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

• ClinicalTrials.gov Identifier: NCT02836847
• Recruitment Status: Unknown
• First Posted: July 19, 2016
• Last Update Posted: May 7, 2018
• Sponsor: Shanghai Jiao Tong University School of Medicine
• Collaborators: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital; RenJi Hospital; Eastern Hepatobiliary Surgery Hospital; Huashan Hospital
• Information provided by (Responsible Party): liu yingbin, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cholangiocarcinoma of the Extrahepatic Bile Duct; Gallbladder Cancer	Procedure: biological test; Drug: GEMOX; Drug: Cetuximab; Drug: Trastuzumab; Drug: Gefitinib; Drug: Lapatinib; Drug: Everolimus; Drug: Sorafenib; Drug: Crizotinib	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicentre, Open-label, Randomised, Controlled Study of Molecularly Precision Target Therapy Based on Tumor Molecular Profiling With GEMOX in Advanced or Recurrent Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma
• Study Start Date: July 2016
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: target therapy; The patients wil receive conventional chemotherapy(GEMOX) combined with target agents according to the result of genomic and proteomic profiling of tumor tissue.	Procedure: biological test; mutation and signal pathway activation status analysis; Drug: GEMOX; Conventional chemotherapy:gemcitabine and oxaliplatin; Drug: Cetuximab; Drug: Trastuzumab; Drug: Gefitinib; Drug: Lapatinib; Drug: Everolimus; Drug: Sorafenib; Drug: Crizotinib
GEMOX; The patients wil receive conventional chemotherapy(GEMOX).	Procedure: biological test; mutation and signal pathway activation status analysis; Drug: GEMOX; Conventional chemotherapy:gemcitabine and oxaliplatin

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival [ Time Frame: 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 :

1. Overall survival [ Time Frame: up to 2 years ]
2. Objective Response Rate [ Time Frame: 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.
3. Disease Control Rate [ Time Frame: 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.
4. percentage of patients with Clinical Benefit Response [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: liu yingbin, PHD; +86 13918803900; laoniulyb@163.com

Locations

China, Shanghai

Xinhua Hospital; Recruiting

Shanghai, Shanghai, China, 200092

Contact: yingbin liu 13918803900 laoniulyb@163.com

Sponsors and Collaborators

Shanghai Jiao Tong University School of Medicine

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Ruijin Hospital

RenJi Hospital

Eastern Hepatobiliary Surgery Hospital

Huashan Hospital

Investigators

• Principal Investigator: liu yingbin, PHD; Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

More Information

• Responsible Party: liu yingbin, head of general surgery department，xin hua Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• ClinicalTrials.gov Identifier: NCT02836847
• Other Study ID Numbers: DLY201507
• First Posted: July 19, 2016
• Last Update Posted: May 7, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Cholangiocarcinoma; Gallbladder Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases; Trastuzumab; Cetuximab; Everolimus; Sorafenib; Lapatinib; Gefitinib; Crizotinib; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action