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FOLFIRI and Panitumumab in Treating Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02508077
Recruitment Status : Terminated (Poor Accrual)
First Posted : July 24, 2015
Results First Posted : August 16, 2018
Last Update Posted : August 16, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Tracking Information
First Submitted Date  ICMJE July 22, 2015
First Posted Date  ICMJE July 24, 2015
Results First Submitted Date  ICMJE July 20, 2018
Results First Posted Date  ICMJE August 16, 2018
Last Update Posted Date August 16, 2018
Actual Study Start Date  ICMJE February 16, 2016
Actual Primary Completion Date September 13, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2018)
4-month Progression-free Survival (PFS) Rate [ Time Frame: At 4 months ]
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Will be estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including baseline sum), or a measurable increase in a non-target lesion, or the appearance of new lesions.
Original Primary Outcome Measures  ICMJE
 (submitted: July 22, 2015)
  • PFS assessed by the revised RECIST guideline (version 1.1) [ Time Frame: At 4 months ]
    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Will be estimated using the product-limit method of Kaplan and Meier.
  • RR assessed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [ Time Frame: Up to 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2015)
  • Impact of PFS on prior anti-EGFR therapy [ Time Frame: Up to 2 years ]
  • Impact of response on prior anti-EGFR therapy [ Time Frame: Up to 2 years ]
  • Impact of time since last anti-EGFR exposure on the PFS [ Time Frame: Up to 2 years ]
  • Impact of time since last anti-EGFR exposure on the RR [ Time Frame: Up to 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: July 22, 2015)
Mutational status [ Time Frame: Up to 9 months post-treatment ]
Standard descriptive methods will be used to summarize the role of mutational status and other studies. If the combination is not found to have sufficient activity, these patterns may help explain the lack of activity. If sufficient activity is found, then participants who experience an objective response will be compared to those who did not in terms of correlates. Estimates of variation will also prove useful for future clinical research on this regimen.
Descriptive Information
Brief Title  ICMJE FOLFIRI and Panitumumab in Treating Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer
Official Title  ICMJE A Prospective Study of FOLFIRI Plus Panitumumab in Extended RAS Wild Type and BRAF Wild Type Metastatic Colorectal Cancer With Acquired Resistance to Prior Cetuximab (or Panitumumab) Plus Irinotecan-Based Therapy and Who Failed at Least One Subsequent Non-anti-EGFR Containing Regimen
Brief Summary This phase II trial studies how well fluorouracil, leucovorin calcium, and irinotecan hydrochloride (FOLFIRI) together with panitumumab work in treating patients with colorectal cancer that expresses the RAS and B-Raf proto-oncogene, serine/threonine kinase (BRAF) wild-type genes, has spread from the original site of growth to another part of the body (metastatic), resists the effects of treatment with prior cetuximab (or panitumumab) plus irinotecan hydrochloride-based therapy, and who have failed at least one subsequent non-anti-epidermal growth factor receptor (EGFR) containing treatment regimen. Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as panitumumab, may block tumor growth in different ways by targeting certain cells. Giving FOLFIRI together with panitumumab may be an effective treatment for colorectal cancer.
Detailed Description


I. Estimate the response rate (RR) and progression-free survival (PFS) with FOLFIRI + panitumumab in patients with acquired resistance to panitumumab (or cetuximab) + irinotecan (irinotecan hydrochloride)-based therapy after a documented clinical response or prolonged PFS and following progression on a subsequent non-anti-EGFR containing regimen in extended RAS wild-type and BRAF wild-type patients.


I. Estimate the overall survival (OS) in the re-challenge populations.

II. Describe the safety of re-challenge in this population.

III. Investigate the impact of PFS, RR on prior anti-EGFR + irinotecan-based exposure on the response and PFS on the current study.


I. Collect serial plasma samples to investigate the incidence of RAS and BRAF mutation in circulating free deoxyribonucleic acid (DNA) at baseline, every 2 months, and at the time to progression (and following progression when feasible).

II. Collect serial plasma samples for future biomarker exploration, including the potential investigation of micro-ribonucleic acid (RNA).


Patients receive panitumumab intravenously (IV) over 30-90 minutes, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium orally (PO), and fluorouracil IV over 46 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Colorectal Carcinoma
  • Stage IVA Colorectal Cancer
  • Stage IVB Colorectal Cancer
Intervention  ICMJE
  • Drug: Fluorouracil
    Given IV
    Other Names:
    • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
    • 5-Fluorouracil
    • 5-Fluracil
    • 5-FU
    • AccuSite
    • Actino-Hermal
    • Adrucil
    • Arumel
    • Cytosafe
    • Efudex
    • Efurix
    • Fiverocil
    • Fluoro Uracil
    • Fluoroplex
    • Fluouracil
    • Flurablastin
    • Fluracedyl
    • Fluracil
    • Fluril
    • Fluroblastin
    • Flurox
    • Ribofluor
    • Ro 2-9757
    • Ro-2-9757
    • Timazin
  • Drug: Irinotecan Hydrochloride
    Given IV
    Other Names:
    • Campto
    • Camptosar
    • Camptothecin 11
    • Camptothecin-11
    • CPT 11
    • CPT-11
    • U-101440E
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Leucovorin Calcium
    Given PO
    Other Names:
    • Adinepar
    • Calcifolin
    • Calcium (6S)-Folinate
    • Calcium Folinate
    • Calcium Leucovorin
    • Calfolex
    • Calinat
    • Cehafolin
    • Citofolin
    • Citrec
    • Citrovorum Factor
    • Cromatonbic Folinico
    • Dalisol
    • Disintox
    • Divical
    • Ecofol
    • Emovis
    • Factor, Citrovorum
    • Flynoken A
    • Folaren
    • Folaxin
    • FOLI-cell
    • Foliben
    • Folidan
    • Folidar
    • Folinac
    • Folinate Calcium
    • folinic acid
    • Folinic Acid Calcium Salt Pentahydrate
    • Folinoral
    • Folinvit
    • Foliplus
    • Folix
    • Imo
    • Lederfolat
    • Lederfolin
    • Leucosar
    • leucovorin
    • Rescufolin
    • Rescuvolin
    • Tonofolin
    • Wellcovorin
  • Biological: Panitumumab
    Given IV
    Other Names:
    • ABX-EGF
    • ABX-EGF Monoclonal Antibody
    • ABX-EGF, Clone E7.6.3
    • MoAb ABX-EGF
    • Monoclonal Antibody ABX-EGF
    • Vectibix
Study Arms  ICMJE Experimental: Treatment (panitumumab and FOLFIRI)
Patients receive panitumumab IV over 30-90 minutes, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium PO, and fluorouracil IV over 46 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
  • Drug: Fluorouracil
  • Drug: Irinotecan Hydrochloride
  • Other: Laboratory Biomarker Analysis
  • Drug: Leucovorin Calcium
  • Biological: Panitumumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 15, 2017)
Original Estimated Enrollment  ICMJE
 (submitted: July 22, 2015)
Actual Study Completion Date  ICMJE September 13, 2017
Actual Primary Completion Date September 13, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participant must have the ability to understand and the willingness to sign a written informed consent document
  • Participant must be willing to comply with study and/or follow-up procedures
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy of 3 >= months
  • Histologically confirmed colon or rectal cancer with metastatic disease
  • Extended RAS and BRAF wild type status documented on archival tumor tissue or on fresh biopsy if no archival tissue present
  • Measurable disease defined by at least 1 lesion >= 1 cm
  • Documented objective response or stable disease lasting for 6 months or more to last prior anti-EGFR (cetuximab or panitumumab) in combination with irinotecan or FOLFIRI
  • Progression within 6 weeks following their last dose of anti-EGFR therapy
  • Treatment with a non-EGFR targeting regimen following progression on anti-EGFR plus irinotecan-based therapy
  • At least 4 months from prior anti-EGFR therapy prior to start of study treatment
  • At least three weeks from any non-anti-EGFR therapy prior to start of study treatment; any number of prior therapies is permitted
  • Adequate recovery in the investigators opinion from any clinically significant toxicity from prior therapy
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Hemoglobin (Hgb) >= 9 g/dL without transfusions
  • Platelets (PLT) >= 100 x 10^9/L without transfusions
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x upper limit of normal (ULN); patient with liver metastases =< 5 x ULN
  • Total bilirubin =< ULN
  • Creatinine =< 1.5 mg/dL
  • Magnesium >= 1.2mg/dL or 0.5 mmol/L
  • Negative serum beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only), to be performed locally within the screening period
  • Agreement by females of childbearing potential and sexually active males to use an effective method of contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for three months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

Exclusion Criteria:

  • History of severe anti-EGFR toxicity requiring drug discontinuation or dose-modification within the first 4 months of prior anti-EGFR therapy
  • History of intolerance to irinotecan at dose-intensity of 125 mg/m^2/2 weeks or lower
  • History of intolerance to 5-FU at dose-intensity of 1800 mg/m^2/2 weeks or lower
  • Current use (or planned use during the treatment period) of other investigational agents, or biological, chemotherapy, radiation or other anti-tumor therapy
  • Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids, such as systemic cyclosporine and tacrolimus
  • No St John's wort supplement or other herbal supplementation is allowed while on trial; patients are not to take grapefruit juice during study treatment
  • Use of drugs known to inhibit UDP glycosyltransferase 1 family, polypeptide A1 gene (UGT1A1), such as Atazanavir, Gemfibrozil, Indinavir, or Ketoconazole while on study treatment; (patients using these drugs must not take these drugs on the day study treatment begins and for the duration of study treatment)
  • Planned use of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors or CYP3A4 inducers while on study treatment unless deemed clinically necessary with no reasonable alternatives and with expressed permission from the principal investigator
  • If on anticoagulation, participant must be on stable therapeutic dose prior to enrollment
  • Impairment of gastrointestinal function or gastrointestinal disease (e.g., active ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, extensive small bowel resection)
  • Major surgery =< 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure
  • Unstable pulmonary embolism, deep vein thrombosis, or other significant arterial/venous thromboembolic event =< 30 days before enrollment
  • Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) =< 6 months prior to enrollment
  • History of interstitial lung disease (ILD) eg, interstitial pneumonitis, pulmonary fibrosis or evidence of ILD on baseline chest computed tomography (CT) or magnetic resonance imaging (MRI)
  • Other active malignancies except cervical carcinomas in situ or clinically insignificant non-melanoma skin cancers
  • Clinically significant uncontrolled illness or active infections
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan, 5-FU, leucovorin or any of the products to be administered during dosing
  • Pregnant women and women who are lactating; breastfeeding should be discontinued if the mother is enrolled on this study
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/psychological issues, etc
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02508077
Other Study ID Numbers  ICMJE 15117
NCI-2015-01241 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
15117 ( Other Identifier: City of Hope Comprehensive Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party City of Hope Medical Center
Study Sponsor  ICMJE City of Hope Medical Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Marwan Fakih City of Hope Comprehensive Cancer Center
PRS Account City of Hope Medical Center
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP