Description:
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 110 participants with left-sided, unresectable metastatic CRC. Participants will be on
study up to 5 years.
Title
- Brief Title: Early-Line Anti-EGFR Therapy to Facilitate Retreatment for Select Patients With mCRC
- Official Title: Phase II Trial of Early-Line Anti-EGFR Therapy to Facilitate Retreatment for Select Patients With Metastatic Colorectal Cancer
Clinical Trial IDs
- ORG STUDY ID:
UW20038
- SECONDARY ID:
A534260
- SECONDARY ID:
SMPH/MEDICINE/HEM-ONC
- SECONDARY ID:
Protocol Version 3/8/2021
- SECONDARY ID:
2020-0714
- SECONDARY ID:
NCI-2020-06543
- NCT ID:
NCT04587128
Conditions
- Metastatic Colorectal Cancer
Interventions
Drug | Synonyms | Arms |
---|
Panitumumab | | Cohort A: No Previous EGFR |
Cetuximab | | Cohort A: No Previous EGFR |
Irinotecan | | Cohort B: Retreatment |
Purpose
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 110 participants with left-sided, unresectable metastatic CRC. Participants will be on
study up to 5 years.
Trial Arms
Name | Type | Description | Interventions |
---|
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 | |
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 | - Panitumumab
- Cetuximab
- Irinotecan
|
Eligibility Criteria
Inclusion Criteria:
- 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 of neoadjuvant therapy.
- For Cohort B: Participants 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. Participants
previously enrolled in Cohort A can later enroll in Cohort B should the
eligibility criteria be met.
- 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); ≥ 75,000 mcL (Cohort B)
- 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
- Albumin ≥ 2.5 mg/dL
- Females of childbearing potential must have a negative serum pregnancy test within 7
days of registration and not be breastfeeding. 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 (MSI) testing must be MSI-stable or MSI-low.
- Or 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.
- Participants must not have known additional malignancy that is requiring systemic
treatment. Participants taking hormonal treatments for breast or prostate cancer are
still eligible.
- 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.
- Participants must have no metastatic cancer lesions greater than 3.5cm in diameter.
Any number of metastatic lesions will be allowed.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Cohort A Objective Response Rate (ORR) |
Time Frame: | up to 1 year |
Safety Issue: | |
Description: | Objective responses which will include all confirmed complete responses (CR) and confirmed partial responses (PR) determined as per RECIST v1.1 on treatment with panitumumab in metastatic, left-sided, non-bulky colorectal cancer. |
Secondary Outcome Measures
Measure: | Cohort A Progression Free Survival (PFS) |
Time Frame: | up to 4 years |
Safety Issue: | |
Description: | 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. |
Measure: | Cohort B Objective Response Rate (ORR) |
Time Frame: | up to 1 year |
Safety Issue: | |
Description: | Objective responses which will include all confirmed complete responses (CR) and confirmed partial responses (PR) determined as per RECIST v1.1 on treatment with panitumumab in metastatic, left-sided, non-bulky colorectal cancer. |
Measure: | Type and Severity of Toxicities |
Time Frame: | up to 1 year (adverse events collected to 30 days post treatment) |
Safety Issue: | |
Description: | Toxicities will be graded using the most recent version of the CTCAE criteria. Toxicities will be summarized by type and severity in tabulator format. |
Measure: | Rate of Retreatment with EGFRi |
Time Frame: | up to 4 years |
Safety Issue: | |
Description: | The rate of retreatment with EGFRi will be defined as the proportions of all eligible subjects who are retreated with EGFRi among all eligible subjects. |
Measure: | Overall Survival (OS) |
Time Frame: | up to 4 years |
Safety Issue: | |
Description: | OS will be defined as the duration (in months) from the date of study enrollment to the date of death (of any case). If no death event is observed during the follow-up period in a subject, then OS for that subject will be censored at the date of the last known survival status. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | University of Wisconsin, Madison |
Last Updated
June 22, 2021