A Phase Ib/II Study to Evaluate Safety and Efficacy of Atezolizumab Combined With Radio-chemotherapy in a Preoperative Setting for Patients With Localized Rectal Cancer
Overview
- Phase
- Phase 1
- Intervention
- Atezolizumab
- Conditions
- Rectal Neoplasms
- Sponsor
- Grand Hôpital de Charleroi
- Enrollment
- 45
- Locations
- 5
- Primary Endpoint
- Rate of adverse events
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The study has a phase Ib and a phase II part. The phase Ib part of the study aims to determine the safety and tolerance of administration at a fixed dosing of 1200 mg / 3 weeks, concomitantly to the standard preoperative radio-chemotherapy.
The phase II part of the study aims to explore efficacy of atezolizumab in combination with the standard preoperative chemo/radiotherapy in stage II and III rectal cancers.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent and any locally-required authorization are obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
- •Male or female \> 18 years at time of study entry
- •Patients with previously untreated localized T3-T4 N0 or T any or N1-2, M0 rectal adenocarcinoma requiring preoperative radiotherapy
- •Availability of protocol required screening tumor and blood samples
- •ECOG performance status of 0 or 1
- •Adequate normal organ and marrow function:
- •haemoglobin ≥ 9.0 g/dL, absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3), platelet count ≥ 100 x 109/L (\>100,000 per mm3).
- •Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
- •AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit
- •Serum creatinine CL \> 30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance
Exclusion Criteria
- •Patient has locally recurrent or metastatic RC
- •Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current rectal cancer disease
- •Patients not requiring preoperative radio-chemotherapy
- •Participation in another clinical study with an investigational product for any other indication until 4 weeks before study participation
- •Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 21 days prior to the first dose of study drug
- •Any previous treatment with a PD1 or PD-L1 inhibitor, including atezolizumab
- •History of another primary malignancy except for:
- •Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- •Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ
Arms & Interventions
Arm A
Protracted IV 5-FU 225 mg/m2 is given from day 1 to 5 in parallel with radiotherapy 1.8 to 2 Gy from day 1 to 5 during 5 consecutive weeks. Atezolizumab is given on day 1 of week 3, 6, 9 and 12 at 1200 mg IV. Rectal surgery is planned during week 15
Intervention: Atezolizumab
Arm A
Protracted IV 5-FU 225 mg/m2 is given from day 1 to 5 in parallel with radiotherapy 1.8 to 2 Gy from day 1 to 5 during 5 consecutive weeks. Atezolizumab is given on day 1 of week 3, 6, 9 and 12 at 1200 mg IV. Rectal surgery is planned during week 15
Intervention: 5-FU based radio-chemotherapy
Arm B
Protracted IV 5-FU 225 mg/m2 is given from day 1 to 5 in parallel with radiotherapy 1.8 to 2 Gy from day 1 to 5 during 5 consecutive weeks. Rectal surgery is planned during week 15
Intervention: 5-FU based radio-chemotherapy
Outcomes
Primary Outcomes
Rate of adverse events
Time Frame: 74 weeks
Evaluation of adverse events use CTCAE v4.0 terminology
Rate of complete pathological response
Time Frame: 15 weeks
Evaluation by central pathological review of rectal tumor resected after the preoperative treatment