Combination of Targeted and Immunotherapy for Advanced Biliary Tract and Esophagogastric Gastric Cancer

NCT03818997 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: EORTC 1741-GITCG
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

In this study, non-operable esophagogastric adenocarcinoma cancer patients or non-operable biliary cancer patients whose cancer progressed/spread/got worse after first line treatment will be treated with or without immunotherapy and chemotherapy. This study will take place in several countries across Europe. One hundred twenty-three (123) patients will be invited to participate in this study Biliary tract cancer (BTC), is a form of cancer that start in your bile ducts, a series of tubes that runs from the liver to the small intestines. It is not know yet the exact cause of BTC. For patients who have advanced or metastatic BTC (where surgery is not possible), chemotherapy is the first option for treatment. Chemotherapy with cisplatin and gemcitabine (CisGem) is the current standard of care. Esophagogastric cancer (EGC) is cancer that occurs in the esophagus, a long hollow tube that runs from your throat to your stomach. The accumulating abnormal cells form a tumor in the esophagus that can grow to invade nearby structures and spread to other parts of the body. It's thought that chronic irritation of your esophagus may contribute to the changes that cause esophageal cancer. The purpose of this study is to look at the risks and benefits of combining DKN-01 and atezolizumab (humanized monoclonal antibody) with or without paclitaxel (chemotherapy). Immune therapy boosts the body's natural defenses to fight cancer. It uses specific products made either by participants' body or in a laboratory to improve, target or restore immune system function and control or stop cancer. Atezolizumab is such an "immunotherapy" drug. DKN-01 is another new type of drug (humanized monoclonal antibody) in development as anticancer agent. Paclitaxel is a commonly-used chemotherapy drug of the class of taxanes used to treat a number of cancer types, it stimulates the cell to die or to stop the cell from dividing into two new cells.The idea behind combining these drugs is linked to targeting the immune system to attack the tumor. Combining immune and chemotherapy has already demonstrated clinical activity in relapsed (return of the disease)/refractory (not responding to treatment) esophagogastric cancer patients.

Conditions

Esophageal Cancer; Biliary Tract Cancer; GastroEsophageal Cancer; Hepatobiliary Neoplasm

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Objective response rate according to RECIST v1.1 is computed as the rate of complete and partial responses (with response confirmation)

  6 months from start of study treatment

Secondary Outcomes (7)

• Best overall response distribution

  6 months from start of study treatment

• Immune objective response rate according to iRECIST

  6 months from start of study treatment

• Duration of response using RECIST 1.1 and iRECIST

  Until 2 years after start of study treatment

• Progression free survival according to RECIST 1.1 and iRECIST

  Until 2 years after start of study treatment

• Occurrence of adverse events

  Until 2 years after start of study treatment

Study Arms (3)

BTC Cohort

EXPERIMENTAL

Patient in BTC cohort will receive immune therapy and DKN-01 IV until PD

Drug: DKN-01; Drug: Atezolizumab

EGC cohort: DKN-01/atezolizumab + paclitaxel (Arm 1)

EXPERIMENTAL

Patient randomized in the EGC Arm 1 will receive immune therapy, DKN-01 and chemotherapy intravenously (IV) until PD.

Drug: DKN-01; Drug: Atezolizumab; Drug: Paclitaxel

EGC cohort: DKN-01/atezolizumab without paclitaxel (Arm 2)

EXPERIMENTAL

Patient randomized in the EGC Arm 2 will receive immune therapy and DKN-01 IV until PD

Drug: DKN-01; Drug: Atezolizumab

Interventions

DKN-01 DRUG

Patient will receive DKN-01 300 mg IV every 2 weeks

BTC Cohort; EGC cohort: DKN-01/atezolizumab + paclitaxel (Arm 1); EGC cohort: DKN-01/atezolizumab without paclitaxel (Arm 2)

Atezolizumab DRUG

Patient will receive Atezolizumab 840 mg IV every 2 weeks until PD

Also known as: Tecentriq

BTC Cohort; EGC cohort: DKN-01/atezolizumab + paclitaxel (Arm 1); EGC cohort: DKN-01/atezolizumab without paclitaxel (Arm 2)

Paclitaxel DRUG

Patient will receive Paclitaxel 80 mg/m2 IV on day 1, 8 and 15 of a 28 day cycle until PD

EGC cohort: DKN-01/atezolizumab + paclitaxel (Arm 1)

Eligibility Criteria

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

You may qualify if:

• Histologically proven diagnosis of metastatic or locally unresectable adenocarcinoma of the biliary tract or esophagogastric adenocarcinoma.
• Measurable disease by CT/MRI (RECIST 1.1) within 28 days of randomization/enrollment
• Male and female subjects of age ≥18 years
• Performance status ECOG 0-1
• Life expectancy ≥ 4 months
• Normal 12-lead ECG (patients with abnormal ECG will be eligible if changes are not considered clinically significant by the local investigator)
• Adequate hematological function
• Hemoglobin ≥ 9 g/dl (prior transfusions are allowed if they have been done ≥ 7 days before testing the Hb)
• White blood cell (WBC) ≥ 3.0 x 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 75 x 109/L
• Adequate liver function: screening labs should be performed within 7 days prior to randomization/enrollment:
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN), except subjects with Gilbert Syndrome who must have a total bilirubin level of \< 3.0 x ULN.
• ALT, AST \& alkaline phosphatase ≤ 3 x ULN; ≤ 5 x ULN in case of liver/bone metastases
• Serum albumin ≥ 2.5 g/dL

You may not qualify if:

• Subjects with pleural effusion, pericardial effusion, or ascites with symptoms uncontrolled by medication or who requirere current drainage procedures (once monthly or more frequently).
• Leptomeningeal spread of disease.
• Patient is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks prior to enrollment
• Other concomitant or prior malignancy within the last 5 years, with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix.
• History of inflammatory bowel disease or any autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, type I diabetes mellitus, vasculitis, or glomerulonephritis
• Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study.
• Patients with controlled Type I diabetes mellitus on a stable insulin regimen are eligible.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover less than 10% of body surface area.
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• Occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• History of radiation pneumonitis/fibrosis in the radiation field is permitted.
• Infections:
• Signs or symptoms of infection or therapeutic use of antibiotics (except prophylactic antibiotics) within 2 weeks prior to randomization and severe infections within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Hoffmann-La Roche: collaborator
• Leap Therapeutics, Inc.: collaborator

MeSH Terms

Conditions

Esophageal Neoplasms; Biliary Tract Neoplasms

Interventions

atezolizumab; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Biliary Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Markus Moehler

  Universitaetsmedizin - Mainz University Medical Center, Mainz, Germany

  STUDY CHAIR

• Maria Alsina

  Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: January 24, 2019
• First Posted: January 28, 2019
• Study Start: December 1, 2019
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2022
• Last Updated: February 5, 2020

Record last verified: 2020-02