Pembrolizumab in Biliary Tract Cancer

NCT03260712 | Completed Phase 2 DMC

• 1 other identifier: EORTC-1607-GITCG / ABC-09
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 7

Brief Summary

This is a single-arm, multi-centre, phase II study in biliary tract cancer (BTC) patients. The main objective is to detect an increase in progression-free survival rate at 6 months (according to RECIST version 1.1) from 60% in patients with BTC treated with standard chemotherapy (CT) approach to 75% when treated with CT combined with pembrolizumab.

Conditions

Biliary Tract Cancer; Metastatic Cancer; Advanced Cancer; Gallbladder Cancer

Keywords

biliary tract cancer; metastitic cancer; advanced cancer; pembrolizumab; cisplatin; gemcitabine; gallbladder cancer

Outcome Measures

Primary Outcomes (1)

• Detection of progression-free survival (PFS) rate at 6 months defined according to RECIST 1.1.

  The main objective is to detect an increase in progression-free survival (PFS) rate at 6 months (according to RECIST version 1.1) from 60% in patients with BTC treated with standard chemotherapy approach to 75% when treated with CT combined with pembrolizumab.

  At 6 months

Secondary Outcomes (3)

• Best overall response rate (according to RECIST 1.1) and overall response

  Up to 120 days after last administration of Pembrolizumab

• Toxicity (according to CTCAE 4.03)

  Up to 120 days after last administration of Pembrolizumab

• Progression free survival rate at 6 months according to iRECIST

  At 6 months

Other Outcomes (4)

• Immunological response (cytokines, lymphocyte phenotype, immunoglobulins)

  Up to 2 years after start of study treatment

• Pathological predictive factors for response and toxicity (TCR Sequencing, FACs, RNASeq, nanostring)

  Up to 2 years after start of study treatment

• Clinical predictive factors for response and toxicity (TCR Sequencing, FACs, RNASeq, nanostring)

  Up to 2 years after start of study treatment

Study Arms (1)

CisGem + pembrolizumab

EXPERIMENTAL

Patients will be enrolled in the experimental arm and will receive CisGem \[25mg/m2 cisplatin + 1000mg/m2 gemcitabine, on days 1 and 8 of a 21 day cycle\] plus 200 mg pembrolizumab (fixed dose) on day 1 of a 21 day cycle.

Drug: Pembrolizumab; Drug: Cisplatin; Drug: Gemcitabine

Interventions

Pembrolizumab DRUG

The dose of pembrolizumab in this trial is 200 mg Q3W.

Also known as: Anti-PD-1

CisGem + pembrolizumab

Cisplatin DRUG

25mg/m2 cisplatin on days 1 and 8 of a 21 day cycle

CisGem + pembrolizumab

Gemcitabine DRUG

1000mg/m2 gemcitabine on days 1 and 8 of a 21 day cycle

CisGem + pembrolizumab

Eligibility Criteria

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

You may qualify if:

• A histopathological / cytological diagnosis of non-resectable or recurrent / metastatic biliary tract carcinoma (intra- or extra-hepatic) or gallbladder
• Availability of archival FFPE tumor tissue for biobanking
• Measurable disease by CT/MRI (RECIST 1.1) within 28 days of enrollment
• ECOG performance status 0, 1
• Age ≥ 18 with estimated life expectancy \>3 months
• Adequate hematological function: screening labs should be performed within 14 days (± 3 days) prior to enrollment:
• Hemoglobin ≥ 10 g/dl\* (prior transfusions for patients with low hemoglobin are allowed)
• White blood cell (WBC) ≥ 3.0 x 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Adequate liver function: screening labs should be performed within 14 days (± 3 days) prior to enrollment:
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• ALT and/or AST \& alkaline phosphatase ≤ 5 x ULN
• Adequate renal function: screening labs should be performed within 14 days (± 3 days) prior to enrollment:
• Serum creatinine \< 1.5 x ULN

You may not qualify if:

• Patients with ascites grade 2 or higher
• Child Pugh B or C hepatic impairment
• Incomplete recovery from previous surgery or unresolved biliary tract obstruction
• Active infection requiring therapy. Antibiotic treatment should have been completed 5 days before enrollment
• Patients who are candidates for curative surgery
• History of (non-infectious) pneumonitis that required steroids or current pneumonitis. No history of or current interstitial lung disease
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Diagnosis of immunodeficiency, systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
• Known history of human immunodeficiency virus (HIV), active Hepatitis B or Hepatitis C
• Patients with hyperthyroidism or hypothyroidism unless stable on hormone replacement
• History of another malignancy or a concurrent malignancy. Exceptions include patients who have been disease-free for 5 years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ.
• Patients who received treatment with live vaccines within 30 days prior to the first dose of study medication. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, seasonal flu, H1N1 flu, rabies, BCG and typhoid vaccine.
• Prior treatment with any anti-CTLA4 monoclonal antibody or anti-PD-1, or PD-L1 or PD-L2 agent. Examples of PD-1 inhibitors (include, but are not limited to): pembrolizumab (Merck); Nivolumab (also known as BMS-936558, MDX-1106, ONO-4538) (Bristol-Myers Squibb); Pidilizumab (CT-11) (Cure-Tech/Teva); and AMP-224 (Amplimmune). Examples of PD-L1 inhibitors (include, but are not limited to): BMS-936559 (also known as MDX-1105) (Bristol-Myers Squibb); MPDL3280A (also known as RG7446) (Roche Genentech); and MEDI4736 (MedImmune).
• Prior systemic chemotherapy for locally advanced or metastatic disease.
• Prior adjuvant chemotherapy is allowed if the last treatment was completed at least 6 months before trial entry and neither gemcitabine nor cisplatin were given. Also the following treatment modalities are allowed within the rules described (provided there has been a full recovery):

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (7)

Universitaetsklinikum Leipzig UCCL-Krebszentrum

Leipzig, 04103, Germany

Location

Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz-University Medical Center

Mainz, 55131, Germany

Location

Vall d'Hebron Institut Oncologia

Barcelona, Spain

Location

Hospital Universitario 12 De Octubre

Madrid, Spain

Location

University College London Hospitals NHS Foundation Trust - University College Hospital

London, NW1 2PG, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Nottingham University Hospitals NHS Trust - City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms; Neoplasm Metastasis; Gallbladder Neoplasms

Interventions

pembrolizumab; spartalizumab; Cisplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Markus Moehler, Prof. Dr.

  Johannes Gutenberg Universitaetskliniken - Mainz University Medical Center

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: August 8, 2017
• First Posted: August 24, 2017
• Study Start: January 7, 2020
• Primary Completion: April 27, 2023
• Study Completion: August 31, 2023
• Last Updated: November 3, 2023

Record last verified: 2023-11

Locations

DE (2); ES (2); GB (3)