AdenocarcinomaPhase 2NCT00661830
Gemcitabine and Sorafenib in Advanced Biliary Tract Cancer (GEMSO)
A Phase 2 study testing Gemcitabine and Sorafenib in people with Adenocarcinoma, run by PD Dr Markus Möhler at 11 sites in Germany.
Trial summary
This trial will be conducted to evaluate the efficacy, safety and tolerability of a combination of gemcitabine plus sorafenib in comparison of gemcitabine plus placebo as a first-line palliative therapy in chemo-naive advanced or metastatic CCC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma
- What is being tested?
- Gemcitabine and Sorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- 11 sitesGermany
- Study dates
- May 2008to Jun 2010
- Phase
- Phase 2
- 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 and older
- Signed and dated informed consent before the start of specific protocol procedures
- Adenocarcinoma of the gallbladder or intrahepatic bile ducts or histologically proven hepatic metastases of an earlier resected and histologically proven biliary tract cancer
- Not amenable to curative surgical resection
- With at least one unidimensionally measurable target lesion in non-irradiated (or treated by photodynamic therapy, PDT) area (largest diameter ≥ 1 cm (spiral CT scan or MRI) or ≥ 2 cm (conventional CT scan)
- With pain and biliary obstruction controlled
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- Cytologically or histologically confirmed
- Note : in case of uncertain biliary tract origin (e.g., intrahepatic CCCs), inclusion is possible if
- extensive search for primary tumor (thoracic and abdomino pelvic CT scan, colonoscopy, upper digestive endoscopy, serum PSA level for men or mammography for women, and FDG-PET if possible) is negative
- histological examination is consistent with bile duct adenocarcinoma, with IHC positive for cytokeratin 7 and 19 and negative for cytokeratin 20 [Shimonishi, 2000].
- No histological evidence of hepatocellular carcinoma (HCC)
- No prior palliative (radio)-chemotherapy (gemcitabine or fluoropyrimidine-based chemotherapy)
- Note:
- previous adjuvant chemotherapy is allowed (completed since ≥ 6 months if containing gemcitabine or platinum salts);
- previous irradiation (external radiotherapy, brachytherapy, chemoembolization) and PDT are allowed, provided that there is at least one unidimensionally measurable target lesion in untreated area
- Resolution of all side effects of prior surgical procedures to grade ≤ 1 (except for the laboratory values specified below)
- At least 4 weeks from any major surgery (at first dose of study drug)
- ECOG Performance Status of 0-2
Who cannot join
- Surgery (except diagnostic biopsy), 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. Patients curatively treated and disease free for at least 5 years will be discussed with the sponsor before inclusion
- History of cardiac disease: congestive heart failure > NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
- Any of the following within the 12 months prior to starting the study treatment,: coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
- Ongoing cardiac dysrhythmias of grade ≥ 2, atrial fibrillation of any grade, or QTc interval > 450 msec for males or > 470 msec for females
- Hypertension that cannot be controlled by medications ( > 150/100 mmHg despite optimal medical therapy)
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- History of HIV infection
- Active clinically serious infections ( > grade 2 NCI-CTC version 3.0)
- Known Central Nervous System tumors including metastatic brain disease
- Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
- History of organ allograft
- Patients with evidence or history of bleeding diathesis
- Active disseminated intravascular coagulation, or patients prone to thromboembolism
- Patients undergoing renal dialysis
- Pregnant or breast-feeding patients
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Germany11 sites
Universitätsklinikum Jena, Klinik für Innere Medizin, Innere Medizin II
D-07740 Jena
Universitätsklinikum Hamburg-Eppendorf, I. Med. Klinik, Zentrum für Innere Medizin, Martinistr. 3
D-20248 Hamburg
Klinikum Fulda gAG, Tumorklinik, Pacelliallee 4
D-36043 Fulda
Klinikum der Johann-Wolfgang Goethe-Universität, Innere Medizin I, Theodor-Stern-Kai 7
D-60590 Frankfurt
Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II, Kirrberger Str., Gebäude 41
D-66421 Homburg/Saar
Klinikum der Universität München, Medizinische Klinik II, Marchioninistr. 15
D-81377 München
Klinikum rechts der Isar, TU München, II. Medizinische Klinik und Poliklinik, Ismaningerstr. 22
D-81675 München
II. Med. Klinik, Leopoldina-Krankenhaus der Stadt Schweinfurt, Gustav-Adolf-Str. 8
D-97422 Schweinfurt
Klinikum Esslingen
Esslingen am Neckar, 73730
Universitätsklinikum Halle, Innere Medizin I
Halle, 06120
Klinikum der Johannes Gutenberg-Universität Mainz, I. Med. Klinik
Mainz, Rhineland-Palatinate, 55131
About this study
Official title: A Randomized, Double-blind, Multicenter Phase II Trial With Gemcitabine Plus Sorafenib Versus Gemcitabine Plus Placebo in Patients With Chemo-naive Advanced or Metastatic Adenocarcinoma of the Biliary Tract
This trial will be conducted to evaluate the efficacy, safety and tolerability of a combination of gemcitabine plus sorafenib in comparison of gemcitabine plus placebo as a first-line palliative therapy in chemo-naive advanced or metastatic CCC. There is strong scientific rationale for exploring the role of sorafenib in combination with gemcitabine in advanced CCC.
Sorafenib is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis through blockade of the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGF-R2, R3 and PDGFR-β.
Read more
Mutations in these signaling pathways display by far the most common genetic alterations in CCC and overexpression correlates to poor prognosis. Furthermore, there is no evidence of a consistent or meaningful pharmacokinetic interaction between sorafenib and gemcitabine, suggesting that sorafenib can safely be combined with gemcitabine.
Clinical results of a combination of sorafenib and gemcitabine in a phase I study in pancreatic cancer suggested a therapeutic effect, and the safety and efficacy results together with the knowledge of the molecular pathology of CCC provide a rationale for a randomized, placebo-controlled phase II trial consisting of gemcitabine plus sorafenib in advanced CCC.
- Conditions
- Adenocarcinoma
- Being tested
- Gemcitabine, Placebo, Sorafenib
- Keywords
- advanced, metastatic, biliary, tract
- Medical subject headings
- Adenocarcinoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Gemcitabine 1000 mg/m2 body surface i.v. first cycle at day 1, 8, 15, 22, 29, 36, 43. Next cycles at day 1, 8, 15.
PlaceboDrug
Placebo
SorafenibDrug
Sorafenib 400 mg bid orally continuously
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Gemcitabine + Sorafenib Receives: Drug: Gemcitabine; Drug: Sorafenib |
| 2 | Placebo comparator | Gemcitabine + Placebo Receives: Drug: Gemcitabine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
The primary endpoint is the progression-free survival (PFS) defined as the time from start of treatment to first documentation of objective tumor progression or to death due to any cause, whichever occurs first during treatment or follow-up period. For patients not known to have died as of the data cut-off date and who do not have objective progressive disease, PFS will be censored at the date of the last objective progression-free disease assessment. For patients who receive subsequent anticancer therapy (after discontinuation from the study drug) prior to objectively determined disease progression or death, PFS will be censored at the date of the last objective progression-free disease assessment prior to post-discontinuation anti-cancer therapy. Acceptable documentation of objective disease progression status consists of objective assessments using CT scan assessment method.
Measured: one year
Secondary outcomes (3)
Overall Survival
Overall Survival (OS) is measured from start of treatment to death due to any cause until end of follow-up period. Time to last observation will be used if a patient has not died and OS for the patient will be considered censored at the date of the last observation.
Measured: one year
Best Overall Response
Best Overall Response (BOR) is defined as the best tumor response (confirmed partial or complete response, stable disease) that is achieved during treatment or within 30 days after termination of active therapy that is confirmed according to the RECIST tumor response criteria. Best response is determined from the sequence of responses assessed. For complete response (CR) or partial response (PR), best response must be confirmed by a second assessment within 4 -6 weeks.
Two objective status determinations of CR before progression are required for a best response of CR.
Two determinations of PR or better before progression, but not qualifying for a CR, are required for a best response of PR.
Best response of Stable Disease (SD) is defined as disease that does not meet the criteria of CR, PR or Progressive Disease (PD) and has been evaluated at least one time, at least 6 weeks after baseline assessment.
Measured: one year
Time to Objective Response
Time to Objective Response (OR) is defined as the time from start of treatment to objective tumor response (CR or PR) is first documented according to the RECIST tumor response criteria during treatment or until 30 days after termination of active therapy. Response must subsequently be confirmed. For subjects failing to achieve an objective response and who did not progress during the trial, time to objective response will be censored at their last date of tumor evaluation.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2008 (estimated)
- Study startMay 2008
- Primary completionJun 2010
- Study completionJun 2010
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 AdenocarcinomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- PD Dr Markus Möhler
- Sponsor type
- University, hospital or other
- Collaborators
- Johannes Gutenberg University Mainz, Interdisciplinary Center for Clinical Trials (IZKS)
- Responsible party
- Sponsor-investigator, PD Dr Markus Möhler, Johannes Gutenberg University Mainz
- Investigators
- Markus Moehler, MD, Principal investigator, Johannes Gutenberg University Mainz, I. Med. Klinik
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00661830
- Sponsor's protocol ID
- CC-GEMSO-2007
- Status last verified
- Sep 2013
- First submitted
- 15 Apr 2008
- Last updated
- 21 Nov 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Kaps L, Genc MA, Moehler M, Grabbe S, Schattenberg JM, Schuppan D, Pedersen RS, Karsdal MA, Mildenberger P, Maderer A, Willumsen N. Collagen turnover biomarkers to predict outcome of patients with biliary cancer. BMC Gastroenterol. 2025 Feb 4;25(1):53. doi: 10.1186/s12876-025-03645-0.
PubMed 39905306
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Multicenter Phase II Trial With Gemcitabine Plus Sorafenib Versus Gemcitabine Plus Placebo in Patients With Chemo-naive Advanced or Metastatic Adenocarcinoma of the Biliary Tract
- ClinicalTrials.gov ID
- NCT00661830
- Acronym / sponsor ID
- CC-GEMSO-2007
- Conditions
- Adenocarcinoma
- Keywords
- advanced, metastatic, biliary, tract
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- PD Dr Markus MöhlerUniversity, hospital or other
- Collaborators
- Johannes Gutenberg University Mainz, Interdisciplinary Center for Clinical Trials (IZKS)
- Study start
- May 2008
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 18 Apr 2008 (estimated)
- Results
- Posted 21 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial will be conducted to evaluate the efficacy, safety and tolerability of a combination of gemcitabine plus sorafenib in comparison of gemcitabine plus placebo as a first-line palliative therapy in chemo-naive advanced or metastatic CCC. There is strong scientific rationale for exploring the role of sorafenib in combination with gemcitabine in advanced CCC.
Sorafenib is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis through blockade of the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGF-R2, R3 and PDGFR-β.
Mutations in these signaling pathways display by far the most common genetic alterations in CCC and overexpression correlates to poor prognosis. Furthermore, there is no evidence of a consistent or meaningful pharmacokinetic interaction between sorafenib and gemcitabine, suggesting that sorafenib can safely be combined with gemcitabine.
Clinical results of a combination of sorafenib and gemcitabine in a phase I study in pancreatic cancer suggested a therapeutic effect, and the safety and efficacy results together with the knowledge of the molecular pathology of CCC provide a rationale for a randomized, placebo-controlled phase II trial consisting of gemcitabine plus sorafenib in advanced CCC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Gemcitabine, Drug: SorafenibGemcitabine + Sorafenib |
| 2 | Placebo comparator | Drug: Gemcitabine, Drug: PlaceboGemcitabine + Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Male and female patients aged 18 years and older
- Signed and dated informed consent before the start of specific protocol procedures
- Adenocarcinoma of the gallbladder or intrahepatic bile ducts or histologically proven hepatic metastases of an earlier resected and histologically proven biliary tract cancer
- Note : in case of uncertain biliary tract origin (e.g., intrahepatic CCCs), inclusion is possible if
- Note:
Key exclusion criteria (15 listed)
- Surgery (except diagnostic biopsy), 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. Patients curatively treated and disease free for at least 5 years will be discussed with the sponsor before inclusion
- History of cardiac disease: congestive heart failure > NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
- Any of the following within the 12 months prior to starting the study treatment,: coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
- Ongoing cardiac dysrhythmias of grade ≥ 2, atrial fibrillation of any grade, or QTc interval > 450 msec for males or > 470 msec for females
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 |
|---|---|---|
| GemcitabineGemcitabine 1000 mg/m2 body surface i.v. first cycle at day 1, 8, 15, 22, 29, 36, 43. Next cycles at day 1, 8, 15. | Drug | 1, 2 |
| PlaceboPlacebo | Drug | 2 |
| SorafenibSorafenib 400 mg bid orally continuously | Drug | 1 |
Primary outcome
Progression-free Survival (PFS)
Time frame: one year
The primary endpoint is the progression-free survival (PFS) defined as the time from start of treatment to first documentation of objective tumor progression or to death due to any cause, whichever occurs first during treatment or follow-up period. For patients not known to have died as of the data cut-off date and who do not have objective progressive disease, PFS will be censored at the date of the last objective progression-free disease assessment. For patients who receive subsequent anticancer therapy (after discontinuation from the study drug) prior to objectively determined disease progression or death, PFS will be censored at the date of the last objective progression-free disease assessment prior to post-discontinuation anti-cancer therapy. Acceptable documentation of objective disease progression status consists of objective assessments using CT scan assessment method.
3 secondary outcomes
Overall Survival
Time frame: one year
Best Overall Response
Time frame: one year
Time to Objective Response
Time frame: one year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39905306Kaps L, Genc MA, Moehler M, Grabbe S, Schattenberg JM, Schuppan D, Pedersen RS, Karsdal MA, Mildenberger P, Maderer A, Willumsen N. Collagen turnover biomarkers to predict outcome of patients with biliary cancer. BMC Gastroenterol. 2025 Feb 4;25(1):53. doi: 10.1186/s12876-025-03645-0.
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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, MD principal investigator
Johannes Gutenberg University Mainz, I. Med. Klinik
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gemcitabine and Sorafenib in people with Adenocarcinoma, run by PD Dr Markus Möhler at 11 sites 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 18 inclusion and 15 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: finished, as of the sponsor's last update on 21 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 21 Nov 2013). 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?
Progression-free Survival (PFS) (time frame: one year). 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 NCT00661830, 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 21 Nov 2013.