CancerPhase 2NCT00418938
SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial
A Phase 2 study testing Panitumumab, Bevacizumab and Leucovorin in people with Cancer and Colon Cancer, run by Amgen.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Colon Cancer, Colorectal Cancer
- What is being tested?
- Panitumumab, Bevacizumab and Leucovorin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 266 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2006to 1 Apr 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 30Show fewer
- 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
About this study
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
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).
Read the 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.
- Conditions
- Cancer, Colon Cancer, Colorectal Cancer, Metastatic Cancer, Rectal Cancer, Metastatic Colorectal Cancer
- Being tested
- Panitumumab, Bevacizumab, Leucovorin, Irinotecan, 5-Fluorouracil
- Keywords
- EGFR, FOLFIRI, 2nd Line Therapy, 2nd Line mCRC Therapy, mCRC, Irinotecan, panitumumab, bevacizumab
- Medical subject headings
- Neoplasms, Colonic Neoplasms, Colorectal Neoplasms, Neoplasm Metastasis, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanitumumabDrug
6mg/kg IV
BevacizumabDrug
Either 5mg/kg OR 10mg/kg IV
LeucovorinDrug
400mg/m^2 IV (in the vein)
IrinotecanDrug
180mg/m^2 IV (in the vein)
5-FluorouracilDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | FOLFIRI + Panitumumab Receives: Drug: Panitumumab; Drug: Leucovorin; Drug: Irinotecan; Drug: 5-Fluorouracil |
| Arm B | Experimental | FOLFIRI + Bevacizumab Receives: Drug: Bevacizumab; Drug: Leucovorin; Drug: Irinotecan; Drug: 5-Fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From randomization up to 65 months.
Secondary outcomes (6)
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.
Measured: From randomization up to 65 months.
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.
Measured: From randomization up to 65 months.
Time to Response
Time to response is defined as time from the date of randomization to the date of first confirmed objective response
Measured: From randomization up to 65 months.
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).
Measured: From randomization up to 65 months.
Disease Control
Disease control is defined as incidence of objective response or stable disease on study up to starting a new anti-tumor therapy.
Measured: From randomization up to 65 months.
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).
Measured: From randomization up to 65 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2007 (estimated)
- Study start1 Nov 2006
- Primary completion10 May 2012
- Study completion1 Apr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 266 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00418938
- Sponsor's protocol ID
- 20060141
- Status last verified
- Sep 2018
- First submitted
- 4 Jan 2007
- Last updated
- 17 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 25982297
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00418938
- Acronym / sponsor ID
- 20060141
- Conditions
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 266 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 1 Nov 2006 (actual)
- Primary completion
- 10 May 2012 (actual)
- Study completion
- 1 Apr 2013 (actual)
- First posted
- 5 Jan 2007 (estimated)
- Results
- Posted 28 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Panitumumab, Drug: Leucovorin, Drug: Irinotecan, Drug: 5-FluorouracilFOLFIRI + Panitumumab |
| Arm B | Experimental | Drug: Bevacizumab, Drug: Leucovorin, Drug: Irinotecan, Drug: 5-FluorouracilFOLFIRI + Bevacizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (30 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Panitumumab6mg/kg IV | Drug | Arm A |
| BevacizumabEither 5mg/kg OR 10mg/kg IV | Drug | Arm B |
| Leucovorin400mg/m^2 IV (in the vein) | Drug | Arm A, Arm B |
| Irinotecan180mg/m^2 IV (in the vein) | Drug | Arm A, Arm B |
| 5-Fluorouracil400mg/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 | Drug | Arm A, Arm B |
Primary outcome
Progression-free Survival (PFS)
Time frame: 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).
6 secondary outcomes
Overall Survival
Time frame: From randomization up to 65 months.
Objective Response Rate
Time frame: From randomization up to 65 months.
Time to Response
Time frame: From randomization up to 65 months.
Time to Progression
Time frame: From randomization up to 65 months.
Disease Control
Time frame: From randomization up to 65 months.
Duration of Response
Time frame: From randomization up to 65 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25982297Hecht 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Panitumumab, Bevacizumab and Leucovorin in people with Cancer and Colon Cancer, run by Amgen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (time frame: From randomization up to 65 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00418938, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2018.