Phase II Open-label Trial of Neoadjuvant Immunochemotherapy for Resectable Non-metastatic Colon cancER: NICER
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-80
SponsorBaylor College of Medicine
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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)
Trial design
Design model
Single group
Treatments tested in this trial
Tecentriq 1200 MG in 20 ML Injection + Capecitabine 1000 mg/m2 + Oxaliplatin 130 mg/m2
DrugEnrolled Participant will receive 4 cycles of neoadjuvant Atezolizumab (Tecentriq) followed by CAPOX chemotherapy prior to surgery. Each cycle is every 3 weeks. (12 weeks)
Oxaliplatin injection 85mg/m2 + Leucovorin 400mg/m2 + 5-Fluorouracil 2400mg/m2
DrugAfter 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)
Oxaliplatin 130mg/m2 + Capecitabine 1000mg/m2
DrugAfter 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)
Treatment groups
28 Participants
are divided into 1 treatment groupGroup A: Neoadjuvant Therapy ArmExperimental treatment 3 interventions
Trial outcomes
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.
Time frame
3-5 monthsSecondary outcomes
1
Complete pathologic response (TRG-0) to neoadjuvant immunochemotherapy or not.
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.
Time frame
36 months2
R0 resection and number of lymph nodes harvested after neoadjuvant combination CAPOX / Atezolizumab
R0 resection rate will be summarized as described for the primary endpoint.
Time frame
3-4 months3
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.
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.
Time frame
36 months4
Occurrence of any grade 3 or greater adverse events possibly, probably or definitively related to the neoadjuvant CAPOX / Atezolizumab combination
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.
Time frame
3-12 monthsSponsors and contacts
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Baylor College of Medicine
Lead sponsor
Genentech, Inc.
Collaborator
Source ClinicalTrials.gov