RECRUITING

Phase II Open-label Trial of Neoadjuvant Immunochemotherapy for Resectable Non-metastatic Colon cancER: NICER

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Conditions

Stage I Colon CancerStage II Colon CancerStage III Colon CancerNon-metastatic resectable colon cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a Phase II open-label trial of neoadjuvant immunochemotherapy with Atezolizumab and CAPOX followed by surgery and potentially adjuvant chemotherapy for patients with localized resectable pMMR adenocarcinoma of the colon with a target accrual of 28 patients. The investigators will explore if appropriately timed neoadjuvant CAPOX with anti-PD-L1 mAb (Atezolizumab) can be administered safely and feasibly, and that this combination will lead to improved clinical response associated with enhanced numbers of immune cells in surgically resected colon tumors. Patients will receive 4 cycles of atezolizumab in combination with 4 cycles of CAPOX (atezolizumab will be administered prior to chemotherapy) before standard of care surgical resection. Following surgery, patients still considered to be at high-risk of recurrence (per SOC guidelines) will receive further adjuvant chemotherapy (mFOLFOX6 or CAPOX), based on the discretion of the treating oncologist/investigator. Circulating tumor DNA (ctDNA) dynamic change status will be analyzed through collection of blood samples throughout different stages of the patient's neoadjuvant treatment regimen (baseline, pre-neoadjuvant therapy, mid-neoadjuvant, post-neoadjuvant therapy, and during postoperative period) as a marker of early read on efficacy. The end of the study for each patient enrolled will be at the 6 month postoperative visit. On Study Protocol: Patients will be followed up for an efficacy follow-up phase during the first 6 months after surgery (week 2 \& months 3, 6 visits). All assessments beyond the 6 month visit will be performed under standard of care surveillance office visits. Off Study Protocol: Thereafter they will enter a survival follow-up phase per standard of care protocols. Patients will be seen every 6 months starting at month 12 until month 36. All collection of research-specific assessments including whole blood, stool collection and quality of life questionnaires will be optional beyond the 6 month postop visit (months 12-36).

Official Title

Phase II Open-label Trial of Neoadjuvant Immunotherapy (Atezolizumab) in Combination With CAPOX for Resectable Non-metastatic Proficient Mismatch Repair (pMMR) Colon CancER: NICER Study

Quick Facts

Study Start:2025-02-01
Study Completion:2028-01-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05870800

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 80 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Signed Informed Consent Form
  2. * Age \>18 years at time of signing Informed Consent Form
  3. * Ability to comply with the study protocol
  4. * MSS or pMMR tumor determined by local CLIA-certified PCR or IHC testing respectively.
  5. * Histologically or cytologically confirmed resectable non-metastatic adenocarcinoma of the colon (stages I-III)
  6. * The distal extent of the tumor must be ≥12 cm from the anal verge on pre-surgical endoscopy and/or imaging (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation). If the patient did not undergo a pre-surgical endoscopy, then the distal extent of the tumor must be ≥12 cm from the anal verge as determined by surgical examination or pre-operative imaging.
  7. * Availability of a representative tumor specimen (preop biopsy or surgical tissue specimen) for ctDNA assay design from tumor sample and for exploratory biomarker research determination.
  8. * One or more of the following high-risk features:
  9. * High CEA levels (\>5 ng/ml in non-smoker patients , \>10ng/ml in smoker patients)
  10. * Low Lymphocyte-to-monocyte Ratio (\<2.38)
  11. * Poor grade of tumor differentiation
  12. * Evidence of Lymphovascular Invasion
  13. * Evidence of Perineural Invasion
  14. * CT evidence of T3 orT4 disease w/ ≥4 cm tumor longitudinal diameter
  15. * CT evidence of regional lymphadenopathy
  16. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
  17. * Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
  18. * ANC ≥ 1.5 x 10\*9/L (1500/mL) without granulocyte colony-stimulating factor support
  19. * Lymphocyte count ≥ 0.5 x 10\*9/L (500/µL)
  20. * Platelet count ≥100 x 10\*9/L (100,000/µL) without transfusion
  21. * Hemoglobin ≥ 9 g/L (9 g/dL) Patients may be transfused to meet this criterion.
  22. * AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN)
  23. * Serum bilirubin ≤ 1.5 x ULN with the following exception:
  24. * Serum creatinine ≤1.5 x ULN or Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula)
  25. * Serum albumin ≥ 25 g/L (2.5 g/dL)
  26. * For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
  27. * For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
  28. * Negative hepatitis B surface antigen (HBsAg) test at screening
  29. * Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening The HCV RNA test must be performed for patients who have a positive HCV antibody test.
  30. * Negative HIV test at screening
  31. * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
  1. * Symptomatic, untreated, or any site actively progressing metastatic disease.
  2. * History of leptomeningeal disease
  3. * Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable regimen at study entry. Presence of any metastatic effusion (pleural, pericardial, ascites)
  4. * Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
  5. * Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis (see Appendix 11 for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions:
  6. * Rash must cover \< 10% of body surface area
  7. * Disease is well controlled at baseline and requires only low-potency topical corticosteroids
  8. * There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
  9. * History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  10. * Active tuberculosis
  11. * Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  12. * Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
  13. * History of malignancy other than colon adenocarcinoma within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, Stage I uterine cancer or colonic polyps
  14. * Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could impact patient safety
  15. * Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
  16. * Prior allogeneic stem cell or solid organ transplantation
  17. * Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
  18. * Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
  19. * Current treatment with anti-viral therapy for HBV
  20. * Synchronous primary rectal and/ or colon cancers or history of prior invasive colon malignancy, regardless of disease-free interval.
  21. * Treatment with investigational therapy within 28 days prior to initiation of study treatment
  22. * Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  23. * Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
  24. * Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF- agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
  25. * History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
  26. * Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
  27. * Known allergy or hypersensitivity to any component of the CAPEOX or mFOLFOX6 chemotherapy formulations
  28. * Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months for Atezolizumab and 6 months for any chemotherapy regimen after the final dose of study treatment Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.

Contacts and Locations

Study Contact

Hector J Garcia-Chavez, MD
CONTACT
713-798-6419
hector.garcia-chavez@bcm.edu

Principal Investigator

Atif Iqbal, MD
PRINCIPAL_INVESTIGATOR
Baylor College of Medicine

Study Locations (Sites)

Baylor College of Medicine
Houston, Texas, 77030
United States

Collaborators and Investigators

Sponsor: Baylor College of Medicine

  • Atif Iqbal, MD, PRINCIPAL_INVESTIGATOR, Baylor College of Medicine

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-02-01
Study Completion Date2028-01-01

Study Record Updates

Study Start Date2025-02-01
Study Completion Date2028-01-01

Terms related to this study

Keywords Provided by Researchers

  • Non-metastatic resectable colon cancer

Additional Relevant MeSH Terms

  • Stage I Colon Cancer
  • Stage II Colon Cancer
  • Stage III Colon Cancer