Early-Line Anti-EGFR Therapy to Facilitate Retreatment for Select Patients With mCRC

NCT04587128 | Active Not Recruiting Phase 2 DMC FDA Drug

• 5 other identifiers: 2020-0714NCI-2020-06543A534260SMPH/MEDICINE/HEM-ONCProtocol Version 6/17/2025
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The study will use previously established doses of panitumumab or cetuximab in the metastatic setting for the treatment of unresectable colorectal cancer (CRC). It is designed to investigate an alternative treatment strategy to maximize the benefit to inhibition of epidermal growth factor receptor (EGFR) for a highly selected patient population. It will enroll 71 participants with left-sided, unresectable metastatic CRC. Participants will be on study up to 5 years.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Disease Control Rate (DCR) at 6 months for Cohorts A and B

  The disease control rate is the proportion of all subjects with stable disease (SD) for 8 weeks, or partial response (PR), or complete response (CR) according to RECIST 1.1, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).

  6 months

• Cohort C Progression Free Survival (PFS)

  PFS will be defined as the duration (in months) from the date of study enrollment to date of disease progression (or death). If no progression (or death) event is observed during the follow-up period of the study, then PFS will be censored at the last date of follow-up per standard RECIST vs. 1.1 evaluation.

  up to 4 years

Secondary Outcomes (5)

• Cohort A and B Progression Free Survival (PFS)

  up to 4 years

• Cohort A, B, and C Objective Response Rate (ORR)

  up to 1 year

• Type and Severity of Toxicities

  up to 1 year (adverse events collected to 30 days post treatment)

• Rate of Retreatment with EGFRi for Cohorts A and B

  up to 4 years

• Cohort A, B, and C Overall Survival (OS)

  up to 4 years

Other Outcomes (2)

• Change in Participant Derived Organotypic Spheroid Response over baseline

  baseline, post treatment (up to 1 year)

• Circulating Tumor DNA (ctDNA) at time of Progression

  1 month (cycle 1, day 1 of 28 cycle), 4 months (cycle 3, day 1 of 28 day cycle), up to 1 year (30 days post treatment)

Study Arms (3)

Cohort A: No Previous EGFR

EXPERIMENTAL

Participant who have not be previously exposed to anti-EGFR therapies and are in the first or second-line metastatic treatment setting. Panitumumab (6mg/kg) or Cetuximab 500mg (per treating physician) on day 1 and 15 of a 28-day cycle

Drug: Panitumumab; Drug: Cetuximab

Cohort B: Retreatment

EXPERIMENTAL

Participants with treatment refractory disease who have previously benefitted (greater than or equal to 4 months ago) from anti-EGFR therapy. Panitumumab (6mg/kg) or Cetuximab 500mg (per treating physician) on day 1 and 15 of a 28-day cycle, +/- Irinotecan (180mg/m\^2) every 2 two weeks per standard of care

Drug: Panitumumab; Drug: Cetuximab; Drug: Irinotecan

Cohort C: Rechallenge

EXPERIMENTAL

Participants with prior FOLFOX and either no prior EGFR inhibitor or treated on Cohort A. Alternating Panitumumab (6mg/kg) or Cetuximab 500mg (per treating physician) and 4 cycles of FOLFIRI +/- bevacizumab

Drug: Panitumumab; Drug: Cetuximab; Drug: FOLFIRI Protocol; Drug: Bevacizumab

Interventions

Panitumumab DRUG

Epidermal growth factor receptor inhibitor, anti-neoplastic

Cohort A: No Previous EGFR; Cohort B: Retreatment; Cohort C: Rechallenge

Cetuximab DRUG

Epidermal growth factor receptor inhibitor, anti-neoplastic

Cohort A: No Previous EGFR; Cohort B: Retreatment; Cohort C: Rechallenge

Irinotecan DRUG

anti-neoplastic, chemotherapy drug

Cohort B: Retreatment

FOLFIRI Protocol DRUG

folinic acid (also called leucovorin, calcium folinate or FA) fluorouracil (also called 5FU) irinotecan given per institutional standard (intravenously day 1 and day 15 of 28 day cycle) alternating and not concomitant with panitumumab or cetuximab

Cohort C: Rechallenge

Bevacizumab DRUG

Bevacizumab (or biosimilar) may be administered with FOLFIRI per treating MD discretion and will be given per institutional standard (5 mg/kg intravenously day 1 and day 15 of 28 day cycle)

Cohort C: Rechallenge

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information
• As determined by the enrolling physician or protocol designee, ability of the participant to understand and comply with study procedures for the entire length of the study
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
• Have a diagnosis of histologically confirmed metastatic colorectal cancer with primary tumor located beyond the splenic flexure. Histologic confirmation of a colorectal primary tumor is acceptable if accompanied by radiographic evidence of metastatic disease.
• For Cohort A: Participants must enroll for study treatment in the first or second-line metastatic setting. Participants may receive 1 month of standard chemotherapy in the metastatic setting and still be eligible to initiate protocol therapy in the first-line setting. Adjuvant or neoadjuvant therapy does not count as a line of therapy even if given in the setting of metastatic disease (oligometastatic), unless disease recurrence was noted within 6 months of completing the last dose of the adjuvant or neoadjuvant therapy.
• For Cohort B: Participants must have had at least stable disease (per treating physician) on a prior EGFR inhibitor containing regimen and it must be at least 4 months since the prior anti-EGFR inhibitor treatment was completed. Participants previously enrolled in Cohort A can later enroll in Cohort B should the eligibility criteria be met.
• For Cohort C: Subjects with no prior use of irinotecan or anti-EGFRi. If patients were treated on cohort A (of this study) they can cross-over to cohort C if other eligibility criteria are met at the time of cross-over.
• Evaluable disease according to RECIST v1.1. Participants do not have to have measureable disease.
• Participants with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic.
• Demonstrate adequate organ function; all screening labs to be obtained within 7 days prior to registration. Note minimum platelet requirement differs between Cohort A and B.
• Absolute Neutrophil Count (ANC) ≥ 1,000 / mcL
• Platelets ≥ 50,000 / mcL (Cohort A); ≥ 50,000 mcL (Cohort B receiving only EGFRi); ≥75,000 / mcL (cohort B receiving irinotecan and EGFRi; and cohort C)
• Serum creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ 2.0 X upper limit of normal (ULN) OR ≥ 60 mL/min for subject with creatinine levels \> 2.0 X institutional ULN
• Bilirubin ≤ 1.5 × ULN OR direct bilirubin ≤ ULN for subjects with bilirubin levels \>1.5 x ULN
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 5 × ULN

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Doris Duke Charitable Foundation: collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Panitumumab; Cetuximab; Irinotecan; IFL protocol; Bevacizumab

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; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Dustin Deming, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is an open label phase 2 clinical trial with 3 independent study arms conducted through the University of Wisconsin Carbone Cancer Center

Study Record Dates

• First Submitted: October 8, 2020
• First Posted: October 14, 2020
• Study Start: October 19, 2020
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: February 5, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)