Molecularly Target Therapy With GEMOX in Advanced or Recurrent Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma

Phase 2

• Conditions: Gallbladder Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct
• Interventions: Procedure: biological test; Drug: GEMOX; Drug: Cetuximab; Drug: Trastuzumab; Drug: Gefitinib; Drug: Lapatinib; Drug: Everolimus; Drug: Sorafenib; Drug: Crizotinib

• Registration Number: NCT02836847
• Lead Sponsor: Shanghai Jiao Tong University School of Medicine

Brief Summary

The purpose of this study is to evaluate the feasibility, efficacy and safety of target therapy according to genomic and proteomic profiling combined with GEMOX in advanced or recurrent extrahepatic cholangiocarcinoma and gallbladder carcinoma.

Detailed Description

Genomic profiling studies the deoxyribonucleic acid (DNA) of a tumor to detect genetic changes or abnormalities. immuno-histochemistry tests reveal the abnormal activation status of signal pathways involved in study.These information will be used to recommend target therapy which may be more likely to result in a beneficial response.Patients will receive target anti-tumor agents according to the result of genomic and proteomic profiling.

Study Timeline

• Study Start: 2016-07
• Study First Submitted: 2016-07-13
• Study First Submitted QC: 2016-07-14
• Study First Posted: 2016-07-19
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-04
• Last Update Posted: 2018-05-07
• Primary Completion: 2019-12
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 152

Inclusion Criteria

• Chinese；
• Stable vital signs, KPS≥60;
• Patients have a diagnosis of advanced or recurrent metastatic extrahepatic cholangiocarcinoma or gallbladder carcinoma by histopathology or cytopathology, who are not suitable for radical surgery or have progressed R1 resection or palliative surgery;
• Adequate fresh tumor tissue for genome sequencing and immuno-histochemistry test; harboring mutations or abnormal activation of erb-b2 receptor tyrosine kinase signal pathway components;
• At least one measurable and evaluable site of disease according to the RECIST criteria version 1.1;
• Life expectancy of more than 12 weeks;
• Adequate hepatic, hematologic and renal functions(ALT≤10×upper limit of normal (ULN), AST≤10×ULN, the Child-Pugh classification for class A or B, white blood cells≥3×10^9/L, neutrophils≥1.5×10^9/L, platelets≥80×10^9/L , hemoglobin ≥ 90g/L, creatinine clearance rate≥60ml/min;
• Volunteer for this study, have written informed consent and have good Patient compliance;
• Female patients of childbearing potential and their mates agree to avoid pregnancy.

Exclusion Criteria

• Have received following treatment before this study:

  1. Anti-tumor molecular target therapy; anti-tumor chemotherapy in 6 months;
  2. lesions have been treated by irradiation;
  3. participate in other therapeutic or interventional clinical trials.

• Have central nervous system metastasis;

• History of other malignancies except carcinoma in-situ of uterine cervix, cured basal cell carcinoma of skin and other malignancies for more than 5 years;

• Have symptomatic ascites and need for treatment;

• Have serious concurrent illness including, but not limited to

  1. uncontrolled congestive heart failure(NYHA classification grade III or IV), unstable angina pectoris, unstable cardiac arrhythmias, uncontrolled moderate or serious hypertension(systolic blood pressure >21.3 Kpa or diastolic blood pressure >13.3 Kpa);
  2. ongoing or active serious infection;
  3. uncontrolled diabetes mellitus;
  4. psychiatric illness which potentially hamper the ability to willingly give written informed consent and compliance with the study protocol;
  5. HIV infection;
  6. other serious illness considered not suitable for this study by investigators.

• be allergic or have contraindications to target medicines involved in this study, gemcitabine or oxaliplatin.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GEMOX	biological test	The patients wil receive conventional chemotherapy(GEMOX).
target therapy	GEMOX	The patients wil receive conventional chemotherapy(GEMOX) combined with target agents according to the result of genomic and proteomic profiling of tumor tissue.
target therapy	Cetuximab	The patients wil receive conventional chemotherapy(GEMOX) combined with target agents according to the result of genomic and proteomic profiling of tumor tissue.
target therapy	biological test	The patients wil receive conventional chemotherapy(GEMOX) combined with target agents according to the result of genomic and proteomic profiling of tumor tissue.
GEMOX	GEMOX	The patients wil receive conventional chemotherapy(GEMOX).
target therapy	Sorafenib	The patients wil receive conventional chemotherapy(GEMOX) combined with target agents according to the result of genomic and proteomic profiling of tumor tissue.
target therapy	Crizotinib	The patients wil receive conventional chemotherapy(GEMOX) combined with target agents according to the result of genomic and proteomic profiling of tumor tissue.
target therapy	Trastuzumab	The patients wil receive conventional chemotherapy(GEMOX) combined with target agents according to the result of genomic and proteomic profiling of tumor tissue.
target therapy	Gefitinib	The patients wil receive conventional chemotherapy(GEMOX) combined with target agents according to the result of genomic and proteomic profiling of tumor tissue.
target therapy	Lapatinib	The patients wil receive conventional chemotherapy(GEMOX) combined with target agents according to the result of genomic and proteomic profiling of tumor tissue.
target therapy	Everolimus	The patients wil receive conventional chemotherapy(GEMOX) combined with target agents according to the result of genomic and proteomic profiling of tumor tissue.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	up to 1 year	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year. The progression is defined consistent with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria for solid tumors.

Secondary Outcome Measures

Name	Time	Method
Overall survival	up to 2 years
percentage of patients with Clinical Benefit Response	up to 1 year	Composite measure based on patient-reported pain (per Faces pain scale revised), patient-reported pain medication, Karnofsky performance status(KPS), and weight. Clinical benefit is indicated by either:(a) improvement in pain (less pain intensity with stable or decreased pain medication; or less pain medication with stable or decreased pain intensity) with stable or improved KPS; or (b) improvement in KPS with stable or improved pain.With stable for KPS and pain, clinical benefit may be indicated with an observation of positive weight change.; Clinical benefit response (CBR) was classified weekly and a patient was considered a clinical benefit responder if clinical benefit was observed and maintained over a 4 week period.
Objective Response Rate	up to 1 year	Objective Response Rate is defined as the percentage of patients with a complete or partial response to treatment, consistent with RECIST version 1.1 criteria for solid tumors.
Disease Control Rate	up to 1 year	Disease Control Rate is defined as the percentage of patients with a complete or partial response to treatment or stable disease, consistent with RECIST version 1.1 criteria for solid tumors.

Trial Locations

Locations (1)

Xinhua Hospital; 🇨🇳 Shanghai, Shanghai, China