Metastatic DiseasePhase 1NCT01679405
BIBW 2992 as add-on to Gem/Cis in Advanced Biliary Tract Cancer
A Phase 1 study testing BIBW 2992 in people with Metastatic Disease, run by Johannes Gutenberg University Mainz at 1 site in Germany.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Disease
- What is being tested?
- BIBW 2992
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2012to Apr 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 33Show fewer
- 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)
- Platelet count ≥ 100,000/μl (=100x 109/L)
- Total bilirubin ≤ 1.5 times the upper limit of normal
- ALT and AST ≤ 2.5 x institutional upper limit of normal (in case of liver metastases: ALT and AST ≤ 5 x institutional upper limit of normal)
- Prothrombin rate > 60% or INR < 1.5
- Main exclusion criteria
- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Germany1 site
I. Medizinische Klinik und Poliklinik der Universitätsmedizin
Mainz, 55131
About this study
Official title: Open-label, Uncontrolled, Multicenter Phase I/Ib Trial to Investigate Safety and Efficacy of BIBW 2992 and Standard Gemcitabine/Cisplatin in Chemo-naïve Patients With Advanced Biliary Tract Adenocarcinoma
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
Read the detailed description
The primary objective is safety and toxicity, including maximum tolerated dose, of BIBW 2992 when given as add-on therapy to Gem/Cis.
- Conditions
- Metastatic Disease
- Being tested
- BIBW 2992
- Keywords
- metastatic biliary tract cancer
- Medical subject headings
- Neoplasm Metastasis, Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIBW 2992Drug
Also called Gemcitabine and Cisplatin
once daily per os
| Study group | Role | What they receive |
|---|---|---|
| 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.) Receives: 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.) Receives: Drug: BIBW 2992 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Treatment period: up to eight cycles (maximum 8 months). 12 months follow-up period.
Secondary outcomes (4)
Time to Progress (TTP)
Median time to progress (according to RECIST 1.1 criteria) including the 95% confidence intervals were determined using Kaplan-Meier estimates. Time from start of treatment to first documentation of objective tumour progression. Deaths were censored at the time of death.
Measured: Treatment period: up to eight cycles (maximum 8 months). 12 months follow-up period.
Overall Survival (OS)
Median overall survival time including the 95% confidence interval were determined using Kaplan-Meier estimates.
Measured: 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
Response was assessed by means of RECIST 1.1 criteria for target lesions, non-target lesions and the appearance of new lesions. Objective response was defined as the CR, PR or SD at end of treatment
Measured: Treatment period: up to eight cycles (maximum 8 months).
Tumor Control Rate
Tumor control rate is defined as the best tumour response (confirmed partial or complete response, stable disease) that is achieved until end of treatment according to Recist 1.1.
Measured: Treatment period: up to eight cycles (maximum 8 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2012 (estimated)
- Study startAug 2012
- Primary completionApr 2016
- Study completionApr 2016
Why it stopped: No sufficient clinical or molecular signals for efficacy were observed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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)
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johannes Gutenberg University Mainz
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, PD Dr Markus Möhler, Johannes Gutenberg University Mainz
- Investigators
- Markus Moehler, Prof. Dr. med., Principal investigator, University Medical Center of the Johannes Gutenberg-University Mainz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01679405
- Sponsor's protocol ID
- BIBW 2992
- Status last verified
- Aug 2019
- First submitted
- 17 Aug 2012
- Last updated
- 6 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 30634942
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Uncontrolled, Multicenter Phase I/Ib Trial to Investigate Safety and Efficacy of BIBW 2992 and Standard Gemcitabine/Cisplatin in Chemo-naïve Patients With Advanced Biliary Tract Adenocarcinoma
- ClinicalTrials.gov ID
- NCT01679405
- Acronym / sponsor ID
- BIBW 2992
- Conditions
- Metastatic Disease
- Keywords
- metastatic biliary tract cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No sufficient clinical or molecular signals for efficacy were observed.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Johannes Gutenberg University MainzUniversity, hospital or other
- Study start
- Aug 2012
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 6 Sep 2012 (estimated)
- Results
- Posted 22 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
The primary objective is safety and toxicity, including maximum tolerated dose, of BIBW 2992 when given as add-on therapy to Gem/Cis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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)
| Arm | Type | Receives |
|---|---|---|
| Dose level 1 (Part A) | Experimental | Drug: BIBW 299230 mg BIBW 2992, Gemcitabin (1.000 mg/m² BSA i.v.)/Cisplatin (25 mg/m² BSA i.v.) |
| Dose level -1 (Part A) | Experimental | Drug: BIBW 299230 mg BIBW 2992, Gemcitabin (800 mg/m² BSA i.v.)/Cisplatin (20 mg/m² BSA i.v.) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- 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)
- 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)
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BIBW 2992Also: Gemcitabine and Cisplatinonce daily per os | Drug | Dose level -1 (Part A), Dose level 1 (Part A) |
Primary outcome
Number of Adverse Events
Time frame: Treatment period: up to eight cycles (maximum 8 months). 12 months follow-up period.
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.
4 secondary outcomes
Time to Progress (TTP)
Time frame: Treatment period: up to eight cycles (maximum 8 months). 12 months follow-up period.
Overall Survival (OS)
Time frame: 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
Time frame: Treatment period: up to eight cycles (maximum 8 months).
Tumor Control Rate
Time frame: Treatment period: up to eight cycles (maximum 8 months).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30634942Moehler 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Markus Moehler, Prof. Dr. med. principal investigator
University Medical Center of the Johannes Gutenberg-University Mainz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BIBW 2992 in people with Metastatic Disease, run by Johannes Gutenberg University Mainz at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Adverse Events (time frame: Treatment period: up to eight cycles (maximum 8 months). 12 months follow-up period.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01679405, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2019.