Study With IMC-A12 (Cixutumumab) in Patients Who Have Not Previously Been Treated With Chemotherapy With Metastatic Prostate Cancer

NCT00520481 | Completed Phase 2 Results

• 3 other identifiers: 13934CP13-0603I5A-IE-JAEJ
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 3

Brief Summary

This single arm, multicenter, open-label, Phase II study will enroll chemotherapy-naive participants with metastatic, histologically-confirmed adenocarcinoma of the prostate (stage M1 D2). Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Non-surgically castrated participants must continue the use of luteinizing hormone-releasing hormone (LHRH) agonists during protocol treatment.

Conditions

Adenocarcinoma of the Prostate

Keywords

prostate cancer

Outcome Measures

Primary Outcomes (3)

• Composite Time to Disease Progression (cTTP) for Participants Treated With Cixutumumab

  cTTP was the time from the first day of treatment to the earliest onset of 1 of the following: tumor progression by Response Evaluation Criteria In Solid Tumors \[RECIST, version 1.0\] criteria: unequivocal evidence of progression by bone scan, new skeletal events, symptomatic progression (for participants without measurable disease), or other clinical events attributable to prostate cancer that in the opinion of the investigator require major interventions. Participants without tumor progression at data cut-off were censored.

  From first dose of study drug until progressive disease (Up to 49.2 months)

• Area Under the Curve (AUC) of IMC-A12 Administered at a Dose of 20 mg/kg Every 3 Weeks

  Up to 42 months (predose, 1, 168, 336 and 504 h postdose for Cycles 1 to 4; additionally 24, 72 or 96 h, 120 and 240 or 246 h postdose for Cycle 4; predose and 1 h post dose for Cycles 5 to 9)

• Maximum Concentration (Cmax) of IMC-A12 Administered at a Dose of 20 mg/kg Every 3 Weeks

  Up to 42 months (predose, 1, 168, 336 and 504 h postdose for Cycles 1 to 4; additionally 24, 72 or 96 h, 120 and 240 or 246 h post dose for Cycle 4; predose and 1 h postdose for Cycles 5 to 9)

Secondary Outcomes (7)

• Number of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs)

  From randomization up to 49.2 months (and 30 day follow-up)

• Time to Radiographically Evident Disease Progression

  From first dose of study drug until radiographic progression (up to 48.6 months)

• Number of Participants With Complete Response (CR) or Partial Response (PR) (Tumor Response Rate)

  From Randomization up to progressive disease (49.2 months)

• Percentage of Participants With Prostate Specific Antigen (PSA) Response Rate

  From Randomization up to 6.21 months

• Progression-Free Survival (PFS) Rate at 6 Months

  From randomization up to 48.6 months

Study Arms (1)

IMC-A12

EXPERIMENTAL

Thirty-one participants will receive IMC-A12 at 10 milligrams per kilogram (mg/kg) administered over 1 hour every other week (every 14 days). An additional 10 participants will receive IMC-A12 at a dose of 20 mg/kg every three weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Radiographic evaluation of response will be performed every 8 weeks for the participants treated with intravenous (i.v.) IMC-A12 at 10 mg/kg and every 9 weeks for the participants treated with i.v. IMC-A12 at 20 mg/kg.

Drug: IMC-A12 (Cixutumumab)

Interventions

IMC-A12 (Cixutumumab) DRUG

10 mg/kg i.v. infusion over 1 hour every 2 weeks or 20 mg/kg i.v. infusion over 1 hour every 3 weeks.

Also known as: Cixutumumab, LY3012217

IMC-A12

Eligibility Criteria

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

You may qualify if:

• The participant is male and at least 18 years of age
• The participant has histologically-confirmed adenocarcinoma of the prostate
• The participant has radiographic evidence of metastatic prostate cancer (stage M1 \[D2\])
• The participant has prostate cancer unresponsive or refractory to hormone therapy
• The participant must have evidence of progressive disease defined as at least one of the following:
• a. Progressive measurable disease: using conventional solid tumor criteria.
• b. Bone scan progression: at least one new lesion on bone scan.
• c. Increasing prostate specific antigen (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 nanograms/milliliter (ng/mL)
• The participant has not received prior chemotherapy for metastatic prostate cancer
• The participant had prior surgical or medical castration with a serum testosterone level of \< 50 ng/mL. If the method of castration is LHRH agonists, the participant must be willing to continue the use of LHRH agonists during protocol treatment
• All clinically significant toxic effects (excluding alopecia) of prior surgery, radiotherapy, or hormonal therapy have resolved to grade ≤ 1 based on National Cancer Institute - Common Terminology Criteria for Adverse Events, (NCI-CTCAE)Version 3.0
• The participant has not received antiandrogen therapy for at least 6 weeks (4 weeks for flutamide) prior to study entry and is without evidence of an antiandrogen withdrawal response. For participants whose progression is documented solely by PSA increase, the most recent PSA value enabling study entry must be drawn after the required antiandrogen washout period
• The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1
• The participant has adequate organ function including: absolute neutrophil count ≥ 1500/microliter (μL); platelets ≥ 100,000/μL; hemoglobin ≥ 9.0 grams per deciliter (g/dL); bilirubin ≤ 1.5 times the institutional upper limit of normal (ULN); aspartate transaminase (AST) / alanine transaminase (ALT) ≤ 3 times ULN (\< 5x ULN if liver metastases are present); creatinine ≤ 1.5 x ULN (or calculated creatinine clearance \> 60 milliliter/minute (mL/min); and urine protein ≤ 1+ (if urine protein is ≥ 2+, a 24-hour urine collection must demonstrate \< 1000 mg of protein in 24 hours to allow participation in the study)

You may not qualify if:

• The participant has any active malignancy (other than adequately treated nonmelanomatous skin cancer or other noninvasive or in situ neoplasms), or has an adequately-treated prior cancer but has been disease free for \< 3 years
• The participant has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia (well-controlled atrial fibrillation is permitted), psychiatric illness/social situations, active bleeding or pathological condition that carries a high risk of bleeding (eg, tumor involving major vessels, tumor invading to rectal lumen, or known varices), or any other serious uncontrolled medical disorder in the opinion of the investigator
• The participant has a known hypersensitivity to therapeutic protein products
• The participant has known or suspected brain or leptomeningeal metastases
• The participant has received radiotherapy ≤ 21 days prior to first dose of IMC-A12
• The participant has received prior radiation therapy to \> 30% of the bone marrow or prior strontium-89, rhenium-186, rhenium-188, or samarium-153 (participants who have received standard dose radiation to the pelvis for prostate cancer and no additional radiotherapy are eligible)
• The participant has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
• The participant has received more than one course of radiotherapy to a single site of metastatic bony disease
• The participant has a bone scan that indicates "superscan" (that is (ie), extensive metastasis to bone in numerous areas, too numerous to count or define)
• The participant is receiving corticosteroids (dexamethasone, prednisone, or others) for anorexia, weight loss, analgesia or other cancer-related symptoms(Corticosteroids may not be instituted once a participant has begun therapy on-study
• The participant requires ongoing, regularly scheduled opiate analgesic therapy for cancer related pain. Intermittent, infrequent low-potency opiate-use (example, oxycodone, codeine) is permitted
• The participant has a history of prior treatment with other agents that specifically target the insulin-like growth factor (IGF) receptor

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (3)

ImClone Investigational Site

San Francisco, California, 94115, United States

Location

ImClone Investigational Site

Portland, Oregon, 97239, United States

Location

ImClone Investigational Site

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cixutumumab

Condition Hierarchy (Ancestors)

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

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2007
• First Posted: August 24, 2007
• Study Start: August 1, 2007
• Primary Completion: January 1, 2012
• Study Completion: August 1, 2013
• Last Updated: July 19, 2018
• Results First Posted: July 19, 2018

Record last verified: 2018-06

Locations

US (3)