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

NCT00683475 | Completed Phase 2 Results DMC

• 3 other identifiers: 13924CP18-0601I4T-IE-JVBS
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 36

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).

Conditions

Prostate Cancer

Keywords

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Composite Progression-free Survival (cPFS)

  Defined as the median time from randomization to the earliest of: 1. Tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST); 2. Evidence of progression by bone scan, performed after completion of the first 3 cycles, demonstrating the appearance of \>=2 new lesions; 3. New skeletal events (New pathologic bone fracture in the region of metastatic disease; New bone lesion requiring radiation or surgery; Spinal cord or nerve root compression) 4. Symptomatic progression (for participants without measurable disease); 5. Other clinical events attributable to prostate cancer that require major interventions; or 6. Death from any cause Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.

  Randomization to composite progressive disease, up to 23.4 months

Secondary Outcomes (16)

• Summary Listing of Participants Reporting Treatment-Emergent Adverse Events

  Randomization to 36.3 months

• Time to Radiographic Evidence of Disease Progression

  Randomization to date of radiographic progression, up to 36.3 months

• Prostate Specific Antigen (PSA) Response Rate

  Baseline up to data cut-off date (up to 36.3 months)

• Composite Progression-free Survival (cPFS) at 6-months

  6 months

• Composite Progression-free Survival (cPFS) at 9-months

  9 months

Study Arms (2)

IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone

EXPERIMENTAL

Drug: Mitoxantrone; Drug: Prednisone; Biological: IMC-1121B (ramucirumab)

IMC-A12 + Mitoxantrone + Prednisone

EXPERIMENTAL

Biological: IMC-A12; Drug: Mitoxantrone; Drug: Prednisone

Interventions

IMC-A12 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.

Also known as: cixutumumab, LY3012217

IMC-A12 + Mitoxantrone + Prednisone

Mitoxantrone 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.

IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone; IMC-A12 + Mitoxantrone + Prednisone

Prednisone DRUG

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

IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone; IMC-A12 + Mitoxantrone + Prednisone

IMC-1121B (ramucirumab) 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.

Also known as: ramucirumab, IMC-1121B, LY3009806

IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (36)

ImClone Investigational Site

La Jolla, California, 92093, United States

Location

ImClone Investigational Site

New Haven, Connecticut, 06520, United States

Location

ImClone Investigational Site

Boca Raton, Florida, 33486, United States

Location

ImClone Investigational Site

Port Saint Lucie, Florida, 34952, United States

Location

ImClone Investigational Site

Atlanta, Georgia, 30318, United States

Location

ImClone Investigational Site

Chicago, Illinois, 60611, United States

Location

ImClone Investigational Site

Chlcago, Illinois, 60637, United States

Location

ImClone Investigational Site

Evanston, Illinois, 60201, United States

Location

ImClone Investigational Site

Maryville, Illinois, 62062, United States

Location

ImClone Investigational Site

Cedar Rapids, Iowa, 52402, United States

Location

ImClone Investigational Site

Metairie, Louisiana, 70006, United States

Location

ImClone Investigational Site

Ann Arbor, Michigan, 48109, United States

Location

ImClone Investigational Site

Rochester, Minnesota, 55905, United States

Location

ImClone Investigational Site

St Louis, Missouri, 63110, United States

Location

ImClone Investigational Site

Billings, Montana, 59101, United States

Location

ImClone Investigational Site

Roseland, New Jersey, 07068, United States

Location

ImClone Investigational Site

Buffalo, New York, 14263, United States

Location

ImClone Investigational Site

East Setauket, New York, 11733, United States

Location

ImClone Investigational Site

New York, New York, 10016, United States

Location

ImClone Investigational Site

New York, New York, 10019, United States

Location

ImClone Investigational Site

New York, New York, 10021, United States

Location

ImClone Investigational Site

New York, New York, 10032, United States

Location

ImClone Investigational Site

Durham, North Carolina, 27710, United States

Location

ImClone Investigational Site

Cleveland, Ohio, 44195, United States

Location

ImClone Investigational Site

Philadelphia, Pennsylvania, 19111, United States

Location

ImClone Investigational Site

Pittsburgh, Pennsylvania, 15232, United States

Location

ImClone Investigational Site

Greenville, South Carolina, 29605, United States

Location

ImClone Investigational Site

Knoxville, Tennessee, 37920, United States

Location

ImClone Investigational Site

Nashville, Tennessee, 37203, United States

Location

ImClone Investigational Site

Abilene, Texas, 79606, United States

Location

ImClone Investigational Site

Dallas, Texas, 75246, United States

Location

ImClone Investigational Site

Houston, Texas, 77030-4009, United States

Location

ImClone Investigational Site

Houston, Texas, 77030, United States

Location

ImClone Investigational Site

Seattle, Washington, 98104, United States

Location

ImClone Investigational Site

Seattle, Washington, 98109, United States

Location

ImClone Investigational Site

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• 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.

  PMID: 26082390 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cixutumumab; Mitoxantrone; Prednisone; Ramucirumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2008
• First Posted: May 23, 2008
• Study Start: August 1, 2008
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: October 16, 2014
• Results First Posted: June 18, 2014

Record last verified: 2014-10

Locations

US (36)