Durvalumab + Tremelimumab ± Paclitaxel in Advanced BTC After Platinum Chemotherapy.

NCT03704480 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: IMMUNO-BIL D18-1 PRODIGE 57
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 28

Brief Summary

IMMUNO-BIL is a non-comparative randomized 1:1 phase II study. This study will assess the efficacy and safety of the combination of durvalumab plus tremelimumab with or without weekly paclitaxel in patients with advanced BTC after failure of platinum-based chemotherapy. On the 25th June 2019, the maximum DLT event number was reached (6/10) in the durvalumab plus tremelimumab combination with paclitaxel Arm (Arm B). According to the Pocock boundary described in the protocol, GERCOR has updated the study to discontinue enrollment in Arm B (durvalumab plus tremelimumab with paclitaxel) . No safety concerns were raised by the IDMC in Arm A. Consequently, the study will resume with Arm A (durvalumab plus tremelimumab) only, without randomization. Discontinuation of ARM B(June 2019): Durvalumab plus tremelimumab plus paclitaxel One cycle equals 4 weeks (D1=D28); Durvalumab: 1,500 mg by IV infusion on D1, until progression or unacceptable toxicity or withdrawal of consent. Tremelimumab: 75 mg by IV infusion on D1 for the first 4 cycles. Paclitaxel: 80 mg/m2, every week for 3 weeks (D1-D8-D15), by IV infusion, until progression or unacceptable toxicity or withdrawal of consent (at least 6 cycles, at the discretion of the investigator). December 2020: Tremelimumab dosage modification based on the results of the Study 22 study (Kelley RK, et al. ASCO20 Virtual Scientific Program 2020) showing increased efficacy (response rate and progression-free survival) without safety concerns with one dose of tremelimumab 300 mg (cycle 1) instead of four doses of 75 mg (cycle 1 to cycle 4) in combination with durvalumab 1,500 mg Q4W in hepatocellular carcinoma. Following these results, we have changed the tremelimumab 75 mg x 4 schedule for the 300 mg x 1 schedule. The inclusion of 106 additional patients will be required to adequately evaluate the efficacy of this administration schedule. ARM A : Durvalumab plus tremelimumab ( patients included before 31/12/2020) One cycle equals 4 weeks (D1=D28); Durvalumab: 1,500 mg by IV infusion on D1, until progression or unacceptable toxicity or withdrawal of consent. Tremelimumab: 75 mg by IV infusion on D1 for the first 4 cycles.

Conditions

Advanced Biliary Tract Carcinoma

Keywords

Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) in amended Arm A

  OS - defined as the time from date of randomization to date of death. In the absence of confirmation of death, survival time will be censored at the date of the last clinical assessment

  At 6 months

Secondary Outcomes (8)

• Safety profile - All grade and severe (grade 3-5)

  From signature of informed consent to 3 months after last study treatment administration

• RECIST v1.1 and iRECIST criteria in arm A and amended Arm A

  At 2 months, evaluation every 2 months during treatment period and end of treatment (until the date of first documented progression or date of death, assessed up to 30 months

• Health-related Quality of life (HRQoL) assessed by EORTC QLQ-C30 questionnaire in Arm A and amended Arm A

  Baseline, every 2 months during treatment period and end of treatment (until the date of first documented progression or date of death)

• Health-related Quality of life (HRQoL) assessed by EORTC QLQ-BIL21 questionnaire

  Baseline, every 2 months during treatment period and end of treatment (until the date of first documented progression or date of death)

• Quality-Adjusted Time Without Symptoms of Disease or Toxicity of Treatment (Q-Twist) in arm A and amended Arm A

  assessed up to 30 months

Study Arms (1)

Amended ARM A

EXPERIMENTAL

One cycle equals 4 weeks (D1=D28); Durvalumab: 1,500 mg by IV infusion on D1, until progression or unacceptable toxicity or withdrawal of consent. Tremelimumab: 300 mg by IV infusion on D1 at cycle 1 only.

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab DRUG

1500mg by intravenous (IV) infusion on D1 until progression or unacceptable toxicity or withdrawal of consent

Also known as: MEDI4736

Amended ARM A

Tremelimumab DRUG

300mg by IV infusion on D1 at cycle 1 only

Also known as: CP-675

Amended ARM A

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 obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
• 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.
• Histologically or cytologically proven BTC (extrahepatic CCA, intrahepatic CCA, or gallbladder carcinoma).
• Failure (documented progression or toxicity) of previous platinum-based (cisplatin or oxaliplatin) therapy (e.g. GEMCIS, GEMOX, FOLFIRINOX) Note: a maximum of 1 previous chemotherapy line is allowed; maintenance therapy with chemotherapy or targeted agent, except immunotherapy, will be permitted.
• Age ≥ 18 years at the time of study entry.
• ECOG PS 0-1.
• Recurrent or advanced disease not amenable to surgery, radiation, or combined modality therapy with curative intent (previous resection of primary tumor allowed).
• Measurable or evaluable (radiologically detectable disease which does not fulfill RECIST criteria for measurable disease) lesions according to RECIST v1.1 criteria (CT-scan \< 3 weeks).
• Have tissue from an archival tissue sample that has been identified and confirmed as available for study, or newly obtained core or excisional biopsy of a tumor lesion.
• Adequate organ function, as defined by the following:
• Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) \< 3 x upper limit of normal (ULN)
• Total serum bilirubin \< 1.5 ULN
• Prothrombin ratio \> 70%
• Serum albumin ≥ 28 g/L
• Hemoglobin ≥ 9.0 g/dl

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) or supportive care clinical study or during the follow-up period of an interventional study.
• Receipt of the last dose of anticancer therapy (investigational product, chemotherapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤ 21 days prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or pharmacokinetics properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca/MedImmune and the investigator.
• Mixed histology (hepatocholangiocarcinoma).
• Extensive tumor massively replacing both entire lobes.
• Obstructive jaundice (bilirubin \> 1.5 ULN) without adequate biliary drainage.
• Patients with Grade ≥ 2 neuropathy will be excluded
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
• History of allogenic organ transplantation.
• Any systemic steroid therapy (\> 10 mg daily dose of prednisone or equivalent) whatever the duration of this corticotherapy
• Note: The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies) Note: Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive hepatitis B core antigen \[HBc\] antibody test) are eligible.

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead
• AstraZeneca: collaborator

Study Sites (28)

CHRU Jean Minjoz

Besançon, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, France

Location

Hôpital Duchenne

Boulogne-sur-Mer, France

Location

CHU Morvan

Brest, France

Location

Hôpital Beaujon

Clichy, France

Location

CHPSO Site de Creil

Creil, France

Location

CHU Henri Mondor

Créteil, France

Location

Centre Georges François Leclerc

Dijon, France

Location

CHU Dijon

Dijon, France

Location

Institut Andrée Dutreix

Dunkirk, France

Location

Institut Hospitalier franco-Britannique

Levallois-Perret, France

Location

CHRU Lille

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Hôpital Privé Jean Mermoz

Lyon, France

Location

Hôpital la Timone

Marseille, France

Location

Hôpital Saint Eloi

Montpellier, France

Location

Hôpital Prive du confluent SAS

Nantes, France

Location

Hôpital Cochin

Paris, France

Location

Hôpital Saint Antoine

Paris, France

Location

Institut Mutualiste Montsouris

Paris, France

Location

Hôpital Haut Lévêque

Pessac, France

Location

CHU Poitiers

Poitiers, France

Location

CHU Robert Debré

Reims, France

Location

Centre Eugène Marquis

Rennes, France

Location

Institut Curie

Saint-Cloud, France

Location

CHI Poissy Saint Germain

Saint-Germain-en-Laye, France

Location

Centre Paul Strauss

Strasbourg, France

Location

Insitut Gustave Roussy

Villejuif, France

Location

Related Publications (1)

• Boileve A, Hilmi M, Gougis P, Cohen R, Rousseau B, Blanc JF, Ben Abdelghani M, Castanie H, Dahan L, Tougeron D, Metges JP, Tournigand C, Garcia-Larnicol ML, Vernerey D, Turpin A, Neuzillet C. Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial. Eur J Cancer. 2021 Jan;143:55-63. doi: 10.1016/j.ejca.2020.10.027. Epub 2020 Dec 3.

  PMID: 33279854 DERIVED

MeSH Terms

Interventions

durvalumab; tremelimumab

Study Officials

• Cindy NEUZILLET

  Institut Curie site de Saint Cloud

  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: September 28, 2018
• First Posted: October 12, 2018
• Study Start: November 9, 2018
• Primary Completion: July 28, 2022
• Study Completion: December 31, 2025
• Last Updated: July 23, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (28)