxel-pretreated castration-resistant prostate cancer. Eur J Cancer. 2015 Sep;51(13):1714-24. doi: 10.1016/j.ejca.2015.05.019. Epub 2015 Jun 13.

Reference Type: DERIVED

PMID: 26082390 (View on PubMed)

Other Identifiers

CP18-0601

Identifier Type: OTHER

Identifier Source: secondary_id

I4T-IE-JVBS

Identifier Type: OTHER

Identifier Source: secondary_id

13924

Identifier Type: -

Identifier Source: org_study_id