We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04587128
Recruitment Status : Recruiting
First Posted : October 14, 2020
Last Update Posted : September 15, 2022
Sponsor:
Collaborator:
Doris Duke Charitable Foundation
Information provided by (Responsible Party):
University of Wisconsin, Madison

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 110 participants with left-sided, unresectable metastatic CRC. Participants will be on study up to 5 years.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: Panitumumab Drug: Cetuximab Drug: Irinotecan Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study is an open label phase 2 clinical trial with 2 independent study arms conducted through the University of Wisconsin Carbone Cancer Center
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Early-Line Anti-EGFR Therapy to Facilitate Retreatment for Select Patients With Metastatic Colorectal Cancer
Actual Study Start Date : October 19, 2020
Estimated Primary Completion Date : October 2025
Estimated Study Completion Date : October 2025

Arm Intervention/treatment
Experimental: Cohort A: No Previous EGFR

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
Epidermal growth factor receptor inhibitor, anti-neoplastic

Drug: Cetuximab
Epidermal growth factor receptor inhibitor, anti-neoplastic

Experimental: Cohort B: Retreatment

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
Epidermal growth factor receptor inhibitor, anti-neoplastic

Drug: Cetuximab
Epidermal growth factor receptor inhibitor, anti-neoplastic

Drug: Irinotecan
anti-neoplastic, chemotherapy drug




Primary Outcome Measures :
  1. Cohort A Objective Response Rate (ORR) [ Time Frame: up to 1 year ]
    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.

  2. Cohort B Progression Free Survival (PFS) [ Time Frame: up to 4 years ]
    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.


Secondary Outcome Measures :
  1. Cohort A Progression Free Survival (PFS) [ Time Frame: up to 4 years ]
    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.

  2. Cohort B Objective Response Rate (ORR) [ Time Frame: up to 1 year ]
    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.

  3. Type and Severity of Toxicities [ Time Frame: up to 1 year (adverse events collected to 30 days post treatment) ]
    Toxicities will be graded using the most recent version of the CTCAE criteria. Toxicities will be summarized by type and severity in tabulator format.

  4. Rate of Retreatment with EGFRi [ Time Frame: up to 4 years ]
    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.

  5. Overall Survival (OS) [ Time Frame: up to 4 years ]
    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.


Other Outcome Measures:
  1. Change in Participant Derived Organotypic Spheroid Response over baseline [ Time Frame: baseline, post treatment (up to 1 year) ]
    To determine the ability of patient-derived colorectal cancer organoids to predict clinical response to EGFR inhibition, participant derived organotypic spheroids will be grown from biopsy at baseline assessment and compared to clinical response from EGFR inhibitor. This measure will a percentage change from the baseline.

  2. Circulating Tumor DNA (ctDNA) at time of Progression [ Time Frame: 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) ]
    To evaluate ctDNA for early markers predictive of clinical resistance, ctDNA will be evaluated for subclonal alterations at the time of clinical disease progression and compared to repeat tissue biopsy.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 receiving irinotecan and EGFRi); ≥ 50,000 / mcL (Cohort B receiving only EGFRi)
    • 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 (Cohort A); Tumor molecular profiling from prior to anti-EGFR therapy with no pathologic variants in KRAS or NRAS or BRAF V600 mutations. If additional molecular profiling is completed (tissue or blood based testing) after receiving cetuximab or panitumumab treatment and variants in KRAS or NRAS are found, those patients will be considered eligible for this study. Patients with BRAF V600 mutations are not eligible. (Cohort B)
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04587128


Contacts
Layout table for location contacts
Contact: Cancer Connect 800-622-8922 clinicaltrials@cancer.wisc.edu

Locations
Layout table for location information
United States, Wisconsin
University of Wisconsin Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53792
Contact: Cancer Connect    800-622-8922    clinicaltrials@cancer.wisc.edu   
Principal Investigator: Dustin Deming, MD         
Sponsors and Collaborators
University of Wisconsin, Madison
Doris Duke Charitable Foundation
Investigators
Layout table for investigator information
Principal Investigator: Dustin Deming, MD University of Wisconsin, Madison
Layout table for additonal information
Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT04587128    
Other Study ID Numbers: UW20038
A534260 ( Other Identifier: UW Madison )
SMPH/MEDICINE/HEM-ONC ( Other Identifier: UW Madison )
Protocol Version 3/8/2021 ( Other Identifier: UW Madison )
2020-0714 ( Registry Identifier: Health Science IRB )
NCI-2020-06543 ( Registry Identifier: NCI Trial ID )
First Posted: October 14, 2020    Key Record Dates
Last Update Posted: September 15, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Cetuximab
Panitumumab
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological