SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial

September 20, 2018 updated by: Amgen

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
266

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm A
FOLFIRI + Panitumumab
Drug: Panitumumab
6mg/kg IV
Drug: Leucovorin
400mg/m^2 IV (in the vein)
Drug: Irinotecan
180mg/m^2 IV (in the vein)
Drug: 5-Fluorouracil
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
Experimental: Arm B
FOLFIRI + Bevacizumab
Drug: Leucovorin
400mg/m^2 IV (in the vein)
Drug: Irinotecan
180mg/m^2 IV (in the vein)
Drug: 5-Fluorouracil
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
Drug: Bevacizumab
Either 5mg/kg OR 10mg/kg IV

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
From randomization up to 65 months.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 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.
From randomization up to 65 months.
Objective Response Rate
Time Frame: 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.
From randomization up to 65 months.
Time to Response
Time Frame: 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
From randomization up to 65 months.
Time to Progression
Time Frame: 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).
From randomization up to 65 months.
Disease Control
Time Frame: 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.
From randomization up to 65 months.
Duration of Response
Time Frame: 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).
From randomization up to 65 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 10, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 4, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 4, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 5, 2007

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 17, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 20, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20060141

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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