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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00683475
First received: May 19, 2008
Last updated: August 9, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Biological: IMC-A12
Drug: Mitoxantrone
Drug: Prednisone
Biological: IMC-1121B (ramucirumab)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized Study of IMC-A12 or IMC-1121B Plus Mitoxantrone and Prednisone in Metastatic Androgen-Independent Prostate Cancer (AIPC) Following Disease Progression on Docetaxel-Based Chemotherapy

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 37 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Summary Listing of Participants Reporting Treatment-Emergent Adverse Events [ Time Frame: 37 months ] [ Designated as safety issue: Yes ]
  • Radiographically evidence of disease progression [ Time Frame: 37 months ] [ Designated as safety issue: No ]
  • Prostate specific antigen (PSA) response rate [ Time Frame: 37 months ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) at 6-months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) at 9-months [ Time Frame: 9 months ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) at 12-months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: 37 months ] [ Designated as safety issue: No ]
  • Objective Response Rate (ORR) [ Time Frame: 37 months ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) at study day 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) at study day 15 [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) at study day 16 [ Time Frame: Day 16 ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) at study day 30 [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
  • Minimum concentration (Cmin) at study day 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Minimum concentration (Cmin) at study day 15 [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Minimum concentration (Cmin) at study day 16 [ Time Frame: Day 16 ] [ Designated as safety issue: No ]
  • Minimum concentration (Cmin) at study day 30 [ Time Frame: Day 30 ] [ Designated as safety issue: No ]

Enrollment: 133
Study Start Date: August 2008
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone Drug: Mitoxantrone
Mitoxantrone is to be administered as an I.V. infusion, at 12 mg/m2 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/m2) or until there is evidence of disease progression, death, or intolerable toxicity.
Drug: Prednisone
Prednisone (5 mg) is to be self-administered PO BID,each day of the 21-day cycle.
Biological: IMC-1121B (ramucirumab)
IMC-1121B (ramucirumab) 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. Ramucirumab treatment is to continue until there is evidence of disease progression, death, intolerable toxicity, or other withdrawal criteria are met.
Other Names:
  • ramucirumab
  • IMC-1121B
Experimental: IMC-A12 + Mitoxantrone + Prednisone Biological: 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.
Drug: Mitoxantrone
Mitoxantrone is to be administered as an I.V. infusion, at 12 mg/m2 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/m2) or until there is evidence of disease progression, death, or intolerable toxicity.
Drug: Prednisone
Prednisone (5 mg) is to be self-administered PO BID,each day of the 21-day cycle.

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 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 (ramucirumab) in combination with mitoxantrone and prednisone in patients with AIPC.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient has histologically-confirmed adenocarcinoma of the prostate
  • The patient has radiographic evidence of metastatic prostate cancer (stage M1 or D2)
  • The patient has prostate cancer unresponsive or refractory to hormone therapy (androgen-independent)
  • 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
  • The patient 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 patient has a PSA ≥ 2 ng/mL
  • 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
  • The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2
  • The patient has adequate hematologic function (absolute neutrophil count [ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)
  • 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)
  • The patient has adequate renal function (creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 40 mL/min)
  • 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
  • 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)
  • The patient has a fasting serum glucose level of < 160 mg/dL, or below the ULN

Exclusion Criteria:

  • 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.)
  • The patient has received prior therapy with mitoxantrone for advanced prostate cancer (prior adjuvant therapy with mitoxantrone is permitted)
  • 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
  • The patient has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or Ramucirumab
  • 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
  • The patient has known or suspected brain or leptomeningeal metastases
  • The patient has uncontrolled or poorly controlled hypertension
  • 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
  • The patient has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00683475

  Show 36 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00683475     History of Changes
Other Study ID Numbers: 13924, CP18-0601, I4T-IE-JVBS
Study First Received: May 19, 2008
Last Updated: August 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Mitoxantrone
Prednisone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 20, 2014