Re-challenge Therapy With Chemotherapy & Panitumumab in Metastatic Colorectal Cancer Patients Treated With an Anti-EGFR

NCT ID: NCT03940131

Last Updated: 2022-04-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-10
• Study Completion Date: 2022-07-31

Brief Summary

patients with metastatic colorectal cancer who were initially RAS wild and failed at least 2 lines of chemotherapy will be enrolled. Anti-EGFR must have been given in 1st line. Those who remain RAS-wild upon retesting will receive rechallenge with panitumumab and chemotherapy

Detailed Description

This is a single arm pilot multicenter prospective study. We will recruit KRAS/RAS wild metastatic colorectal cancer patients who received at least 2 lines of chemotherapy and the 1st line must include cetuximab/panitumumab combined with chemotherapy. We will repeat RAS testing after progression on the last line of therapy. RAS testing will be taken via liquid biopsy using ctDNA or tissue biopsy from either a new tumour lesion or a previously present lesion which shows evidence of disease progression by radiological imaging. Only RAS-wild patients upon re-testing will be enrolled and will receive re-challenge therapy with panitumumab combined with chemotherapy similar to that given at 1st line (5-fluorouracil/leucoverin combined with oxaliplatin or irinotecan). Those converted to RAS mutant will not be enrolled.

All patients will be treated until disease progression, unacceptable toxic effects or withdrawal of consent.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm

Panitumumab with FOLFOX6/FOLFIRI

Group Type: EXPERIMENTAL

Panitumumab

Intervention Type: DRUG

FOLFOX6 regimen consists of 2-hour infusion of oxaliplatin (85 mg/m2) and 2-hour infusion of leucovorin (400 mg/m2 ) on Day l, followed by 5-fluorouracil bolus (400 mg/m2) on Day 1 and 46-hour infusion (2.4 g/m2). FOLFOX6 regimen will be repeated at 2-week intervals. FOLFIRI regimen consists of 2-hour infusion of irinotecan (180 mg/m2) and 2-hour infusion of leucovorin (400 mg/m2 ) on Day l, followed by 5-fluorouracil bolus (400 mg/m2) on Day 1 and 46-hour infusion (2.4 g/m2). FOLFIRI regimen will be repeated at 2-week intervals.

Interventions

Panitumumab

FOLFOX6 regimen consists of 2-hour infusion of oxaliplatin (85 mg/m2) and 2-hour infusion of leucovorin (400 mg/m2 ) on Day l, followed by 5-fluorouracil bolus (400 mg/m2) on Day 1 and 46-hour infusion (2.4 g/m2). FOLFOX6 regimen will be repeated at 2-week intervals. FOLFIRI regimen consists of 2-hour infusion of irinotecan (180 mg/m2) and 2-hour infusion of leucovorin (400 mg/m2 ) on Day l, followed by 5-fluorouracil bolus (400 mg/m2) on Day 1 and 46-hour infusion (2.4 g/m2). FOLFIRI regimen will be repeated at 2-week intervals.

Intervention Type: DRUG

Other Intervention Names

Folfox; Folfiri

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed metastatic adenocarcinoma of the colon or rectum with initially KRAS/RAS wild tumours.
• Patients received at least 2 lines of chemotherapy including a fluoropyrimidine, irinotecan and oxaliplatin± bevacizumab.
• First line chemotherapy regimen with a fluoropyrimidine and irinotecan or fluoropyrimidine and oxaliplatin in addition to an anti-EGFR agent (cetuximab/panitumumab).
• No evidence of disease progression for at least 4 months from the start of 1st line therapy.
• At least one measurable lesion ≥ 10 mm as assessed by CT-scan or MRI must be available and accessible for re-biopsy and RAS testing.
• Repeated RAS testing before re-challenge therapy must be done.
• Age ≥18 years.
• ECOG Performance status (PS) 0-2.
• The patient has adequate organ function, defined as : Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, hemoglobin ≥ 9 g/dl, and platelets ≥ 100 x 109/L. Total bilirubin ≤ 1.5 times upper limit of normal value (ULN), serum alkaline phosphatase level < 5 times ULN, Serum creatinine level <1.5 mg/dl.
• For female patients of childbearing potential, negative pregnancy test within 7 days before starting the study treatment.
• Subject must provide informed consent prior to initiation of any study specific activities/procedures

Exclusion Criteria

• Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiation of study treatment or a history of ventricular arrhythmia (treated or not).
• History or evidence of central nervous system metastasis (CT-scan or MRI are not mandatory if no clinical symptoms).
• Known allergy or hypersensitivity to panitumumab.
• Patients with right-sided colon cancer originating from the ascending colon or hepatic flexure.
• Patients with known MSI-high status.
• Patients with known HER2-positive status.
• Previous or concurrent malignancy except for basal or squamous cell skin cancer, in situ carcinoma of the cervix, low-risk prostate cancer according to d'Amico classification or other solid tumors treated curatively and without evidence of recurrence for at least 5 years prior to the study.
• Active or uncontrolled clinically serious infection.
• Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness.
• Other serious and uncontrolled non-malignant disease.
• Pregnancy.
• Breast feeding.
• Treatment with any other investigational medicinal product within 28 days prior to study entry.
• Concomitant administration of live, attenuated virus vaccine such as yellow fever vaccine.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

King Abdullah Medical City

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shereef A Elsamany, MD

Role: PRINCIPAL_INVESTIGATOR

King Abdullah Medical City

Locations

King Abdullah Medical City, Holy Capital

Mecca, Makkah Western, Saudi Arabia

Site Status: RECRUITING

Countries

Saudi Arabia

Central Contacts

Shereef A Elsamany, MD

Role: CONTACT

shereefmohamad@yahoo.com

+96625549999 ext. 13721

Rania M Felemban, MSc

Role: CONTACT

raniafelemban@gmail.com

+96625549999 ext. 18013

Facility Contacts

Rania M Felemban, Msc

Role: primary

felembanr@kamc.med.sa

0096625549999 ext. 18013

Wedian O Almowlad, Msc

Role: backup

Almwlld.W@kamc.med.sa

0096625549999 ext. 18004

Other Identifiers

19-504

Identifier Type: -

Identifier Source: org_study_id