Overview

Eligibility

Design Details

Arms & Interventions

Outcome Measures

Trial Sites

Source: NCT05870800

Recruiting

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

Interventional

Phase 2

Baylor College of Medicine

Sponsor: Baylor College of Medicine

Last Updated: May 25, 2025
Notice- Information is sourced from public registries and may not reflect real-time changes at the local site.

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).

Show Detailed Description

Treatment Category

Chemotherapy

Required Mutations

None

Trial Started

June 15, 2025

Last Updated by Sponsor

May 25, 2025

Estimated Completion

September 1, 2026

Contact Study

Name:Hector J Garcia-Chavez, MD

Email:hector.garcia-chavez@bcm.edu

Phone:713-798-6419

Eligibility

Inclusion Criteria

* 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

* Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:

* ANC ≥ 1.5 x 10*9/L (1500/mL) without granulocyte colony-stimulating factor support

* Lymphocyte count ≥ 0.5 x 10*9/L (500/µL)

* Platelet count ≥100 x 10*9/L (100,000/µL) without transfusion

* Hemoglobin ≥ 9 g/L (9 g/dL) Patients may be transfused to meet this criterion.

* AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN)

* Serum bilirubin ≤ 1.5 x ULN with the following exception:

Patients with known Gilbert disease: serum bilirubin ≤ 3 x ULN

* Serum creatinine ≤1.5 x ULN or Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula)

* Serum albumin ≥ 25 g/L (2.5 g/dL)

* For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN

* For patients receiving therapeutic anticoagulation: stable anticoagulant regimen

* Negative hepatitis B surface antigen (HBsAg) test at screening

* 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.

* Negative HIV test at screening

* 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:

Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the final dose of atezolizumab and for 6 months following any of the adjuvant chemotherapy regimens (if applicable) after the final dose of mFOLFOX6 or CAPEOX.Women must refrain from donating eggs during this same period.

A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries, fallopian tubes and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a woman with a tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.

Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.

The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.

• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below: With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for 5 months after the final dose of any chemotherapy regimen. Men must refrain from donating sperm during this same period.

With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 5 months after any of the chemotherapy regimens to avoid exposing the embryo.

Exclusion Criteria

* 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

* 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

* 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

* 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.

* Prior allogeneic stem cell or solid organ transplantation

* 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

* 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

* Current treatment with anti-viral therapy for HBV

* Synchronous primary rectal and/ or colon cancers or history of prior invasive colon malignancy, regardless of disease-free interval.

* Treatment with investigational therapy within 28 days prior to initiation of study treatment

* Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies

* 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

* 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:

Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.

Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.

* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins

* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation

* Known allergy or hypersensitivity to any component of the CAPOX or mFOLFOX6 chemotherapy formulations

* 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.

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Design Details

AllocationN/A

Intervention ModelSingle Group Assignment

MaskingNone (Open Label)

Number to Enroll28

Arms & Interventions

Arms

Interventions

Type: Experimental

Description: 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.

Interventions:

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

Outcome Measures

Primary Outcome Measures

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.3-5 months

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.

Secondary Outcome Measures

Complete pathologic response (TRG-0) to neoadjuvant immunochemotherapy or not.36 months

The investigators will estimate the rate of tumor regression grade (TRG) 0/1 and corresponding exact 95% confidence interval (Wilson method) in the 'efficacy' population. The rate will be compared to the null value of 1% using an exact binomial test with a 5% one-sided significance level. With N=25 efficacy evaluable participants, the investigators will need to see at least 2 grade 0/1 tumor regressions in order to reject the null hypothesis.

R0 resection and number of lymph nodes harvested after neoadjuvant combination CAPOX / Atezolizumab3-4 months

R0 resection rate will be summarized as described for the primary endpoint.

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

CtDNA dynamic changes as an early assessment on efficacy. Analysis of ctDNA status (pre-neoadjuvant therapy, mid-neoadjuvant therapy, post- neoadjuvant therapy and postoperative) correlating ctDNA with outcomes and to evaluate incidence and changes in surrogate ctDNA biomarker presence.

Occurrence of any grade 3 or greater adverse events possibly, probably or definitively related to the neoadjuvant CAPOX / Atezolizumab combination3-12 months

This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0 for toxicity and Serious Adverse Event reporting, with the exception of skin- or nail-related toxicities, which will be graded using CTCAE version 5.0 with modifications. Treatment emergent AE's (grade 3 or greater), will be tabulated with counts of AE's at each grade, as well as counts of participants experiencing any grade 3 or greater treatment emergent AE.

Quality of life as assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)36 months

QoL scores and patient satisfaction results will be computed using standard guidelines and displayed graphically as spaghetti plots. QLQ-C30 scores range from 0 to 100, with higher scores indicating higher/better functioning and higher/better global health status/QoL but lower/worse symptom burden.

Quality of life as assessed by MD Anderson Symptom Inventory (MDASI)36 months

QoL scores and patient satisfaction results will be computed using standard guidelines and displayed graphically as spaghetti plots. The M. D. Anderson Symptom Inventory (MDASI) is a brief, patient-reported outcome measure of the impact and severity of 13 cancer-related symptoms that are common across all cancer types. The MDASI score goes from 0 (symptom has not been present) to 10 (the symptom is as worse as it could be) for each item. Higher score means worse outcome.

Delay in surgery after neoadjuvant therapy by more than 12 weeks (84 days) or no3-24 months

Complete surgical resection rates (R0) will be monitored in these patients and if the R0 resection rate is numerically lower than the historical average of ~73% noted in the literature, further analysis of these cases would be performed to ensure that this was not attributed to the delay caused by neoadjuvant therapy.

Rate of treatment acceptance measured by a patient satisfaction questionnaire (PSQ) result at specified time points.6-12 months

An in-house patient satisfaction questionnaire (PSQ) results will be computed using standard guidelines and displayed graphically as spaghetti plots. The patient satisfaction questionnaire is a brief, in house, patient satisfaction questionnaire to assess the rate of patient satisfaction, tolerance and acceptance of neoadjuvant treatment used during the study. It includes a brief 10-question assessment and score goes from 0 (not satisfied at all) to 10 (very satisfied).

Overall Survival (OS)- Post-surgery times to event36 months

Post-surgery times to event (OS) will be measured in months throughout the duration of the study (36 months). Overall survival (OS) is the time from surgery to death from any cause, regardless of disease recurrence (safety population). OS will be summarized by Kaplan-Meier curves, with estimates of median time to event (95% CI by log-log transform), and selected time-specific survival rates (95% CI).

Relapse-free survival (RFS)- Post-surgery times to event36 months

Post-surgery times to event (RFS) will be measured in months throughout the duration of the study (36 months). Relapse-free survival (RFS) is defined as the time from surgery to any event, where an "event" is defined first radiographical or pathological evidence of recurrence of disease (excluding second primary cancers) or death from any cause, whichever comes first. RFS will be summarized by Kaplan-Meier curves, with estimates of median time to event (95% CI by log-log transform), and selected time-specific survival rates (95% CI).

Time to first recurrence (TTR) -Post-surgery times to event36 months

Post-surgery times to event (TTR) will be measured in months throughout the duration of the study (36 months). Time to first recurrence (TTR) is the time from surgery to first radiological or pathological evidence of recurrence, excluding second primary cancers. TTR will be summarized by Kaplan-Meier curves, with estimates of median time to event (95% CI by log-log transform), and selected time-specific survival rates (95% CI).

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Trial Sites

This study has 1 trial site

Baylor College of Medicine

Houston, Texas, US

Name:Hector J Garcia-Chavez, MD

Email:hector.garcia-chavez@bcm.edu

Phone:713-798-6419

Recruiting

Houston, Texas, 77030 US

Baylor College of Medicine

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