Clinical trial NCT00411450: Panitumumab Regimen Evaluation in Colorectal Cancer to Estimate Primary Response to Treatment
Official title: Multi Center, Open Label, Single Arm Trial Evaluating Panitumumab in Combination With FOLFIRI Therapy Following First Line FOLFOX and Bevacizumab Treatment of Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colon Cancer
Colorectal Cancer
Rectal Cancer
Cancer
Metastatic Cancer
Metastatic Colorectal Cancer
Oncology
Keywords: k-ras
biomarker
colorectal
colon
rectal
FOLFOX
FOLFIRI
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2006-12-14
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective is to estimate the effect of the human homolog of the Kirsten rat sarcoma-2 virus oncogene (KRAS) mutation status (wild type versus mutant) from tumor tissue on efficacy endpoints in patients with metastatic colorectal cancer (mCRC) receiving second-line chemotherapy with panitumumab after failing first-line treatment.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of metastatic adenocarcinoma of the colon or rectum
* Available paraffin-embedded tumor tissue
* Failure of first line treatment containing fluoropyrimidine and oxaliplatin based chemotherapy with bevacizumab for mCRC
* Measurable disease
* Adequate hematologic, renal, hepatic and metabolic function

Exclusion Criteria:

* Radiotherapy ≤ 2 weeks prior to Day 1 of Cycle 1
* Unresolved toxicity(ies) from prior anti cancer therapy that, in the opinion of the investigator, precludes the subject from study enrollment
* Prior irinotecan therapy, anti epidermal growth factor receptor (EGFr) therapy, or vaccine for the treatment of mCRC
* CYP3A4 enzyme inducers, inhibitors, and substrates (eg, phenytoin, phenobarbital, carbamazepine, ketoconazole, rifampin, rifabutin, and St. John's Wort) ≤ 2 weeks prior to Day 1 of Cycle 1
* Infection requiring systemic anti infectives completed ≤ 2 weeks prior to Day 1 of Cycle 1
* Clinically significant cardiovascular disease
* History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis)
* Pulmonary embolism, deep vein thrombosis, or other significant thromboembolic event ≤ 8 weeks prior to Day 1 of Cycle 1
* Any significant bleeding ≤ 6 weeks prior to Day 1 of Cycle 1, per the investigator's judgement
* Gastroduodenal ulcer(s) determined by endoscopy to be active or uncontrolled gastrointestinal ulcer ≤ 4 weeks prior to Day1 of Cycle 1
* Any co-morbid disease or condition that could increase the risk of toxicity (eg, dihydropyrimidine deficiency, significant ascites, or pleural effusion)
* Major surgery (requiring general anesthesia), open biopsy, or significant traumatic injury ≤ 4 weeks prior to Day1 of Cycle 1. Subjects must have recovered from surgery and have no significant complications

Primary outcomes:
measure: Objective Response Rate at Weeks 17 and 25
timeFrame: Week 17 and Week 25
measure: Best Response During Second-Line Treatment
timeFrame: Tumor response was assessed at Weeks 9, 17, 25, and 33, and once every 12 weeks thereafter until the end of second-line treatment; maximum time on treatment was 77 weeks.
measure: Progression-free Survival Rate at Weeks 17 and 25
timeFrame: Week 17 and Week 25
measure: Progression-free Survival Time
timeFrame: From Study Day 1 until the data cut-off date of 2 January 2009; median follow-up time was 39 weeks, with a maximum of 93 weeks.
measure: Disease Control Rate at Weeks 17 and 25
timeFrame: Week 17 and Week 25
measure: Duration of Response
timeFrame: Tumor response was assessed at Weeks 9, 17, 25, and 33, and once every 12 weeks thereafter until the end of second-line treatment; maximum time on treatment was 77 weeks.
measure: Overall Survival
timeFrame: From Study Day 1 until the data cut-off date of 2 January 2009; median follow-up time was 39 weeks, with a maximum of 93 weeks.
measure: Time to Treatment Failure
timeFrame: Tumor response was assessed at Weeks 9, 17, 25, and 33, and once every 12 weeks thereafter until the end of second-line treatment; maximum time on treatment was 77 weeks.
measure: Time to Progression
timeFrame: From Study Day 1 until the data cut-off date of 2 January 2009; median follow-up time was 39 weeks, with a maximum of 93 weeks.
measure: Time to Response
timeFrame: Tumor response was assessed at Weeks 9, 17, 25, and 33, and once every 12 weeks thereafter until the end of second-line treatment; maximum time on treatment was 77 weeks.
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From the first dose date to 30 days after the last dose date. The median time frame is 4.5 months.
measure: Number of Participants With Grade 4 Laboratory Toxicities
timeFrame: From the first dose date to 30 days after the last dose date. The median time frame is 4.5 months.
measure: Number of Participants Who Developed Antibodies to Panitumumab
timeFrame: Prior to first dose and 28 days after the last dose of second-line treatment
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Cohn AL, Shumaker GC, Khandelwal P, Smith DA, Neubauer MA, Mehta N, Richards D, Watkins DL, Zhang K, Yassine MR. An open-label, single-arm, phase 2 trial of panitumumab plus FOLFIRI as second-line therapy in patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2011 Sep;10(3):171-7. doi: 10.1016/j.clcc.2011.03.022. Epub 2011 Apr 28.
citation: Weeraratne D, Chen A, Pennucci JJ, Wu CY, Zhang K, Wright J, Perez-Ruixo JJ, Yang BB, Kaliyaperumal A, Gupta S, Swanson SJ, Chirmule N, Starcevic M. Immunogenicity of panitumumab in combination chemotherapy clinical trials. BMC Clin Pharmacol. 2011 Nov 9;11:17. doi: 10.1186/1472-6904-11-17.