Panitumumab and Chemotherapy in Patients With Advanced Colorectal Cancer After Prior Therapy With Bevacizumab

NCT01814501 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: OSU-11131NCI-2013-00432
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well panitumumab and combination chemotherapy works in treating patients with metastatic colorectal cancer previously treated with combination chemotherapy and bevacizumab. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panitumumab and combination chemotherapy together may kill more tumor cells

Conditions

Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

Keywords

Metastatic colon cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Continuous variables will be expressed by means, standard deviations and 95% confidence intervals. Estimated using the Kaplan-Meier estimator with confidence interval calculated based on the Brookmeyer-Crowley method.

  Time from study day 1 to the time the patient is first recorded as having disease progression or death, assessed up to 3 years

Secondary Outcomes (3)

• Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0

  Up to 3 years

• Proportion of Participants With Overall Response Rate, as Described in RECIST v1.1 Criteria

  Up to 3 years

• Overall Survival

  Time from study day 1 to the date of death or the last date the patient was known to be alive, assessed up to 3 years

Study Arms (1)

Treatment (panitumumab, combination chemotherapy)

EXPERIMENTAL

5-Fluorouracil, irinotecan, and panitumumab

Biological: panitumumab; Drug: irinotecan hydrochloride; Drug: fluorouracil; Drug: leucovorin calcium

Interventions

panitumumab BIOLOGICAL

Each vial of panitumumab will contain 20 mL of a sterile protein solution containing a 20-mg/mL solution of panitumumab. The vial will contain approximately 400mg of panitumumab and is for single dose use only.

Also known as: ABX-EGF, MOAB ABX-EGF, monoclonal antibody ABX-EGF, Vectibix

Treatment (panitumumab, combination chemotherapy)

irinotecan hydrochloride DRUG

Diluted with 5% dextrose (D5W) to a total volume of 500 mL and infused intravenously over 90 minutes. Nothing else should be added to the bag. Patients will be given a dose of 180 mg/M2 by intravenous infusion.

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

Treatment (panitumumab, combination chemotherapy)

fluorouracil DRUG

Administered intravenously. A bolus of 400 mg/m2 to be followed by a continuous infusion over 46 hrs at a dose of 2400mg/m2.

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Treatment (panitumumab, combination chemotherapy)

leucovorin calcium DRUG

Leucovorin will be administered at a dose of 200 mg/m2 over 120 minutes prior to the 5-FU bolus. Leucovorin may be run simultaneously with irinotecan infusion via y-site connection.

Also known as: CF, CFR, LV

Treatment (panitumumab, combination chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Patients with advanced adenocarcinoma of the colon or rectum not curable with surgery or radiotherapy and have been previously treated for their disease with FOLFIRI plus bevacizumab in the first line metastatic setting; patients will only be eligible if their last line of therapy prior to enrolling onto the study was FOLFIRI and bevacizumab received no more than 6 months prior to enrolling in this study; they should have been treated with FOLFIRI plus bevacizumab until disease progression is radiographically documented
• Patients' tumors will need to tested for the K-RAS and N-RAS mutation status; only those patients with wild-type or unmutated K-RAS and N-RAS oncogene are eligible to participate in this study
• Provide written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
• Prior cetuximab is allowed in the adjuvant but not in the metastatic setting, but must have been completed at least 6 months before starting this trial
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Life expectancy greater than 12 weeks
• No active brain metastasis; previously surgically treated or irradiated lesions are allowed if not clinically active
• Has a negative serum pregnancy test within 7 days prior to registration (female patients of childbearing potential)
• Ability to understand and willingness to sign a written informed consent
• No history of severe reactions to fluorouracil (5-FU), irinotecan (irinotecan hydrochloride), or a monoclonal antibody
• Leukocytes \>= 3000/uL
• Absolute neutrophil count \>= 1500/uL
• Platelets \>= 100,000/uL
• Hemoglobin \>= 9 mg/dL
• Total bilirubin =\< 1.5 X upper limit of normal (ULN)

You may not qualify if:

• Pregnant or lactating women; women of childbearing potential with either a positive or no pregnancy test at baseline; woman or men of childbearing potential not using a reliable and appropriate contraceptive method; (postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential)
• Sexually active males unwilling to practice contraception during the study and 6 months beyond
• Uncontrolled intercurrent illness including but not limited to clinically significant cardiac disease not well controlled with medication (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias) or myocardial infarction within the last 12 months, and serious concurrent infections
• History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan
• KRAS or NRAS mutant tumors
• Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as \>= Common Toxicity Criteria \[CTC\] grade 2 \[Common Terminology Criteria for Adverse Events (CTCAE) version 4.0\])
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) =\< 1 year
• Bevacizumab within the last 4 weeks before starting treatment on trial
• Patient is more than 6 months since the last dose of FOLFIRI
• Patients who have required toxicity related dose reductions of no less than 50% of the original dose of infusional 5-FU and/or irinotecan during the administration of FOLFIRI + bevacizumab
• Prior exposure to panitumumab in any setting
• Prior exposure to cetuximab in the metastatic (stage IV) setting
• Radiotherapy =\< 14 days prior to enrollment; patients must have recovered from all radiotherapy-related toxicities
• Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil, leucovorin (leucovorin calcium), irinotecan, or panitumumab
• Treatment for other carcinomas within the last three years, except cured non-melanoma skin and treated in-situ cervical cancer

Sponsors & Collaborators

• John Hays: lead
• Amgen: collaborator

Study Sites (2)

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Panitumumab; Irinotecan; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; 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; Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Dr. John Hays
• Organization: The Ohio State University Comprehensive Cancer Center

John.Hays@osumc.edu

614-293-3873

Study Officials

• John Hays, MD

  Ohio State University 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 INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 25, 2013
• First Posted: March 20, 2013
• Study Start: February 1, 2013
• Primary Completion: August 6, 2018
• Study Completion: August 6, 2018
• Last Updated: February 5, 2025
• Results First Posted: February 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)