A Single Arm Phase II Study to Evaluate Treatment With Gevokizumab in Patients With Stage II/III Colon Cancer Who Are ctDNA-positive After Curative Surgery and Adjuvant Chemotherapy

NCT05178576 | Withdrawn Phase 2 FDA Drug FDA Device

• 1 other identifier: NSABP FC-12
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

Brief Summary

This study will look at the recurrence-free survival of microsatellite-stable (MSS) colon cancer in patients are ctDNA (circulating tumor DNA) positive and treated with gevokizumab.

Conditions

Colon Cancer

Keywords

ctDNA positive; adjuvant; Signatera; gevokizumab; chemotherapy; Stage II; Stage III; Microsatellite Stable (MSS)

Outcome Measures

Primary Outcomes (1)

• Recurrence-free survival (RFS) at one year

  Percentage of patients alive absent recurrence

  From the initiation of study therapy through 1 year of follow-up

Secondary Outcomes (6)

• Clearance of ctDNA

  From the initiation of study therapy to 8 weeks

• Duration of Recurrence-free survival (RFS) with ctDNA clearance at 8 weeks from start of study therapy

  From the initiation of study therapy through 1 year of follow-up

• Duration of Recurrence-free survival (RFS) without ctDNA clearance at 8 weeks

  From the initiation of study therapy through 1 year of follow-up

• Frequency of adverse events assessed using CTCAE 5.0

  From beginning of study therapy until 90 days after last dose, approximately 15 months

• Serum concentration

  From beginning of study therapy until 30 days after last dose

Study Arms (1)

Arm 1

EXPERIMENTAL

ctDNA positive Gevokizumab for 1 year (maximum of 13 cycles)

Drug: Gevokizumab; Diagnostic Test: Signatera test

Interventions

Gevokizumab DRUG

120mg IV on day 1 of every 28-day cycle for 1 year (maximum of 13 cycles)

Arm 1

Signatera test DIAGNOSTIC_TEST

ctDNA monitoring at weeks 8, 12, 24, 36, 48, 60 and 72 unless disease recurrence is documented.

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The ECOG performance status must be 0 or 1.
• Patients must have histologically/pathologically confirmed stage II/III adenocarcinoma of the colon (per AJCC 8th edition) with R0 resection by open laparotomy or laparoscopic-assisted colectomy.
• There must be documentation by CT scan with contrast that the patient has no evidence of measurable metastatic disease including assessment of chest, abdomen, and pelvis. (Note: MRI will be accepted for patients unable to have CT scans with contrast.)
• Patients must have completed at least 3 months of a standard adjuvant chemotherapy regimen.
• The distal extent of the tumor must be greater than or equal to 12 cm from the anal verge on colonoscopy or above the peritoneal reflection as documented during surgery or on pathology specimen.
• Patients with microsatellite stable (MSS) proficient mismatch repair (pMMR) tumors are eligible.
• Patients must be ctDNA-positive as determined by the Natera Signatera™ assay from samples submitted to Natera within less than or equal to 6 weeks after completing adjuvant chemotherapy. The study will provide pre-entry ctDNA testing for consenting stage III patients. Note: Stage II colon cancer patients may be ctDNA tested via the FC-12 study provided all the following criteria are met:
• The patient must have been previously determined to be ctDNA-positive by Natera's Signatera™ commercial assay outside of the study (i.e., at the time of resection).
• The patient has received at least 3 months of a standard chemotherapy regimen.
• Patients must sign the FC-12 ctDNA Screening consent and samples must be submitted to Natera within less than or equal to 6 weeks after completion of the adjuvant chemotherapy for reconfirmation of ctDNA-positivity by the Signatera™ assay via the FC-12 study.
• Patients must be able to begin study therapy within 14 weeks after the completion of adjuvant chemotherapy.
• At the time of study entry, blood counts performed within 2 weeks prior to study entry must meet the following criteria:
• ANC must be greater than or equal to 1500/mm3,
• Platelet count must be greater than or equal to 100,000/mm3; and
• Hemoglobin must be greater than or equal to 9 g/dL. (Note: transfusions maybe used to correct hemoglobin for patients experiencing anemia from therapy who otherwise would be eligible for the study.)

You may not qualify if:

• Diagnosis of anal or small bowel carcinoma.
• Colon cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.
• Patients with MSI-high defective mismatch repair (dMMR) tumors are ineligible.
• An elevated CEA above institutional normal value. For smokers a higher institution ULN is acceptable.
• Use and/or receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, targeted therapy, biologic therapy, monoclonal anti-bodies) or radiation therapy within 4 weeks prior to receiving first dose of study therapy.
• Persistent diarrhea greater than grade 1.
• History of active or latent tuberculosis (TB) infection. If presence of TB (active or latent) is established, then treatment for TB must be completed according to local guidelines prior to the screening.
• Active untreated or uncontrolled systemic fungal, bacterial or viral infections, or active infection requiring systemic anti-infectious therapy.
• Patients will be excluded if they are on systemic steroid therapy that cannot be discontinued (except for the use of prednisone or equivalent less than 0.125mg/kg/day as replacement therapy). Inhaled or topical steroids are permitted.
• Receipt of live attenuated vaccination within 30 days prior to study entry.
• Active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCB) infections.
• Note: Patients with a history of hepatitis C virus (HCV) infection must have been treated and with confirmation of cure, can be eligible.
• Active infection or chronic infection requiring chronic suppressive antibiotics.
• History of allogeneic organ or bone marrow transplantation.
• Any of the following cardiac conditions:

Sponsors & Collaborators

• NSABP Foundation Inc: lead
• Novartis Pharmaceuticals: collaborator
• Natera, Inc.: collaborator

Study Sites (5)

UF Health Davis Cancer Pavilion and Shands Med Plaza

Gainesville, Florida, 32608, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

AHN Cancer Institute

Pittsburgh, Pennsylvania, 15212, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

gevokizumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Norman Wolmark, MD

  NSABP Foundation Inc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: January 5, 2022
• Study Start: June 24, 2022
• Primary Completion: February 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: November 4, 2022

Record last verified: 2022-11

Locations

US (5)