Addition of Everolimus to Standard of Care in Carcinoma Gallbladder

April 18, 2023 updated by: Manoj Pandey, Banaras Hindu University

A Randomized Controlled, Open Labeled, Two Arm, Study of Addition of Everolimus to Standard of Care in Carcinoma Gallbladder

Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract. It is also the most aggressive cancer of the biliary tract with the shortest median survival from the time of diagnosis. Currently, radical resection is the most effective strategy to potentially cure GBC. Chemotherapy and radiotherapy have been employed as adjuvant and palliative setting, however, the overall survival is still dismal. This study aim to evaluate the addition of Everolimus in addition to standard of care in gallbladder cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Gallbladder cancer is the most common malignant tumour of the biliary tract. It is also the most aggressive cancer of the biliary tract with the shortest median survival from the time of diagnosis. While the incidence rate of GBC varies widely, it has a unique distribution pattern in some regions, where Chile, India, some other Asian countries, Eastern European, and Latin American countries have reported more cases than the rest of the world every year. The other factors, which associated with chronic inflammation and disease pathogenesis, such as hepatobiliary stones, liver flukes, and Salmonella frequently observed in these areas, also constitute the other high-risk factors of bile tract cancer (BTC) including GBC.

Currently, radical resection is the most effective strategy to potentially cure GBC. The non-surgical therapies engaged in patients were primarily composed of chemotherapy and radiotherapy. additional therapeutic strategies including next-generation sequencing (NGS), whole-exome sequencing (WES), RNA-sequencing (RNAseq), and single-cell isolation, as well as characterization that have fundamentally opened a novel view enabled to globally identify genetic and epigenetic features and key molecules as potential therapeutic target.

Advanced or unrespectable locally advanced disease has a poor prognosis with limited systemic treatment options. Combination platinum-gemcitabine chemotherapy is an active first-line treatment regimen.in particular, specific target treatment, immune therapy, vaccine therapy, biotherapy and nanoparticles have been intensively developed in preclinical and clinical trials.

One of target treatment is Mammalian target of rapamycin (mTOR) inhibitors, as The mTOR signaling pathway has critical roles in mammalian metabolism and physiology. The de-regulated activity of mTOR is involved in many pathophysiological conditions, such as aging, Alzheimer's disease, diabetes, obesity, and cancer.

Everolimus is a derivative of rapamycin that selectively inhibits mTORC1 (mammalian target of rapamycin complex 1), a key protein kinase complex which regulates cell growth, proliferation and survival. Activation of mTORC1 is mediated by the phosphatidylinositol 3-kinase (PI3K) pathway through activation of AKT/ PKB and subsequent inhibition of the tuberous sclerosis complex.

Study Type

Interventional

Enrollment (Anticipated)

56

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • India
    • UP
      • Varanasi, UP, India, 221010

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histological proof of cancer with stage III inoperable or Stage IV metastatic disease without any prior treatment.
  • Patients with histologic proof of metastatic gallbladder carcinoma who have not had previous treatment for metastatic disease or who received gemcitabine/capecitabine with or without platinum>= 6 months ago as part of adjuvant therapy
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Platelet (PLT) >= 100,000/uL
  • Total bilirubin =< 3mg/dl for gemcitabine and any value for Capecitabine
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN) (=< 5x ULN in patients with liver metastases)
  • Creatinine =< 1.5 x Institutional ULN
  • Alkaline phosphatase =< 5 x Institutional ULN
  • Haemoglobin (Hgb) >= 8.0 g/dL
  • International normalized ratio (INR) and Partial thromboplastin time (PTT) =< 3.0 x ULN (anticoagulation is allowed if target INR =< 3.0 x ULN on a stable dose of warfarin or on a stable dose of low-molecular-weight [LMW] heparin for > 2 weeks at time of registration)
  • Fasting serum glucose < 1.5 x ULN
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2
  • Ability to provide informed consent
  • Willingness to return for follow up
  • Life expectancy >= 12 weeks
  • Women of childbearing potential only: Negative serum pregnancy test done =< 7 days prior to registration.

Exclusion Criteria:

  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Clinically significant cardiac disease, especially history of myocardial infarction =< 6 months, or congestive heart failure (New York Heart Association [NYHA] classification III or IV) requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Patients taking strong inhibitors or inducers of CYP3A4
  • Prior therapy with everolimus

  • Any of the following prior therapies:

    • Chemotherapy =< 4 weeks prior to registration
    • Immunotherapy =< 4 weeks prior to registration
    • Biological therapy =< 4 weeks prior to registration
    • Radiation therapy =< 4 weeks prior to registration
    • Radiation to > 25% of bone marrow prior to registration
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • CNS metastases brain or leptomeningeal metastases that are not stable for at least 4 weeks prior to registration based on imaging, clinical assessment, and use of steroids
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive
  • Current active other malignancy, Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Severely impaired lung function (i.e., forced expiratory volume in one second [FEV1] < 1 liter)
  • Received immunization with attenuated live vaccines =< 7 days prior to study entry or during study period; close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus; examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid, SARS CoV2 vaccines
  • Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C); A detailed assessment of Hepatitis B/C medical history and risk factors will be done at screening for all patients; hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Additional Everolimus
Everolimus 10 mg. PO/day in addition to standard of care
Drug: Everolimus 10 mg
Oral Everolimus 10 mg daily in addition to standard of care i.e. GemOx or CapOx
Other Names:
  • CapOx/GemOx
Other: Control
Standard of care alone i.e Capecitabine and Oxaliplatin or Gemcitabine and oxaliplatin
Drug: Standard of care
GemOx or CapOx
Other Names:
  • Chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 12 months
Progression free survival from diagnosis to disease progression or death
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 24 months followup
Survival time from the enrollment till the study closure
24 months followup
Chemotherapy Toxicity
Time Frame: 12 months
Toxicity of addition of Everolimus to standard of care as measured by WHO toxicity criteria
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Banaras Hindu University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2022

Primary Completion (Anticipated)

November 30, 2023

Study Completion (Anticipated)

November 30, 2023

Study Registration Dates

First Submitted

March 21, 2023

First Submitted That Met QC Criteria

April 18, 2023

First Posted (Actual)

April 27, 2023

Study Record Updates

Last Update Posted (Actual)

April 27, 2023

Last Update Submitted That Met QC Criteria

April 18, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GBC01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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