BIBW 2992 as add-on to Gem/Cis in Advanced Biliary Tract Cancer

NCT01679405 | Terminated Phase 1 Results

• 1 other identifier: BIBW 2992
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

An open-label, uncontrolled, multicenter phase I/Ib trial to investigate safety and efficacy of BIBW 2992 added to the standard therapy of Gemcitabine/Cisplatin in chemo-naïve patients with advanced and/or metastatic adenocarcinoma of the biliary tract

Conditions

Metastatic Disease

Keywords

metastatic biliary tract cancer

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events

  In part A the maximum tolerated dose (MTD) of BIBW 2992 administered continuously to the standard therapy of Gemcitabine / Cisplatin (Gem/Cis) (administered together on day 1 and 8 of a three-week cycle) will be evaluated in a 2 step dose escalation. Safety and toxicity will be evaluated as described and considered primary for part B of the study.

  Treatment period: up to eight cycles (maximum 8 months). 12 months follow-up period.

Secondary Outcomes (4)

• Time to Progress (TTP)

  Treatment period: up to eight cycles (maximum 8 months). 12 months follow-up period.

• Overall Survival (OS)

  Time from start of treatment to death due to any cause. Time to last observation will be used if a patient has not died and OS for the patient will be considered censored. Estimated time period: up to 76 weeks

• Objective Response Rate

  Treatment period: up to eight cycles (maximum 8 months).

• Tumor Control Rate

  Treatment period: up to eight cycles (maximum 8 months).

Study Arms (2)

Dose level 1 (Part A)

EXPERIMENTAL

30 mg BIBW 2992, Gemcitabin (1.000 mg/m² BSA i.v.)/Cisplatin (25 mg/m² BSA i.v.)

Drug: BIBW 2992

Dose level -1 (Part A)

EXPERIMENTAL

30 mg BIBW 2992, Gemcitabin (800 mg/m² BSA i.v.)/Cisplatin (20 mg/m² BSA i.v.)

Drug: BIBW 2992

Interventions

BIBW 2992 DRUG

once daily per os

Also known as: Gemcitabine and Cisplatin

Dose level -1 (Part A); Dose level 1 (Part A)

Eligibility Criteria

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

You may qualify if:

• Male and female patients aged ≥ 18 years
• Signed and dated written informed consent,
• Histologically confirmed adenocarcinoma of the gallbladder or intrahepatic bile ducts or extrahepatic bile ducts (metastasized) or histologically proven hepatic metastases of an earlier resected and histologically proven biliary tract cancer or a Klatskin tumour (hilar cholangiocarcinoma)
• with pain and biliary obstruction controlled
• adequate biliary drainage, no uncontrolled infection
• ECOG Performance Status of 0-1
• LFTs: bilirubin (total) ≤ 1.5 x ULN, ALT/ AST/ alkaline phosphatase ≤ 3 2.5 x ULN (≤ 5 x ULN if liver metastases are present)
• No prior systemic treatment i) previous adjuvant chemotherapy is allowed (completed ≥ 6 months if containing Gemcitabine or platinum salts); ii) previous irradiation (external radiotherapy, brachytherapy, chemoembolization) and PDT are allowed, provided that there is still at least one unidimensionally measurable target lesion in an untreated area
• Resolution of all side effects of prior surgical procedures to CTCAE grade ≤ 1 (except for the laboratory values specified below)
• At least 4 weeks from any major surgery (at first dose of study drug)
• Life expectancy of at least 12 weeks.
• Cardiac left ventricular function with resting ejection fraction (LVEF) ≥ 50%
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of therapy:
• Haemoglobin \> 10.0 g/dl (=6.2 mmol/l), blood transfusion is allowed
• Absolute neutrophil count (ANC) \> 1,500/mm3 (=1.5x 109/L)

You may not qualify if:

• Large surgery (except diagnostic biopsy) or smaller surgical procedures, external radiotherapy, brachytherapy, or PDT within 30 days prior to start of treatment.
• Other tumor type than adenocarcinoma (e.g. leiomyosarcoma, lymphoma) or a second cancer except in patients with squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix which has been effectively treated.
• History of acute cardiac disease: congestive heart failure \> NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed);
• Patients on immunosuppressant therapy or with known HIV infection
• Active clinically serious infections (\> grade 2 NCI-CTC version 3.0)
• History of organ allograft
• Pregnant or breast-feeding patients.
• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation
• Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
• Gastrointestinal (GI) tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease
• History of pre-existing interstitial lung disease (ILD)
• Patients with untreated or symptomatic brain metastases.
• Persistent Grade 2 or greater neurotoxicity / neuropathy from any cause

Sponsors & Collaborators

• Johannes Gutenberg University Mainz: lead

Study Sites (1)

I. Medizinische Klinik und Poliklinik der Universitätsmedizin

Mainz, 55131, Germany

Location

Related Publications (1)

• Moehler M, Maderer A, Ehrlich A, Foerster F, Schad A, Nickolay T, Ruckes C, Weinmann A, Sivanathan V, Marquardt JU, Galle PR, Woerns M, Thomaidis T. Safety and efficacy of afatinib as add-on to standard therapy of gemcitabine/cisplatin in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, phase I trial with an extensive biomarker program. BMC Cancer. 2019 Jan 11;19(1):55. doi: 10.1186/s12885-018-5223-7.

  PMID: 30634942 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Biliary Tract Neoplasms

Interventions

Afatinib; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Prof. Dr. Markus Moehler
• Organization: University Medical Center Mainz

Markus.Moehler@unimedizin-mainz.de

0049613117

Study Officials

• Markus Moehler, Prof. Dr. med.

  University Medical Center of the Johannes Gutenberg-University Mainz

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: For Part A of the study a standard 3+3 design was used. The recruitment was carried out in cohorts. Subjects were not allowed to participate in both cohorts. If the maximum tolerated dose was found there should be additional patients recruited to confirm the maximum tolerated dose (part B)

Study Record Dates

• First Submitted: August 17, 2012
• First Posted: September 6, 2012
• Study Start: August 1, 2012
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: September 6, 2019
• Results First Posted: January 22, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)