Clinical trial NCT00520481: Study With IMC-A12 (Cixutumumab) in Patients Who Have Not Previously Been Treated With Chemotherapy With Metastatic Prostate Cancer
Official title: Phase 2 Single Arm, Open-Label Study of IMC-A12 in Asymptomatic, Chemotherapy-Naïve Patients With Metastatic Androgen-Independent Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma of the Prostate
Keywords: prostate cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2007-08-24
Enrollment: 41
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Thirty-one chemotherapy-naїve participants with asymptomatic metastatic androgen-independent prostate cancer will be enrolled and treated with intravenous (i.v.) IMC-A12 (Cixutumumab) at 10 milligrams per kilogram (mg/kg) administered over 1 hour every 2 weeks. An additional 10 participants will be enrolled and treated with IMC-A12 at a dose of 20 mg/kg every three weeks. Treatment will continue until evidence of disease progression or intolerable toxicity. Radiographic evaluation of response will be performed every 8 weeks for the participants treated with i.v. IMC-A12 at 20 mg/kg.

Eligibility criteria: Inclusion Criteria

* 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)
* The participant has fasting serum glucose \< 120 milligrams per deciliter (mg/dL) or below the ULN
* The participant has adequate coagulation function as defined by an international normalized ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 1.5 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 is asymptomatic from prostate cancer. Participants with minimal, infrequent cancer-related symptoms are eligible. Criteria regarding pain and analgesic use are detailed below
* The participant has a life expectancy \> 6 months
* The participant, if sexually active, agrees to use contraceptives while on study
* The participant has provided signed informed consent

Exclusion Criteria

* 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

Primary outcomes:
measure: Composite Time to Disease Progression (cTTP) for Participants Treated With Cixutumumab
timeFrame: From first dose of study drug until progressive disease (Up to 49.2 months)
measure: Area Under the Curve (AUC) of IMC-A12 Administered at a Dose of 20 mg/kg Every 3 Weeks
timeFrame: 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)
measure: Maximum Concentration (Cmax) of IMC-A12 Administered at a Dose of 20 mg/kg Every 3 Weeks
timeFrame: 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:
measure: Number of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs)
timeFrame: From randomization up to 49.2 months (and 30 day follow-up)
measure: Time to Radiographically Evident Disease Progression
timeFrame: From first dose of study drug until radiographic progression (up to 48.6 months)
measure: Number of Participants With Complete Response (CR) or Partial Response (PR) (Tumor Response Rate)
timeFrame: From Randomization up to progressive disease (49.2 months)
measure: Percentage of Participants With Prostate Specific Antigen (PSA) Response Rate
timeFrame: From Randomization up to 6.21 months
measure: Progression-Free Survival (PFS) Rate at 6 Months
timeFrame: From randomization up to 48.6 months
measure: Area Under the Curve (AUC) of IMC-A12 Administered at a Dose of 10 mg/kg Every 2 Weeks
timeFrame: Up to 42 months (predose and 1 h postdose for Cycles 1, 5, 9, 13, 17 and 21; additionally immediately following dosing, 168 and 336 h postdose for Cycle 1 only)
measure: Maximum Concentration (Cmax) of IMC-A12 Administered at a Dose of 10 mg/kg Every 2 Weeks
timeFrame: Up to 42 months (predose and 1 h postdose for Cycles 1, 5, 9, 13, 17 and 21; additionally immediately following dosing, 168 and 336 h postdose for Cycle 1 only)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: ImClone Investigational Site
state: California
city: Portland
country: United States
facility: ImClone Investigational Site
state: Oregon
city: Seattle
country: United States
facility: ImClone Investigational Site
state: Washington
Study officials:
affiliation: Eli Lilly and Company
name: 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
References: