5-FU Based Maintenance Therapy in RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX Plus Panitumumab

NCT03300609 | Terminated Phase 3 DMC FDA Drug

• 3 other identifiers: 3C-16-6NCI-2017-01414P30CA014089
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized trial studies how well panitumumab, leucovorin calcium, and fluorouracil after combination chemotherapy and panitumumab induction work in treating patients with RAS wild type colorectal cancer that has spread from where it started to nearby tissue or lymph nodes or other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, 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 panitumumab, leucovorin calcium, and fluorouracil after combination chemotherapy and panitumumab induction may work better in treating patients with colorectal cancer.

Conditions

Colorectal Adenocarcinoma; RAS Wild Type; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Progression free survival 1

  Disease progression will be determined by comparing tumor measurement during maintenance therapy to baseline measurement before starting maintenance treatment using Response Evaluation Criteria in Solid Tumors 1.1. will be conducted based on the intent-to-treat population from the time of randomization.

  From the date of randomization to the date of 1st documented disease progression or death due to any cause, whichever occurs first, assessed up to 7 months.

Secondary Outcomes (1)

• Treatment Response

  Up to 4 years

Study Arms (2)

Arm I (panitumumab, leucovorin calcium, fluorouracil)

EXPERIMENTAL

INDUCTION Patients receive panitumumab IV over 30-60 minutes, oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive panitumumab IV over 30 minutes, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Biological: Panitumumab; Drug: Oxaliplatin; Drug: Leucovorin Calcium; Drug: Fluorouracil; Other: Quality-of-Life Assessment; Other: Laboratory Biomarker Analysis

Arm II (capecitabine)

ACTIVE COMPARATOR

INDUCTION Patients receive panitumumab IV over 30-60 minutes, oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil over 46-48 hours on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive capecitabine PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: Panitumumab; Drug: Oxaliplatin; Drug: Leucovorin Calcium; Drug: Fluorouracil; Drug: Capecitabine; Other: Quality-of-Life Assessment; Other: Laboratory Biomarker Analysis

Interventions

Panitumumab BIOLOGICAL

Given IV

Also known as: 339177-26-3, ABX-EGF, ABX-EGF Monoclonal Antibody, Clone E7.6.3, MoAb ABX-EGF, Monoclonal Antibody ABX-EGF, Vectibix

Arm I (panitumumab, leucovorin calcium, fluorouracil); Arm II (capecitabine)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, 266046, 61825-94-3, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, oxalato (1R,2R-cyclohexanediamine)platinum(II), oxalato (trans-l-1,2-diaminocyclohexane)platinum(II), Oxalatoplatin, Oxalatoplatinum, RP-54780, SR-96669, trans-l DACH oxalatoplatinum, trans-l diaminocyclohexane oxalatoplatinum

Arm I (panitumumab, leucovorin calcium, fluorouracil); Arm II (capecitabine)

Leucovorin Calcium DRUG

Given IV

Also known as: 1492-18-8, 5-Formyl Tetrahydrofolate, 5-Formyl-5,6,7,8-tetrahydrofolic Acid, 5-Formyl-5,6,7,8-tetrahydropteroyl-L-glutamic Acid, Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Fusilev, Lederfolat, Lederfolin, Leucosar, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Arm I (panitumumab, leucovorin calcium, fluorouracil); Arm II (capecitabine)

Fluorouracil DRUG

Given IV

Also known as: 19893, 2,4-Dioxo-5-fluoropyrimidine, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluoro-2,4(1H,3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, 51-21-8, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Arm I (panitumumab, leucovorin calcium, fluorouracil); Arm II (capecitabine)

Capecitabine DRUG

Given PO

Also known as: 154361-50-9, 5'-Deoxy-5-fluoro-N-[(pentyloxy)carbonyl]-cytidine, 712807, Ro 09-1978/000, Xeloda

Arm II (capecitabine)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (panitumumab, leucovorin calcium, fluorouracil); Arm II (capecitabine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (panitumumab, leucovorin calcium, fluorouracil); Arm II (capecitabine)

Eligibility Criteria

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

You may qualify if:

• Metastatic or locally advanced (unresectable) colorectal cancer with histological confirmation of adenocarcinoma (patients with or without measurable disease by imaging are eligible)
• No prior systemic chemotherapy for metastatic disease; subjects who received adjuvant therapy with FOLFOX and at the time of recurrence are at least 6 months away from last chemotherapy are eligible for this study
• At the time of randomization to maintenance therapy only patients who didn't progress by Response Evaluation Criteria in Solid Tumors (RECIST) criteria are eligible; patients with complete response (CR) and those who are candidates for resection will not be eligible for randomization to maintenance therapy, subjects who undergo surgery potentially have curable disease with defined duration of treatment and use of EGFR in the adjuvant setting is deemed to be detrimental in these population; likelihood of achieving CR is low and standard of care in this unique patient population is not well defined
• Provide written informed consent
• RAS wild-type tumor
• Negative serum or urine pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
• Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0 or 1
• Total serum bilirubin =\< institutional upper limit of normal (ULN)
• Absolute neutrophil count (ANC) \>= 1500/mm\^3
• Platelet count \>= 100,000/mm\^3
• Hemoglobin \>= 9.0 g/dL (hemoglobin may be supported by transfusion)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer)
• Creatinine within institutional limits of normal OR creatinine clearance \> 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Magnesium \>= lower limit of normal
• Willing to provide tissue and blood samples for mandatory correlative and research purposes

You may not qualify if:

• Patients who are candidates for upfront metastasectomy (defined as those with limited liver metastatic disease) are not eligible for this study; the candidacy for resectability can be determined by the treating physician and or local surgeon; in ambiguous situations, please discuss the case with the principle investigator (PI)
• Known or suspected brain or central nervous system (CNS) metastases
• Active, uncontrolled infection, including hepatitis B, hepatitis C
• Patients with history of interstitial lung disease/pulmonary fibrosis
• Concurrent anti-cancer therapy, including chemotherapy agents, targeted agents, or biological agents not otherwise specified in this protocol
• Radiation therapy =\< 2 weeks prior to randomization
• Any of the following
• Pregnant or nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease, history of any psychiatric or addictive disorder, or laboratory abnormality, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Patients known to be human immunodeficiency virus (HIV) positive
• Uncontrolled intercurrent illness whom in the opinion of the investigator, may increase the risks associated with study participation or study treatment, or may interfere with the conduct of the study or the interpretation of the study results
• Receiving any other investigational agent, which would be considered as a treatment for the primary neoplasm
• Other active malignancy =\< 3 years prior to registration; exceptions are: nonmelanoma skin cancer or carcinoma-in-situ of the cervix that has been treated
• History of prior malignancy for which patient is receiving other specific treatment for their cancer

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator
• Amgen: collaborator

Study Sites (1)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Panitumumab; Oxaliplatin; Leucovorin; Levoleucovorin; Fluorouracil; dehydroftorafur; Capecitabine

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Afsaneh Barzi, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2017
• First Posted: October 3, 2017
• Study Start: February 27, 2018
• Primary Completion: October 3, 2019
• Study Completion: October 3, 2019
• Last Updated: June 11, 2020

Record last verified: 2020-06

Locations

US (1)