Patients with MSI-high or MMR-deficient stage III colorectal cancer who are ineligible for or who refuse oxaliplatin-based chemotherapy after R0 tumor resection (main study) or planned resection (sub-study) MedDRA version: 21.0 Level: PT Classification code 10009955 Term: Colon cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10009966 Term: Colon carcinoma stage III System Org
Conditions
Interventions
Trade Name: Tecentriq (R)
Product Name: Atezolizumab
Product Code: L01XC32
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
CAS Number: 1380723-44-3
Concent
Sponsors
AIO-Studien-gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent including participation in translational research and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations 2. Male or female = 18 years of age 3. Histologically confirmed adenocarcinoma of the colon or rectum 4. For the main study: Pathological stage II high risk or Stage III disease. For the perioperative sub-study: Clinical staged T3-4 and/or nodal positive colorectal cancer without distant metastases 5. For the main study: R0 or R1-resected primary tumor For the perioperative sub-study: Resectable primary tumor; R0 resection anticipated (R1-resected patients can remain on study.) 6. Tumor is MSI-high (MSI-H) or MMR-deficient (dMMR) For the main study: assessed from biopsy or from resected tumor tissue For the perioperative sub-study: assessed from biopsy 7. ECOG status 0 – 2 8. Ineligible for oxaliplatin-based adjuvant chemotherapy or patient’s refusal of oxaliplatin-based adjuvant chemotherapy 9. Adequate blood count, liver enzymes, and renal function – re-testing can be undergone once in case of initial results near cutoff - White blood cell count = 3.5 x 10^6/mL (Inclusion is also possible if White blood cell = 2,5 x 10^6/mL, in which case the neutrophils must be = 1.5 x 10^9/ml and the lymphocytes = 0.5 x 10^9/ml) - Platelet count = 100 x 10^9/L (>100,000 per mm3) - Hemoglobin = 9 g/dL (blood transfusion > 2 weeks before testing is permitted) - AST (SGOT)/ALT (SGPT) = 5 x institutional upper limit of normal - Serum Creatinine = 1.5 x institutional ULN or a calculated glomerular filtration rate = 30 mL per minute 10. Patients not receiving therapeutic anticoagulation must have an INR =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Severe infection within 4 weeks prior to registration e.g. hospitalization for complications of infection, bacteremia, known active pulmonary disease with hypoxia, or severe pneumonia or any active infection requiring systemic therapy within 4 weeks prior to registration. Patients with positive test result for SARS-CoV2 should be managed as per local institutional guidelines 2.For the main study: Distant metastases or residual disease/For the perioperative sub-study: Distant metastases or macroscopic residual disease (R2 resection status) 3. Neoadjuvant radiotherapy or radio-chemotherapy (rectal cancer patients without prior radio- or radio-chemotherapy allowed); prior neoadjuvant radio-chemotherapy or radiotherapy for rectal cancer is allowed if >5 years and secondary colorectal cancer 4. Prior adjuvant chemotherapy for colorectal cancer; allowed if >5 years and secondary colorectal cancer 5. Prior treatment with atezolizumab or any other checkpoint inhibitor 6. Treatment with systemic immunosuppressive medication within 2 weeks prior to treatment start, or anticipation of need for systemic immunosuppressive medication during study treatment 7. Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrollment. 8. History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins. 9. Known hypersensitivity to CHO cell products or any component of the atezolizumab formulation. 10. 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 CT scan. If any of these lung diseases is suspected based on the patient’s history or the integrated evaluation of clinical and radiological records, an additional spirometry should be conducted. 11. Active HBV infection (chronic or acute), defined as having a positive HBsAg test at screening. Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total HBcAb test at screening followed by a negative HBV DNA test, are eligible for the study. The HBV DNA test will be performed only for patients who have a positive total HBcAb test. Patients are also eligible if HBV DNA < 500 IU/mL obtained within 28 days prior to initiation of study treatment, AND anti-HBV treatment for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study 12. Anti-viral therapy against HCV during the trial (allowed prior to trial) 13. Positive HIV test. As an exception, known HIV+ patients may be included if they have: A stable regimen of HAART; No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections; A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests 14. a) Treatment with a live, attenuated vaccine within 4 weeks prior to first dose of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the last dose of study treatment. b) Treatment with any vaccine during screening and the first cycle of treatment. 15. Active tuberculosis 16. Active or history of autoimmune disease or immune deficiency e.g. myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: main study: To determine whether atezolizumab alone can significantly improve disease-free survival rate at 3 years compared to historical control when used as adjuvant treatment in patients with MSI-high/dMMR stage II high risk or stage III colorectal cancer for whom oxaliplatin regimens are not a viable treatment option sub-study: To assess the efficacy of perioperative atezolizumab (with IMM 101 (Arm B stopped with N=10 with IMM-101, sub-study N=8 with IMM-101)) in patients with MSI-high/dMMR clinical staged T3-4 and/or nodal positive colorectal cancer without distant metastases for whom oxaliplatin regimens are not a viable treatment option in terms of pathological complete (pCR) or subtotal (<10% vital tumor cells) regression after 5 weeks of neoadjuvant treatment;Secondary Objective: main study: determine whether atezolizumab (ATEZO) monotherapy (or ATEZO combined with IMM 101 show promising efficacy (DFS and OS) compared to historical control when used as adjuvant treatment in pats. with MSI-Hhigh/dMMR stage II high risk or stage III colon or rectal cancer for whom oxaliplatin regimens are not a viable treatment option. assess safety and tolerability profile of ATEZO (with/without IMM 101) in pats. with MSI-high stage II high risk or stage III colorectal cancer for whom oxaliplatin regimens are not a viable treatment option determine impact of ATEZO (with/without IMM 101) on PRO and health-related QoL, and functional domains of health-related QoL. sub-study: assess efficacy in terms of DFS and OS. assess safety, tolerability, and QoL of periop. ATEZO monotherapy (with IMM 101) in pats. with MSI-high/dMMR clinical staged T3-4 and/or nodal positive colorectal cancer without distant metastases for whom oxaliplatin regimens are not a viable treatment option ;Primary end point(s): For the main study: The primary efficacy endpoint is disease-free survival (DFS) rate at 3 years, defined as the proportion of patients without relapse or tumor-relate | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For the main study: ? DFS including 1-, and 2-year tumor-specific DFS rates ? Overall Survival (OS) including 1-, 2- and 3-year OS rates Exploratory endpoints ? Rate of patients without detectable ctDNA after 12 months. ctDNA-free is defined as a ctDNA level below the lowest limit of detection of the respective Liquid Biopsy Assay ? Quality of life, assessed by EORTC QLQ-C30 and PRO-CTCAE questionnaires Safety endpoints Safety endpoints in both the main study and the sub-study are the incidence, severity and causality/ relationship of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI). Severity will be assessed using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 5.0 (CTCAE v5.0). In addition, all efficacy, safety and exploratory endpoints of the main study will also be assessed for the sub-study. ;Timepoint(s) of evaluation of this end point: All other efficacy and safety parameters will be evaluated in an explorative or descriptive manner, providing proportions, means, medians, ranges, standard deviations and/or confidence intervals, or Kaplan-Meier estimates, as appropriate. | — |
Countries
Germany
Contacts
Public ContactAIO-Studien-gGmbH
AIO-Studien-gGmbH
Outcome results
None listed