E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
unresecable, metastatic or recurrent cholangiocarcinoma (intrahepatic cholangiocellular carcinoma, bile duct cancer, gall bladder carcinoma) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008594 |
E.1.2 | Term | Cholangiocarcinoma non-resectable |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective:
To determine the efficacy of Gemcitabine/nab-Paclitaxel in first-line therapy of patients with cholangiocarcinoma ineligible for Cisplatin-based therapy. Results of the first 10 evaluable patients will be compared to patient outcomes from the cancer registry of the West German Cancer Center (patients treated with Gemcitabine-combinations, patients treated with monotherapies). Primary endpoint will be overall response rate (ORR) (complete remission and partial remission)
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E.2.2 | Secondary objectives of the trial |
Secondary objectives:
Disease control rate (DCR) (complete remission, partial remission and stable disease for at least 8 weeks) (estimated 80%)*
Progression free survival (PFS) (estimated 8 months)*
PFS rate at 6 months (estimated 60%)*
Overall survival (OS) (estimated 12 months)*
Serological response (decrease in CA19-9 levels)
Toxicity/safety
Quality of life (QoL)
Translational: correlation of tumor response with SPARC expression in tumor and stroma; mutational status of key oncogenes
Tumor samles will be stored für subsequent analyses, if study is positive
*based on the combination cisplatin/gemcitabine (Valle et al., 2010)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
signed informed consent before start of specific protocol procedure
age > 18 years
histologically or cytologically documented diagnosis of cholangiocellular carcinoma, bile duct cancer or gall bladder carcinoma
presence of at least one measurable site of disease following RECIST 1.1 criteria
unresecable, metastatic or recurrent disease
ECOG performance 0 or 1
life expectancy of at least 3 months
any contraindication for Cisplatin, i.e. renal impairment (creatinine clearance < 60 ml/min), impaired hearing, increased risk or history for thromboembolic events, intolerance of extensive hydration, left ventricular ejection fraction (LVEF) < 45%
adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening
absolute neutrophil count (ANC) ≥ 1500/μl
platelet count ≥ 100,000/µl
total bilirubin < 3 x ULN and sufficient biliary drainage
ALT and AST < 3 x ULN, < 5 x ULN if liver metastasis present
PT-INR/PTT < 1.5 x ULN, patients therapeutically anticoagulated with NMH, heparin or NOACs (dabigatran, rivaroxaban, abixaban) are allowed to participate, patients anticoagulated with phenoprocoumon or warfarin should be switched to NMH, heparin or NOACs
creatinine clearance ≥ 30ml/min and serum creatinine ≤ 2.5 x ULN
confirmed menopause, negative pregnancy test within 7 days of the start of treatment and willingness to use highly effective methods of contraception
willingness and able to comply with the protocol for the duration of the study
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E.4 | Principal exclusion criteria |
no prior anti-cancer chemotherapy or radiotherapy for metastatic, advanced or recurrent disease; adjuvant/additive chemotherapy or radiotherapy after resection is allowed if therapy free intervall is at least 4 months; concomitant small volume palliative radiotherapy of bone metastases are allowed
investigational drug therapy during or within 4 weeks of study entry
major surgery within 4 weeks of starting therapy within this study
symptomatic brain metastasis
clincially significant cardiovascular disease (incl. Myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrollment
active clinically serious infections (> grade 2 NCI-CTC version 4.0)
history of interstitial lung disease
liver cirrhosis child-pugh score > 8
history of HIV infection or chronic hepatitis B or C
pre-exisiting neuropathy > grade 1 (NCI-CTC version 4.0)
patients with evidence of bleeding diathesis
patients with second primary cancer within 5 years, exept adequately treated basal skin cancer or carcinoma in-situ of the cervix or bladder, or low/intermediate risk prostate cancer (Gleason score ≤ 7) with normal PSA levels
any condition that could jeopardize the safety of the patient and their compliance of the study
breast-feeding patients
substance abuse, medical, psychological or social conditions that may interfere with the participation in the study
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E.5 End points |
E.5.1 | Primary end point(s) |
overall response rate (ORR) (complete remission and partial remission) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Disease control rate (DCR) (complete remission, partial remission and stable disease for at least 8 weeks) (estimated 80%)*
Progression free survival (PFS) (estimated 8 months) PFS rate at 6 months (estimated 60%)*
Overall survival (OS) (estimated 12 months)*
Serological response (decrease in CA19-9 levels)
Toxicity/safety
Quality of life (QoL)
Translational: correlation of tumor response with SPARC expression in tumor and stroma; mutational status of key oncogenes
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |