This is a Phase II open-label trial of neoadjuvant immunochemotherapy with Atezolizumab + CAPOX chemotherapy followed by surgery and adjuvant chemotherapy (only for high-risk patients) for patients with localized resectable pMMR adenocarcinoma of the colon with a target accrual of 28 patients. The investigational medicinal product (IMP) for this study is atezolizumab. Neoadjuvant CAPOX chemotherapy regimen or category (including rescue medications, premedications), in addition to adjuvant chemotherapy regimens (mFOLFOX6 and CAPOX) are considered non investigational medicinal products (NIMPs).
Please note all RESEARCH ONLY PROCEDURES ARE MARKED WITH A " \* " BASELINE VISIT
Once eligibility of potential subjects is confirmed and consent is obtained eligible subjects will undergo the following procedures:
1. Informed Consent \*
2. History \& Physical exam
3. Vital Signs
4. Assessment of concomitant medications
5. Performance Status (ECOG)
6. PRO/QOL assessments (Research)\*
7. Eligibility Assessment\*
8. Routine Imaging and Laboratory
9. Blood collection for ctDNA analysis (mandatory) and biobanking (optional)\*
10. Stool collection\*
11. Urine pregnancy test
NEOADJUVANT THERAPY (RESEARCH) After baseline assessments and eligibility has been confirmed, patients will receive 4 cycles of neoadjuvant immunochemotherapy for a total of 12 weeks. Therapy consists of Atezolizumab in combination with CAPOX (capecitabine + oxaliplatin) before standard-of-care surgical resection. Each cycle of neoadjuvant therapy is 3 weeks. After completion of neoadjuvant therapy, patients will be evaluated during a presurgical evaluation visit for follow-up of any side effects that could potentially arise from therapy and to determine readiness for surgical removal of the tumor (staging evaluation and assessment of response). During this evaluation visit repeat imaging (CT scan or MRI) will be obtained between 2-8 weeks following completion of neoadjuvant therapy. During each cycle the following assessments will be evaluated\*:
1. History \& Physical exam \*
2. Vital Signs \*
3. Adverse event assessment\*
4. Assessment of concomitant medications \*
5. Administration of neoadjuvant therapy with Aztezoluzumab and CAPOX chemotherapy\*
6. Routine laboratory assessments\*
7. Blood collection for ctDNA analysis (mandatory) and biobanking (optional) during mid-therapy and at conclusion of therapy\*
8. Stool collection (after each cycle)\*
9. Imaging for disease restaging and therapy response (CT or MRI) of abdomen and pelvis will be obtained after neoadjuvant therapy (2-4 weeks after neoadjuvant therapy)
* \*All assessments for this visit are considered research.
SURGERY Surgical removal of the tumor will be performed per standard-of-care practices. Tumor sample will be obtained per standard of care procedure and will be used after final diagnosis by pathology.
POSTOPERATIVE FOLLOW-UP AND ADJUVANT CHEMOTHERAPY Efficacy Follow-up phase (week 2, month 3 \& month 6) Long-term (survival) Follow-up phase (Months 12-36)
Following surgery, patients will enter an efficacy follow-up phase (initial 6 months) and a long-term (survival) follow-up phase (months 12-36). Patients still considered to be at high risk of recurrence (per NCCN guidelines) will receive further adjuvant chemotherapy based on protocol and the discretion of the treating oncologist/investigator.
EFFICACY FOLLOW-UP PHASE ( Week 2 postop and Months 3, 6) Patients will be followed up for an efficacy follow-up phase during first 2 weeks postop and months 3 and 6 and will complete the following assessments:
1. History \& Physical exam
2. Vital Signs
3. Adverse event assessment\*
4. Assessment of concomitant medications
5. Quality of life assessments (satisfaction survey at week 2 and month 3 only)\*
6. Vital status update\*
7. Assessment of adjuvant therapy\*
8. Blood collection for ctDNA analysis and biobanking\* (ctDNA blood draw only at week 2 visit)
9. Stool collection \*
10. Adjuvant chemotherapy with standard of care chemotherapy (ONLY FOR HIGH-RISK PATIENTS)
11. Laboratory analysis (CEA,CBC \& Chemistry panel)(3 \& 6 months only)
12. Standard of care imaging (6 months only)
LONG TERM/ SURVIVAL FOLLOW-UP PHASE Patients will be followed up for an long-term (survival) follow-up phase during months 12, 18, 24, 30, and 36 and will complete the following assessments:
1. History \& Physical exam
2. Vital Signs
3. Adverse event assessment\*
4. Assessment of concomitant medications
5. Quality of life assessments\*
6. Vital status update\*
7. Blood collection for biobanking (these samples are optional) \*
8. Stool collection \*
9. Standard of care imaging
Research procedures:
1. Blood and stool samples will be collected for ctDNA analysis (mandatory) and for banking (optional) at baseline and throughout different stages of the study for future exploratory analysis. The optional blood samples will be stored at Baylor College of Medicine main campus in the ABBR (Alkek Building for Biomedical Research) laboratory and kept for up to 10 years. The purpose of biobanking these samples is for future exploratory research analyses based on future available funding. Stool sample collection kits will be provided to participating subjects which they will be shipping back to our site and collected at several timepoints for storage and future use. In the future stool samples may be used for metabolomic and proteomic profiling. (Costs of shipping back stool kits will be covered by site/sponsor).
2. Quality of life (QOL) outcomes will be obtained through patient- reported outcome (PRO) questionnaires (approx. duration: \~10-20 min per visit) PRO data will be collected through use of the following instruments: MD Anderson Symptom Inventory (MDASI), QLQ C30, and a satisfaction survey. All patients will complete the MDASI, QLQ-C30, and questionnaires at the following timepoints: baseline, after neoadjuvant therapy completion, postoperatively on week 2, months 3, 6, 12, 18, 24, 30, 36. The satisfaction survey will be only collected at week 2 and month 3.
3. Banking procedures: A proper IRB submission will be submitted for request of historic sample controls to previously biobanked specimens within Baylor's biobanks. Historic samples will be deidentified and will be used for comparison. An attempt will be made to match demographics and tumor site but this comparison is going to be used only as an exploratory endpoint.
4. Storage of Data: Each patient will have their own research binder in which research data will be collected. Each subject will be assigned a unique study number ID and will be used throughout the patient's participation. No personal data will be used to identify patients, only the study ID will be used for confidentiality purposes. Data will be captured manually in the patient's binder and electronically in Oncore using study ID number only. Subject binder will be stored in a locked cabinet on the 7th floor at the McNair campus. Only authorized personnel will have access to patient's binder. Information from medical chart that will be used includes: demographic data, concomitant medications, vital signs, medical history, laboratory results, imaging results, notes from office visits, surgery notes, operative notes, progress notes, pathology reports. No information will be shared with any third parties.
