Clinical Trials /

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

NCT04587128

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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 7/23/2020
  • SECONDARY ID: 2020-0714
  • SECONDARY ID: NCI-2020-06543
  • NCT ID: NCT04587128

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
PanitumumabCohort A: No Previous EGFR
CetuximabCohort A: No Previous EGFR
IrinotecanCohort 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

NameTypeDescriptionInterventions
Cohort A: No Previous EGFRExperimentalParticipant 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
  • Panitumumab
  • Cetuximab
Cohort B: RetreatmentExperimentalParticipants 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.

          -  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:Not yet recruiting
Lead Sponsor:University of Wisconsin, Madison

Last Updated

October 8, 2020