Study With Atezolizumab Plus Bevacizumab in Patients With Chemotherapy Resistant, MSI-like, Colorectal Cancer

NCT02982694 | Terminated Phase 2 DMC

• 2 other identifiers: VHIO16001 - EORTC 16042016-002001-19
• Study Type: interventional
• Target: 46
• Locations: 4 countries
• Sites: 7

Brief Summary

The primary objective of this study is to determine the anti-tumor activity, as measured by overall response rate (ORR) of atezolizumab in combination with bevacizumab in patients with chemotherapy resistant CRC and positivity for MSI-like molecular signature. This is an international, open-label single arm (non-randomized), one-stage phase II trial.

Conditions

MSI; ColoRectal Cancer; Chemotherapy; Resistance, APC

Keywords

MSI; colorectal; chemotherapy; Bevacizumab; Atezolizumab

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  36 months from first patient in

Secondary Outcomes (4)

• Immune-related tumor response

  36 months from first patient in

• Progression Free Survival

  36 months from first patient in

• Overall Survival

  36 months from first patient in

• Safety and tolerability (adverse event assessment according to CTCAE v 4.0)

  36 months from first patient in

Study Arms (1)

Atezolizumab and Bevacizumab

EXPERIMENTAL

Atezolizumab will be administered intravenously at 1200 mg on Day 1 every 3 weeks. The dose of bevacizumab in this study is 7.5 mg/kg administered by IV infusion every 3 weeks on Day 1 of each 21 days cycle. Atezolizumab will be administered first, followed by Bevacizumab, with a minimum of 5 minutes between dosing. The interval between cycle infusions must not be \< 10 days.

Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Atezolizumab DRUG

Atezolizumab will be administered 1200 mg in 250 ml 0.9% NaCl IV infusion bag, on day 1 of each cycle of 21 days.

Also known as: TECENTRIQ

Atezolizumab and Bevacizumab

Bevacizumab DRUG

Bevacizumab will be administered 7.5 ml/kg (diluted in 0.9% sodium chloride solution) on day 1 of each 21 days cycle.

Also known as: Avastin

Atezolizumab and Bevacizumab

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 must be given according to ICH/GCP and national/local regulations.
• Histological or cytological proof of metastatic CRC.
• Disease progression or relapse after at least one line of treatment for advanced CRC with a fluoropyrimidine containing chemotherapy as single agent or in combination (combinations with oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab are allowed).
• Written documentation of positivity for MSI-like gene signature as determined by Agendia test.
• Unresectable disease, with at least one measurable lesion according to RECIST 1.1.
• Age ≥ 18 years.
• WHO performance status of 0-1.
• Ability and capacity to comply with study and follow-up procedures.
• Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 28 calendar days prior to the first study treatment:
• ANC \> 1.5 x 109/L (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
• WBC counts \> 2500/μL
• Platelet count \> 100,000/ μL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
• Hemoglobin \> 9.0 g/dL
• AST, ALT, and alkaline phosphatase \< 2.5 x ULN, with the following exceptions:
• Patients with documented liver metastases: AST and ALT \< 5 x ULN

You may not qualify if:

• Any treatment with investigational drugs (bevacizumab is not considered investigational drug in CRC) within 28 days prior to Cycle 1, Day 1.
• Previous cytotoxic agent within 14 days of planed treatment initiation.
• Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI)
• Note: Patients with treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
• Evaluable or measurable disease outside the CNS
• No metastases to midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
• No history of intracranial or spinal cord haemorrhage
• No ongoing requirement for dexamethasone as therapy for CNS disease; anticonvulsants at a stable dose are allowed.
• No evidence of significant vasogenic edema.
• No stereotactic radiation, whole-brain radiation or neurosurgical resection within 4 weeks prior to Cycle 1, Day 1.
• Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening radiographic study.
• Screening CNS radiographic study \> 4 weeks since completion of radiotherapy or surgical resection and \> 2 weeks since discontinuation of corticosteroids.
• Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated at least 14 days prior to Cycle 1, Day 1.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
• Previous (within the last 5 years) or concurrent malignancies, with the exception of those treated with expected curative outcome as cone-biopsied in situ carcinoma of the cervix, basal cell carcinoma of the skin, localized prostate cancer or ductal carcinoma in situ of the breast.

Sponsors & Collaborators

• Vall d'Hebron Institute of Oncology: lead
• European Organisation for Research and Treatment of Cancer - EORTC: collaborator

Study Sites (7)

KU Leuven

Leuven, Belgium

Location

Ospedale Niguarda CA Granda

Milan, Italy

Location

Second University of Naples

Naples, Italy

Location

The Netherlands Cancer Institute

Amsterdam, Netherlands

Location

Institut Català d'Oncologia

Barcelona, Spain

Location

Vall d'Hebron Institute of Oncology

Barcelona, Spain

Location

Fundación Investigación Clínico de Valencia

Valencia, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Activated Protein C Resistance

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Thrombophilia; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Josep Tabernero Caturla, Prof

  Vall d'Hebron Institute of Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2016
• First Posted: December 5, 2016
• Study Start: November 24, 2017
• Primary Completion: November 27, 2020
• Study Completion: November 27, 2020
• Last Updated: October 1, 2025

Record last verified: 2025-09

Locations

NL (1); ES (3); BE (1); IT (2)