Safety and Efficacy of Atezolizumab Combined to Preoperative Radio-chemotherapy in Localized Rectal Cancer

NCT03127007 | Completed Phase 1

• 1 other identifier: ONCOGHdC2015_02
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 5

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.

Conditions

Rectal Neoplasms

Keywords

immunotherapy; anti-PD-L1

Outcome Measures

Primary Outcomes (2)

• Rate of adverse events

  Evaluation of adverse events use CTCAE v4.0 terminology

  74 weeks

• Rate of complete pathological response

  Evaluation by central pathological review of rectal tumor resected after the preoperative treatment

  15 weeks

Study Arms (2)

Arm A

EXPERIMENTAL

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

Drug: Atezolizumab; Drug: 5-FU based radio-chemotherapy

Arm B

ACTIVE COMPARATOR

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

Drug: 5-FU based radio-chemotherapy

Interventions

Atezolizumab DRUG

Atezolizumab is given on day 1 of week 3, 6, 9 and 12 at 1200 mg IV.

Also known as: Tecentriq, MPDL3280a

Arm A

5-FU based radio-chemotherapy DRUG

IV protracted 5-FU given at 225mg/m2 over 24h 5 days/week for 5 weeks associated to radiotherapy.

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of \< 1% per year, during the treatment period and for at least 6 months after the last dose of atezolizumab / radio-chemotherapy
• Patients who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

You may not qualify if:

• 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
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1
• Current or prior use of immunosuppressive medication within 28 days before the first dose of atezolizumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• Treatment with systemic immunostimulatory agents (including but not limited to interferons or IL-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization
• Receipt of live attenuated vaccination within 30 days prior first atezolizumab planned administration (i.e. at week 3 after study entry) or within 5 months of receiving atezolizumab or anticipation that such a live attenuated vaccine will be required during the study. Influenza vaccination (inactivated forms only but not live attenuated forms) should be given during influenza season only (approximately October to March).
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction

Sponsors & Collaborators

• Grand Hôpital de Charleroi: lead
• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: collaborator

Study Sites (5)

GHdC

Charleroi, Hainaut, 6000, Belgium

Location

Katholiek universiteit Leuven

Leuven, Vlaams Brabant, 3000, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Hôpital Erasme

Brussels, 1070, Belgium

Location

Cliniques universitaires St Luc

Brussels, 1320, Belgium

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Javier Carrasco, MD, PhD

  GHdC

  PRINCIPAL INVESTIGATOR

• Marc Van den Eynde, MD, PhD

  Cliniques universitaires Saint-Luc- Université Catholique de Louvain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2017
• First Posted: April 25, 2017
• Study Start: April 27, 2017
• Primary Completion: February 22, 2024
• Study Completion: October 15, 2024
• Last Updated: January 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (5)