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

NCT05870800 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: H-52907
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Stage I Colon Cancer; Stage II Colon Cancer; Stage III Colon Cancer

Keywords

Non-metastatic resectable colon cancer

Outcome Measures

Primary Outcomes (1)

• Determine the rate of tumor regression grade 1 (<10% viable cancer cells) to neoadjuvant immunotherapy and chemotherapy in resectable (non-metastatic) pMMR colon cancer, assessed in the resection specimen.

  The primary outcome will be evaluated using the modified Ryan scoring system to score tumor regression grades (TRGs) in the surgical specimen. Scores will be assessed by dedicated study pathologists. Success is defined as TRG-0 or TRG-1(\<10% viable cancer cells). Efficacy-evaluable participants who do not go to surgery, perhaps due to clinical progression, will be counted as a failure.

  3-5 months

Secondary Outcomes (11)

• Complete pathologic response (TRG-0) to neoadjuvant immunochemotherapy or not.

  36 months

• R0 resection and number of lymph nodes harvested after neoadjuvant combination CAPOX / Atezolizumab

  3-4 months

• Utilize dynamic changes in ctDNA as an early assessment tool on therapy efficacy. Analysis of ctDNA status to evaluate incidence and changes in surrogate ctDNA biomarker presence.

  36 months

• Occurrence of any grade 3 or greater adverse events possibly, probably or definitively related to the neoadjuvant CAPOX / Atezolizumab combination

  3-12 months

• Quality of life as assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)

  36 months

Study Arms (1)

Neoadjuvant Therapy Arm

EXPERIMENTAL

Subjects will receive 4 cycles of neoadjuvant atezolizumab in combination with 4 cycles of CAPOX before standard of care surgical resection. After surgery, patients who are still considered high risk for recurrence (per the treating medical oncologist) will be offered adjuvant therapy.

Drug: Tecentriq 1200 MG in 20 ML Injection + Capecitabine 1000 mg/m2 + Oxaliplatin 130 mg/m2; Drug: Oxaliplatin injection 85mg/m2 + Leucovorin 400mg/m2 + 5-Fluorouracil 2400mg/m2; Drug: Oxaliplatin 130mg/m2 + Capecitabine 1000mg/m2

Interventions

Tecentriq 1200 MG in 20 ML Injection + Capecitabine 1000 mg/m2 + Oxaliplatin 130 mg/m2 DRUG

Enrolled Participant will receive 4 cycles of neoadjuvant Atezolizumab (Tecentriq) followed by CAPOX chemotherapy prior to surgery. Each cycle is every 3 weeks. (12 weeks)

Also known as: Neoadjuvant Chemoimmunotherapy

Neoadjuvant Therapy Arm

Oxaliplatin injection 85mg/m2 + Leucovorin 400mg/m2 + 5-Fluorouracil 2400mg/m2 DRUG

After Surgery, if patients are still considered at high risk (per treating investigator) subjects will be eligible to receive adjuvant chemotherapy with mFOLFOX6 Q2 weeks x 6 cycles (12 weeks) or CAPOX Q3 weeks x 4 cycles (12 weeks)

Also known as: mFOLFOX6

Neoadjuvant Therapy Arm

Oxaliplatin 130mg/m2 + Capecitabine 1000mg/m2 DRUG

After Surgery, if patients are still considered at high risk (per treating investigator) subjects will be eligible to receive adjuvant chemotherapy with mFOLFOX6 Q2 weeks x 6 cycles (12 weeks) or CAPOX Q3 weeks x 4 cycles (12 weeks)

Also known as: CAPOX

Neoadjuvant Therapy Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form
• Age ≥18 years at time of signing Informed Consent Form
• Ability to comply with the study protocol
• MSS or pMMR tumor determined by local CLIA-certified PCR or IHC testing respectively.
• Histologically or cytologically confirmed resectable non-metastatic adenocarcinoma of the colon.
• 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.
• One or more of the following high-risk features:
• High CEA levels (\>5 ng/ml in non-smoker patients , \>10ng/ml in smoker patients)
• Low Lymphocyte-to-monocyte Ratio (\<2.38)
• Poor grade of tumor differentiation
• Evidence of Lymphovascular Invasion
• Evidence of Perineural Invasion
• CT evidence of T3 orT4 disease w/ ≥4 cm tumor longitudinal diameter
• CT evidence of regional lymphadenopathy
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

You may not qualify if:

• Symptomatic, untreated, or any site actively progressing metastatic disease.
• History of leptomeningeal disease
• 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)
• Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
• 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:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover \< 10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids
• 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
• 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.
• Active tuberculosis
• 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
• 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

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

atezolizumab; Injections; Capecitabine; Oxaliplatin; Leucovorin; Fluorouracil

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

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Atif Iqbal, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hector J Garcia-Chavez, MD

CONTACT

713-798-6419; hector.garcia-chavez@bcm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Phase II open-label trial of neoadjuvant CAPOX chemotherapy with Atezolizumab followed by surgery for patients with localized resectable pMMR adenocarcinoma of the colon

Study Record Dates

• First Submitted: April 11, 2023
• First Posted: May 23, 2023
• Study Start: June 15, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): January 1, 2028
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)