Neoplasms

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Digestive System Diseases

Neoplasm Metastasis

Colorectal Neoplasms

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Digestive System Neoplasms

Gastrointestinal Diseases

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Antineoplastic Agents

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Micronutrients

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Irinotecan

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Fluorouracil

Panitumumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

400mg/m\^2 bolus IV (in the vein) over 2-4 min, followed by 2400mg/m\^2 continuous IV over 46 hours for the first 2 cycles, increased to 3000mg/m\^2 thereafter if no significant side effects

5-Fluorouracil

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).

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.

SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial

A Multi-center, Open-label, Randomized, Phase 2 Clinical Trial Evaluating Safety and Efficacy of FOLFIRI With Either Panitumumab or Bevacizumab as Second-Line Treatment in Subjects With Metastatic Colorectal Cancer With Wild-type KRAS Tumors

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).

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.

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 is defined as time from the date of randomization to the date of first confirmed objective response

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).

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 is defined as time from first confirmed objective response to disease progression per modified RECIST version 1.0 (by central assessment).

Amgen

The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.

subjects in this arm receive once-every-2-weeks (Q2W) FOLFIRI regimen plus panitumumab 6 mg/kg

Panitumumab Plus FOLFIRI

subjects in this arm receive once-every-2-weeks (Q2W) FOLFIRI regimen plus bevacizumab (either 5 mg/kg or 10 mg/kg, depending on physician choice and institutional standard of care)

Bevacizumab Plus FOLFIRI

Total

Age, Continuous

Sex: Female, Male

White or Caucasian

Black or African American

Hispanic or Latino

Asian

American Indian or Alaska Native

Other

Race/Ethnicity, Customized

0 (Fully active)

1 (Restricted in physically strenuous activity)

Missing

Scale range from 0 (fully active) to 5(dead), only status 0 or 1 is included by protocol.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Colon

Rectum

Primary tumor diagnosis

Number of metastatic organs

Study Director

Wild-type KRAS (n=91,91)

Mutant KRAS (n=36,32)

Analysis population include all enrolled subjects who received at least one dose of study therapy and do not include subjects with unevaluable KRAS status.

Progression-free Survival (PFS)

Overall Survival

Analysis population include all enrolled subjects who received at least one dose of study therapy, who had at least one baseline uni-dimensionally measurable target lesion based on central (and investigator, respectively) assessment using a modified RECIST criteria version 1.0, and who had evaluable KRAS status.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial	NCT00418938	Cancer Colon Cancer Colorectal Canc... Metastatic Canc... Rectal Cancer Metastatic Colo...	Panitumumab Bevacizumab Leucovorin Irinotecan 5-Fluorouracil	18 Years -	Amgen
SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial	NCT00418938	Cancer Colon Cancer Colorectal Canc... Metastatic Canc... Rectal Cancer Metastatic Colo...	Panitumumab Bevacizumab Leucovorin Irinotecan 5-Fluorouracil	18 Years -	Amgen
SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial	NCT00418938	Cancer Colon Cancer Colorectal Canc... Metastatic Canc... Rectal Cancer Metastatic Colo...	Panitumumab Bevacizumab Leucovorin Irinotecan 5-Fluorouracil	18 Years -	Amgen

Spots Global Cancer Trial Database for 2nd line mcrc therapy