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Anti-EGFR Therapy for the Treatment of Select Patients with Metastatic Colorectal Cancer

Trial Status: Active

This phase II trial investigates how well the anti-EGFR drugs cetuximab or panitumumab work alone or in combination with irinotecan in treating patients with colorectal cancer that has spread to other places in the body (metastatic). Cetuximab and panitumumab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread. Irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cetuximab or panitumumab alone or in combination with irinotecan may stop or slow colorectal cancer.

Inclusion Criteria

  • Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately
  • As determined by the enrolling physician or protocol designee, ability of the subject 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: Subjects must enroll for study treatment in the first or second-line metastatic setting. Subjects 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 of neoadjuvant therapy * For Cohort B: Subjects must have had at least stable disease (per treatment 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. Patients previously enrolled in Cohort A can later enroll in Cohort B should the eligibility criteria be met
  • Evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Subjects do not have to have measurable disease
  • A subject 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
  • Absolute neutrophil count (ANC) >= 1,000 /mcL (obtained within 7 days prior to registration)
  • Platelets >= 75,000 / mcL (obtained within 7 days prior to registration)
  • Serum creatinine =< 2.0 X upper limit of normal (ULN) OR measured or calculated creatinine clearance >= 60 mL/min for subject with creatinine levels > 2.0 X institutional ULN (obtained within 7 days prior to registration) (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) * Creatinine clearance should be calculated per institutional standard
  • Bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with bilirubin levels > 1.5 X ULN (obtained within 7 days prior to registration)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 X ULN (obtained within 7 days prior to registration)
  • Albumin >= 2.5 mg/dL (obtained within 7 days prior to registration)
  • Females of childbearing potential must have a negative serum pregnancy test within 7 days of registration and not be breastfeeding. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
  • Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 120 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method
  • Tumor must be mismatch repair (MMR) proficient as determined by microsatellite instability or immunohistochemistry for MMR proteins * Microsatellite instability testing must be MSI-stable or MSI-low * Or immunohistochemistry (IHC) for MMR proteins must demonstrate intact MMR proteins
  • Standard tumor molecular profiling with no pathologic variants in KRAS or NRAS or BRAF V600 mutations
  • No major surgery within prior 2 weeks of treatment initiation
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to panitumumab or cetuximab, including known severe hypersensitivity reactions to monoclonal antibodies

Exclusion Criteria

  • Subjects must not have known additional malignancy that is requiring systemic treatment. Subjects taking hormonal treatments for breast or prostate cancer are still eligible
  • Subjects must have no metastatic cancer lesions greater than 3.5cm in diameter. Any number of metastatic lesions will be allowed

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: ACTIVE
Contact: Dustin Alan Deming
Phone: 608-265-1700

PRIMARY OBJECTIVE:

I. To estimate the objective response rate (ORR) of anti-EGFR monotherapy in the early-line setting for patients with untreated metastatic colorectal cancer with left-sided, non-bulky disease and assess progression free survival of retreatment in the late-line setting.

SECONDARY OBJECTIVES:

I. To evaluate progression free survival (PFS), and overall survival (OS) in subjects receiving anti-EGFR monotherapy in the early-line setting and in the late-line setting.

II. To determine the toxicity profile of single agent panitumumab or cetuximab in the early-line setting.

III. To examine the proportion of patients eligible for retreatment with EGFR inhibitors and the ORR/PFS/OFS for patients who undergo EGFR inhibitor retreatment.

CORRELATIVE/EXPLORATORY OBJECTIVES:

I. To determine the ability of patient-derived colorectal cancer organoids to predict clinical response to EGFR inhibition.

II. To evaluate circulating tumor-deoxyribonucleic acid (ctDNA) for early markers predictive of clinical resistance.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT A: Patients receive panitumumab intravenously (IV) over 60-90 minutes on days or cetuximab IV over 60-120 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

COHORT B: Patients receive panitumumab IV over 60-90 minutes or cetuximab IV over 60-120 minutes on days 1 and 15. Patients may also receive irinotecan IV over 90 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 6 months for 4 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Wisconsin Hospital and Clinics

Principal Investigator
Dustin Alan Deming

  • Primary ID UW20038
  • Secondary IDs NCI-2020-06543, 2020-0714
  • Clinicaltrials.gov ID NCT04587128