Back to results

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

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

NCT ID

NCT00418938

First Posted

January 4, 2007

Last Updated

September 20, 2018

Sponsor

Amgen

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

Time Frame