Anti-EGFR Therapy for the Treatment of Select Patients with Metastatic Colorectal Cancer
- 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
- 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
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.
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.
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
University of Wisconsin Hospital and Clinics
Dustin Alan Deming
- Primary ID UW20038
- Secondary IDs NCI-2020-06543, 2020-0714
- Clinicaltrials.gov ID NCT04587128