Gemcitabine and Sorafenib in Advanced Biliary Tract Cancer (GEMSO)

NCT00661830 | Completed Phase 2 Results

• 1 other identifier: CC-GEMSO-2007
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 11

Brief 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. 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.

Conditions

Adenocarcinoma

Keywords

advanced; metastatic; biliary; tract

Outcome Measures

Primary Outcomes (1)

• 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.

  one year

Secondary Outcomes (3)

• Overall Survival

  one year

• Best Overall Response

  one year

• Time to Objective Response

  one year

Study Arms (2)

1

EXPERIMENTAL

Gemcitabine + Sorafenib

Drug: Gemcitabine; Drug: Sorafenib

2

PLACEBO COMPARATOR

Gemcitabine + Placebo

Drug: Gemcitabine; Drug: Placebo

Interventions

Gemcitabine DRUG

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.

1; 2

Placebo DRUG

Placebo

2

Sorafenib DRUG

Sorafenib 400 mg bid orally continuously

1

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 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
• Cytologically or histologically confirmed
• 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)

You may not qualify if:

• Surgery (except diagnostic biopsy), external radiotherapy, brachytherapy, or PDT within 30 days prior to start of treatment.
• 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)
• 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

Sponsors & Collaborators

• PD Dr Markus Möhler: lead
• Johannes Gutenberg University Mainz: collaborator
• Interdisciplinary Center for Clinical Trials (IZKS): collaborator

Study Sites (11)

Klinikum der Johannes Gutenberg-Universität Mainz, I. Med. Klinik

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Universitätsklinikum Jena, Klinik für Innere Medizin, Innere Medizin II

D-07740 Jena, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, I. Med. Klinik, Zentrum für Innere Medizin, Martinistr. 3

D-20248 Hamburg, Germany

Location

Klinikum Fulda gAG, Tumorklinik, Pacelliallee 4

D-36043 Fulda, Germany

Location

Klinikum der Johann-Wolfgang Goethe-Universität, Innere Medizin I, Theodor-Stern-Kai 7

D-60590 Frankfurt, Germany

Location

Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II, Kirrberger Str., Gebäude 41

D-66421 Homburg/Saar, Germany

Location

Klinikum der Universität München, Medizinische Klinik II, Marchioninistr. 15

D-81377 München, Germany

Location

Klinikum rechts der Isar, TU München, II. Medizinische Klinik und Poliklinik, Ismaningerstr. 22

D-81675 München, Germany

Location

II. Med. Klinik, Leopoldina-Krankenhaus der Stadt Schweinfurt, Gustav-Adolf-Str. 8

D-97422 Schweinfurt, Germany

Location

Klinikum Esslingen

Esslingen am Neckar, 73730, Germany

Location

Universitätsklinikum Halle, Innere Medizin I

Halle, 06120, Germany

Location

Related Publications (1)

• 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.

  PMID: 39905306 DERIVED

MeSH Terms

Conditions

Adenocarcinoma; Neoplasm Metastasis

Interventions

Gemcitabine; Sorafenib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Results Point of Contact

• Title: A. Kaiser
• Organization: Interdisciplinary Center for Clinical Trials (IZKS Mainz)

kaiser@izks-mainz.de

++49(0)6131-179921

Study Officials

• Markus Moehler, MD

  Johannes Gutenberg University Mainz, I. Med. Klinik

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 15, 2008
• First Posted: April 18, 2008
• Study Start: May 1, 2008
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: November 21, 2013
• Results First Posted: November 21, 2013

Record last verified: 2013-09

Locations

DE (11)