Addition of Everolimus to Standard of Care in Carcinoma Gallbladder

Sponsor

Banaras Hindu University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05833815

Collaborator

(none)

Enrollment

Location

Arms

12.9

Anticipated Duration (Months)

4.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Gallbladder Cancer	Drug: Everolimus 10 mg Drug: Standard of care	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

56 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 1, 2022

Anticipated Primary Completion Date :

Nov 30, 2023

Anticipated Study Completion Date :

Nov 30, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Progression free survival [12 months]
Progression free survival from diagnosis to disease progression or death

Secondary Outcome Measures

Overall survival [24 months followup]
Survival time from the enrollment till the study closure
Chemotherapy Toxicity [12 months]
Toxicity of addition of Everolimus to standard of care as measured by WHO toxicity criteria

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banaras Hindu University	Varanasi	UP	India	221010

Sponsors and Collaborators

Banaras Hindu University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Manoj Pandey, Professor, Banaras Hindu University

ClinicalTrials.gov Identifier:

NCT05833815

Other Study ID Numbers:

GBC01

First Posted:

Apr 27, 2023

Last Update Posted:

Apr 27, 2023

Last Verified:

Apr 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Manoj Pandey, Professor, Banaras Hindu University

everolimus

mToR inhibitors

chemotherapy

Additional relevant MeSH terms:

Gallbladder Neoplasms

Everolimus

Study Results

No Results Posted as of Apr 27, 2023