SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial
- Conditions
- CancerColon CancerColorectal CancerMetastatic CancerRectal CancerMetastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT00418938
- Lead Sponsor
- Amgen
- Brief Summary
This is a multi-center, open-label, randomized, phase 2, two-arm clinical trial to be conducted in the United States. Approximately 210 eligible KRAS wild-type expressing metastatic colorectal cancer subjects who have failed first-line oxaliplatin-based chemotherapy (with at least 4 doses of oxaliplatin-based chemotherapy) with at least 4 doses of bevacizumab (failure is defined as toxicity due to oxaliplatin-based chemotherapy or progression of disease on first-line treatment) will be randomized in a 1:1 ratio to receive either a once-every-two-weeks (Q2W) FOLFIRI regimen plus panitumumab 6 mg/kg or a Q2W FOLFIRI regimen plus bevacizumab (either 5 mg/kg or 10 mg/kg, depending on physician choice and institutional standard of care).
- Detailed Description
This phase 2, multicenter, open-label, randomized, two-arm study was designed to estimate the treatment effect of panitumumab in combination with FOLFIRI compared to bevacizumab in combination with FOLFIRI in subjects with metastatic colorectal cancer (mCRC) who had failed first-line therapy with at least 4 doses of oxaliplatin-based chemotherapy and bevacizumab. After data became available demonstrating that the treatment effect of antiepidermal growth factor receptor (EGFR) agents was limited to patients with wild-type Kirsten rat Sarcoma-2 virus (KRAS) mCRC, the study was amended to enroll only subjects with wild-type KRAS tumors. Eligible subjects were randomized in a 1:1 ratio to receive panitumumab 6 mg/kg plus FOLFIRI once every 2 weeks (Q2W) or bevacizumab 5 mg/kg or 10 mg/kg plus FOLFIRI Q2W. Randomization was stratified by the reason for first-line treatment failure (progression vs toxicity) and by intended bevacizumab dose (5 mg/kg vs 10 mg/kg). The intended bevacizumab doses were ascertained from sites at the time of site initiation. Subjects were treated with all or any components of second-line treatment until the occurrence of unacceptable adverse events, disease progression, death, loss to follow up, or study withdrawal by the subject, investigator, or sponsor. Tumor response was evaluated by blinded central radiology review per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 and by the investigator using either modified RECIST version 1.0 or clinical assessment. After subjects permanently discontinued all components of second-line treatment, they were to undergo a safety follow-up assessment 30 (± 7) days after the last dose. Subjects ending second-line treatment before disease progression were followed for PFS (radiographic disease assessment) every 12 weeks (± 14 days) from the safety follow-up visit until disease progression, initiation of a new therapy for mCRC, or until approximately 100 PFS events were observed in subjects with wild-type KRAS tumors. Subjects were also followed for survival every 12 weeks (± 14 days) from the safety follow-up assessment until approximately 100 PFS events were observed in subjects with wild-type KRAS tumors.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 266
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B Bevacizumab FOLFIRI + Bevacizumab Arm B Leucovorin FOLFIRI + Bevacizumab Arm A 5-Fluorouracil FOLFIRI + Panitumumab Arm A Irinotecan FOLFIRI + Panitumumab Arm B Irinotecan FOLFIRI + Bevacizumab Arm B 5-Fluorouracil FOLFIRI + Bevacizumab Arm A Panitumumab FOLFIRI + Panitumumab Arm A Leucovorin FOLFIRI + Panitumumab
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) From randomization up to 65 months. Progression-free survival is defined as time from the date of randomization to the date of first progression per modified RECIST version 1.0 (based on central review of the radiographic scans), or death within 60 days after the last evaluable tumor assessment or randomization date (whichever is later).
- Secondary Outcome Measures
Name Time Method Overall Survival From randomization up to 65 months. Overall survival is defined as time from the date of randomization to the date of death due to any cause. Subjects who have not died or are lost to follow-up at the analysis cutoff date will be censored at their last contact date.
Time to Progression From randomization up to 65 months. Time to progression is defined as time from the date of randomization to the date of radiographic disease progression per modified RECIST version 1.0 (per central assessment).
Objective Response Rate From randomization up to 65 months. Objective response rate is defined as incidence of either a confirmed complete response (CR) or partial response (PR) on study up to starting a new anti-tumor therapy and will be based on modified RECIST version 1.0 (responder) by central assessment.
Time to Response From randomization up to 65 months. Time to response is defined as time from the date of randomization to the date of first confirmed objective response
Disease Control From randomization up to 65 months. Disease control is defined as incidence of objective response or stable disease on study up to starting a new anti-tumor therapy.
Duration of Response From randomization up to 65 months. Duration of response is defined as time from first confirmed objective response to disease progression per modified RECIST version 1.0 (by central assessment).