Phase Ib/II Single-arm Study of mFOLFOX6, Bevacizumab and Atezolizumab in Advanced Biliary Tract Cancer

NCT05052099 | Completed Phase 1 DMC

• 1 other identifier: MO40094
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 2

Brief Summary

The main objective of the study is to establish if patients with advanced bile duct cancer, who have already received a line of treatment for their disease, will receive any associated benefits from the combination of mFOLFOX6, bevacizumab and atezolizumab as a second-line therapy All patients who meet the criteria to participate in the study shall receive the following drugs intravenously every 14 days: mFOLFOX6 combined with Atezolizumab 840 mg and Bevacizumab 10 mg/kg. These drugs will be administered until one of the following situations arises: disease progress, intolerable side effects, pregnancy or if the patient or the doctor decide to stop the treatment. Atezolizumab is an antibody that operates on an important receptor of the immune system (PD1/PD-L1 axis). Atezolizumab (Tecentriq®) has already been approved in a number of countries to treat a range of tumours, although it has not yet been approved for bile duct tumours. Bevacizumab is an antibody that is joined to the vascular endothelial growth factor (VEGF). Bevacizumab was approved for the first time in the USA in 2004 and is now approved in over 100 countries around the world for a variety of conditions. However, it has not yet been approved for treating bile duct cancers. mFOLFOX6 is a chemotherapy regime used to treat many kinds of gastrointestinal tumours, including bile duct cancer, since it is a treatment approved for this type of tumour. The combination of mFOLFOX6 with atezolizumab and bevacizumab (trial drugs), may bring more information about an anti-tumour immune response that could improve the results of mFOLFOX6, which backs up the research on this treatment combination with cancer patients.

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Proportion of patients with a complete response (CR) or partial response (PR), determined by the investigator (INV) following RECIST v1.1.

  12 weeks

Secondary Outcomes (9)

• Disease control rate (DCR)

  12 and 18 weeks

• Duration of objective response (DOR)

  12 weeks

• Best Objective Response Rate (BORR),

  through study completion, an average of 9 months

• Progression-free survival (PFS)

  through study completion, an average of 9 months

• Time to treatment failure (TTF)

  through study completion, an average of 9 months

Study Arms (1)

mFOLFOX6 combined with Atezolizumab and Bevacizumab

EXPERIMENTAL

Patients will receive mFOLFOX6 combined with Atezolizumab 840 mg and Bevacizumab 10 mg/kg in 14-day cycles. Treatment will be continued until disease progression, unacceptable toxicity or voluntary withdrawal.

Drug: mFOLFOX6, Atezolizumab and Bevacizumab

Interventions

mFOLFOX6, Atezolizumab and Bevacizumab DRUG

All study medication is administered by intravenous (IV) infusion on Day 1 of each 14-day cycle: • mFOLFOX6 consisting of Folinic acid (Leucovorin) 400 mg/m2 (D,L racemic form) or 200 mg/m2 (L-isomer form \[levo leucovorin\]), 5-fluorouracil (5-FU) 2400 mg/m2 and Oxaliplatin 85 mg/m2 combined with * Atezolizumab 840 mg and * Bevacizumab 10 mg/kg

mFOLFOX6 combined with 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:

• Signed informed consent form
• Ability to comply with the study protocol, in the investigator's judgment
• Histologically confirmed advanced BTC
• Patient must have received at least one prior line of systemic therapy in advanced-stage BTC
• Adjuvant or neoadjuvant chemotherapy is allowed, provided it is completed at least 6 months before start of study treatment
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
• Life expectancy \> 12 weeks
• Measurable disease, according to RECIST v1.1. Lesions intended to be biopsied should not be defined as target lesions
• Tumor must be accessible for biopsies and patient willing to provide tissue from a newly obtained biopsy of a tumor lesion. In exceptional cases, if a pre-treatment biopsy is not deemed feasible by the investigator, archival biopsies can be used after Sponsor approval has been obtained, as long as they were collected no more than 6 months prior to enrollment.
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment.
• For women of childbearing potential: Negative serum pregnancy test within 21 days prior to Cycle 1 Day 1 (C1D1). Agreement to remain abstinent (refrain from heterosexual intercourse) or use of contraceptive methods that result in a failure rate of ≤ 1% per year during the treatment period and for at least 180 days after the last study treatment
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm.

You may not qualify if:

• Malignancies other than BTC within 3 years prior to C1D1 with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year overall survival \> 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically, ductal carcinoma in situ treated surgically)
• Patients with known microsatellite instability high (MSI-H) status. Patients with unknown MSI status are eligible and the MSI status will be analyzed retrospectively. Patients who are then determined to be MSI-H will be allowed to continue the study treatment, but will be replaced by microsatellite-stable (MSS) or MSI-low tumors.
• Untreated central nervous system (CNS) metastases. Treatment of brain metastases, either by surgical or radiation techniques must have been completed at least 4 weeks prior to initiation of study treatment.
• Radiation therapy within 21 days prior to C1D1 and/or persistence of radiation-related adverse effects
• Prior allogeneic bone marrow transplantation or solid organ transplant for another malignancy in the past
• Spinal cord compression not definitively treated with surgery and/or radiation
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Uncontrolled tumor pain. Patients who require narcotic pain medication during screening should be on a stable dose regimen prior to C1D1. Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
• Treatment with any investigational agent or approved therapy within 14 days or two investigational agent half-lives (whichever is longer) prior to C1D1
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-PD-1 and anti-PD-L1, or VEGF/VEGFR inhibitors
• Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene polymorphism predisposing the patient for 5-fluorouracil (5-FU) toxicity
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any components of atezolizumab or bevacizumab formulations
• Current or recent (within 10 days of study enrollment) use of acetylsalicylic acid (\> 325 mg/day), clopidogrel (\> 75 mg/day) or thrombolytic agents for therapeutic purposes
• History of clinically significant cardiac or pulmonary dysfunction including the following:

Sponsors & Collaborators

• University Hospital, Essen: lead

Study Sites (2)

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

Clínica Universidad de Navarra

Pamplona, 31008, Spain

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jens Siveke, Prof. Dr.

  Universitätsklinikum Essen

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 27, 2021
• First Posted: September 22, 2021
• Study Start: October 22, 2021
• Primary Completion: September 18, 2024
• Study Completion: September 18, 2024
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); DE (1)