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

NCT02508077 | Terminated Phase 2 Results DMC

• 3 other identifiers: 15117NCI-2015-01241118713
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 4

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.

Conditions

Recurrent Colorectal Carcinoma; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• 4-month Progression-free Survival (PFS) Rate

  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.

  At 4 months

Study Arms (1)

Treatment (panitumumab and FOLFIRI)

EXPERIMENTAL

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

Interventions

Fluorouracil DRUG

Given IV

Also known as: 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

Treatment (panitumumab and FOLFIRI)

Irinotecan Hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, U-101440E

Treatment (panitumumab and FOLFIRI)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (panitumumab and FOLFIRI)

Leucovorin Calcium DRUG

Given PO

Also known as: 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

Treatment (panitumumab and FOLFIRI)

Panitumumab BIOLOGICAL

Given IV

Also known as: ABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, MoAb ABX-EGF, Monoclonal Antibody ABX-EGF, Vectibix

Treatment (panitumumab and FOLFIRI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope Antelope Valley

Lancaster, California, 93534, United States

Location

City of Hope Rancho Cucamonga

Rancho Cucamonga, California, 91730, United States

Location

South Pasadena Cancer Center

South Pasadena, California, 91030, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; dehydroftorafur; Irinotecan; Leucovorin; Panitumumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Study was terminated early due to poor accrual.

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-218-5265

Study Officials

• Marwan Fakih

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2015
• First Posted: July 24, 2015
• Study Start: February 16, 2016
• Primary Completion: September 13, 2017
• Study Completion: September 13, 2017
• Last Updated: August 16, 2018
• Results First Posted: August 16, 2018

Record last verified: 2018-07

Locations

US (4)