SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial
Primary Purpose
Cancer, Colon Cancer, Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Panitumumab
Bevacizumab
Leucovorin
Irinotecan
5-Fluorouracil
Sponsored by
About this trial
This is an interventional treatment trial for Cancer focused on measuring EGFR, FOLFIRI, 2nd Line Therapy, 2nd Line mCRC Therapy, mCRC, Irinotecan, panitumumab, bevacizumab
Eligibility Criteria
Inclusion Criteria
- Diagnosis of metastatic adenocarcinoma of the colon or rectum that cannot, in the opinion of the investigator, be cured by surgical resection at the time of randomization
- Wild-type KRAS expressing mCRC from the primary tumor or metastasis.
- Failure of prior first-line oxaliplatin-based chemotherapy with bevacizumab (at least four therapeutic doses of oxaliplatin-based chemotherapy and bevacizumab) for mCRC.
- At least one uni-dimensionally measurable lesion per modified RECIST criteria.
- Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Man or woman 18 years of age or older
- Hematology, chemistry, coagution, metabolic functions within normal or protocol-defined limits
Exclusion Criteria
- Previous irinotecan, anti-EGFr therapy (eg, cetuximab, panitumumab, erlotinib, gefitinib, lapatinib) or vaccine for the treatment of mCRC
- Radiotherapy ≤ 14 days before randomization
- Evidence of central nervous system (CNS) metastases
- Unresolved toxicities from prior anti-cancer therapy that, in the opinion of the investigator, precludes subject from participation
- History of other invasive primary cancer, except:
- Curatively resected or treated non-melanomatous skin cancer
- Curatively treated cervical carcinoma in situ
- Other primary solid tumor treated curatively and no treatment administered ≤ 2 years before randomization and, in the investigator's opinion, it is unlikely that there will be a recurrence ≤ 2 years post randomization
Medications
- C hronic daily treatment (as determined by the investigator) with aspirin (> 325 mg/day) or non steroidal anti inflammatory agents known to inhibit platelet function
- Infection requiring a course of systemic anti-infectives that was completed ≤ 14 days before randomization (exception can be made at the judgment of the investigator for oral treatment of an uncomplicated urinary tract infection [UTI])
- Subjects concurrently receiving any investigational agent or therapy ≤ 30 days before randomization
General:
- Significant cardiovascular risk as defined by the protocol
- History of peripheral arterial ischemia ≤ 24 weeks before randomization (subjects with brief, reversible, exercise-induced claudication are eligible)
- History of visceral arterial ischemia ≤ 24 weeks before randomization
- Significant bleeding risk:
- Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days before randomization
- Anticipation of need for major surgical procedures during the course of the study
- C ore biopsy or other minor procedure, excluding placement of a vascular access device ≤ 7 days before randomization
- A ny significant bleeding that is not related to the primary colon tumor ≤ 24 weeks before randomization
- P re-existing bleeding diathesis or coagulopathy with the exception of well-controlled chronic anticoagulation therapy
- Serious or non-healing wounds, skin ulcers, or unhealed bone fractures
- Gastroduodenal ulcer(s) determined by endoscopy to be active or uncontrolled gastrointestinal ulcer ≤ 28 days before randomization
- History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest x-ray (CXR) or computed tomography (CT) scan
- Clinically significant ascites
- Subjects known to be human immunodeficiency virus (HIV) positive or known to have chronic or active hepatitis B or C infection
- Men and women of childbearing potential (women who are post-menopausal < 52 weeks, not surgically sterilized, or not abstinent) who do not consent to use adequate contraception (according to institutional standard of care) during the course of the study and after the last date of receiving second-line treatment (24 weeks for women, 4 weeks for men)
- Women who test positive for serum or urine pregnancy test ≤ 72 hours before randomization or are breast-feeding
- Subjects allergic to any component that is part of the treatment regimen
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A
Arm B
Arm Description
FOLFIRI + Panitumumab
FOLFIRI + Bevacizumab
Outcomes
Primary Outcome Measures
Progression-free Survival (PFS)
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
Overall Survival
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
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
Time to response is defined as time from the date of randomization to the date of first confirmed objective response
Time to Progression
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
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
Duration of response is defined as time from first confirmed objective response to disease progression per modified RECIST version 1.0 (by central assessment).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00418938
Brief Title
SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
November 1, 2006 (Actual)
Primary Completion Date
May 10, 2012 (Actual)
Study Completion Date
April 1, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Colon Cancer, Colorectal Cancer, Metastatic Cancer, Rectal Cancer, Metastatic Colorectal Cancer
Keywords
EGFR, FOLFIRI, 2nd Line Therapy, 2nd Line mCRC Therapy, mCRC, Irinotecan, panitumumab, bevacizumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
266 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Description
FOLFIRI + Panitumumab
Arm Title
Arm B
Arm Type
Experimental
Arm Description
FOLFIRI + Bevacizumab
Intervention Type
Drug
Intervention Name(s)
Panitumumab
Intervention Description
6mg/kg IV
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
Either 5mg/kg OR 10mg/kg IV
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Intervention Description
400mg/m^2 IV (in the vein)
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
180mg/m^2 IV (in the vein)
Intervention Type
Drug
Intervention Name(s)
5-Fluorouracil
Intervention Description
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
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
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).
Time Frame
From randomization up to 65 months.
Secondary Outcome Measure Information:
Title
Overall Survival
Description
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 Frame
From randomization up to 65 months.
Title
Objective Response Rate
Description
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 Frame
From randomization up to 65 months.
Title
Time to Response
Description
Time to response is defined as time from the date of randomization to the date of first confirmed objective response
Time Frame
From randomization up to 65 months.
Title
Time to Progression
Description
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).
Time Frame
From randomization up to 65 months.
Title
Disease Control
Description
Disease control is defined as incidence of objective response or stable disease on study up to starting a new anti-tumor therapy.
Time Frame
From randomization up to 65 months.
Title
Duration of Response
Description
Duration of response is defined as time from first confirmed objective response to disease progression per modified RECIST version 1.0 (by central assessment).
Time Frame
From randomization up to 65 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Diagnosis of metastatic adenocarcinoma of the colon or rectum that cannot, in the opinion of the investigator, be cured by surgical resection at the time of randomization
Wild-type KRAS expressing mCRC from the primary tumor or metastasis.
Failure of prior first-line oxaliplatin-based chemotherapy with bevacizumab (at least four therapeutic doses of oxaliplatin-based chemotherapy and bevacizumab) for mCRC.
At least one uni-dimensionally measurable lesion per modified RECIST criteria.
Cooperative Oncology Group (ECOG) performance status of 0 or 1
Man or woman 18 years of age or older
Hematology, chemistry, coagution, metabolic functions within normal or protocol-defined limits
Exclusion Criteria
Previous irinotecan, anti-EGFr therapy (eg, cetuximab, panitumumab, erlotinib, gefitinib, lapatinib) or vaccine for the treatment of mCRC
Radiotherapy ≤ 14 days before randomization
Evidence of central nervous system (CNS) metastases
Unresolved toxicities from prior anti-cancer therapy that, in the opinion of the investigator, precludes subject from participation
History of other invasive primary cancer, except:
Curatively resected or treated non-melanomatous skin cancer
Curatively treated cervical carcinoma in situ
Other primary solid tumor treated curatively and no treatment administered ≤ 2 years before randomization and, in the investigator's opinion, it is unlikely that there will be a recurrence ≤ 2 years post randomization
Medications
C hronic daily treatment (as determined by the investigator) with aspirin (> 325 mg/day) or non steroidal anti inflammatory agents known to inhibit platelet function
Infection requiring a course of systemic anti-infectives that was completed ≤ 14 days before randomization (exception can be made at the judgment of the investigator for oral treatment of an uncomplicated urinary tract infection [UTI])
Subjects concurrently receiving any investigational agent or therapy ≤ 30 days before randomization
General:
Significant cardiovascular risk as defined by the protocol
History of peripheral arterial ischemia ≤ 24 weeks before randomization (subjects with brief, reversible, exercise-induced claudication are eligible)
History of visceral arterial ischemia ≤ 24 weeks before randomization
Significant bleeding risk:
Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days before randomization
Anticipation of need for major surgical procedures during the course of the study
C ore biopsy or other minor procedure, excluding placement of a vascular access device ≤ 7 days before randomization
A ny significant bleeding that is not related to the primary colon tumor ≤ 24 weeks before randomization
P re-existing bleeding diathesis or coagulopathy with the exception of well-controlled chronic anticoagulation therapy
Serious or non-healing wounds, skin ulcers, or unhealed bone fractures
Gastroduodenal ulcer(s) determined by endoscopy to be active or uncontrolled gastrointestinal ulcer ≤ 28 days before randomization
History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest x-ray (CXR) or computed tomography (CT) scan
Clinically significant ascites
Subjects known to be human immunodeficiency virus (HIV) positive or known to have chronic or active hepatitis B or C infection
Men and women of childbearing potential (women who are post-menopausal < 52 weeks, not surgically sterilized, or not abstinent) who do not consent to use adequate contraception (according to institutional standard of care) during the course of the study and after the last date of receiving second-line treatment (24 weeks for women, 4 weeks for men)
Women who test positive for serum or urine pregnancy test ≤ 72 hours before randomization or are breast-feeding
Subjects allergic to any component that is part of the treatment regimen
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
25982297
Citation
Hecht JR, Cohn A, Dakhil S, Saleh M, Piperdi B, Cline-Burkhardt M, Tian Y, Go WY. SPIRITT: A Randomized, Multicenter, Phase II Study of Panitumumab with FOLFIRI and Bevacizumab with FOLFIRI as Second-Line Treatment in Patients with Unresectable Wild Type KRAS Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2015 Jun;14(2):72-80. doi: 10.1016/j.clcc.2014.12.009. Epub 2015 Jan 8.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial
We'll reach out to this number within 24 hrs