Addition of Everolimus to Standard of Care in Carcinoma Gallbladder

NCT05833815 | Recruiting Phase 2 DMC

• 1 other identifier: GBC01
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Gallbladder Cancer

Keywords

everolimus; mToR inhibitors; chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression free survival from diagnosis to disease progression or death

  12 months

Secondary Outcomes (2)

• Overall survival

  24 months followup

• Chemotherapy Toxicity

  12 months

Study Arms (2)

Additional Everolimus

EXPERIMENTAL

Everolimus 10 mg. PO/day in addition to standard of care

Drug: Everolimus 10 mg

Control

OTHER

Standard of care alone i.e Capecitabine and Oxaliplatin or Gemcitabine and oxaliplatin

Drug: Standard of care

Interventions

Everolimus 10 mg DRUG

Oral Everolimus 10 mg daily in addition to standard of care i.e. GemOx or CapOx

Also known as: CapOx/GemOx

Additional Everolimus

Standard of care DRUG

GemOx or CapOx

Also known as: Chemotherapy

Control

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Banaras Hindu University: lead

Study Sites (1)

Banaras Hindu University

Varanasi, Uttar Pradesh, 221010, India

RECRUITING

Related Publications (6)

• Eckel F, Schmid RM. Chemotherapy and targeted therapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Chemotherapy. 2014;60(1):13-23. doi: 10.1159/000365781. Epub 2014 Oct 21.

  PMID: 25341559 BACKGROUND

• Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.

  PMID: 20375404 BACKGROUND

• O'Donnell A, Faivre S, Burris HA 3rd, Rea D, Papadimitrakopoulou V, Shand N, Lane HA, Hazell K, Zoellner U, Kovarik JM, Brock C, Jones S, Raymond E, Judson I. Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors. J Clin Oncol. 2008 Apr 1;26(10):1588-95. doi: 10.1200/JCO.2007.14.0988. Epub 2008 Mar 10.

  PMID: 18332470 BACKGROUND

• Primrose JN, Fox RP, Palmer DH, Malik HZ, Prasad R, Mirza D, Anthony A, Corrie P, Falk S, Finch-Jones M, Wasan H, Ross P, Wall L, Wadsley J, Evans JTR, Stocken D, Praseedom R, Ma YT, Davidson B, Neoptolemos JP, Iveson T, Raftery J, Zhu S, Cunningham D, Garden OJ, Stubbs C, Valle JW, Bridgewater J; BILCAP study group. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019 May;20(5):663-673. doi: 10.1016/S1470-2045(18)30915-X. Epub 2019 Mar 25.

  PMID: 30922733 BACKGROUND

• Ben-Josef E, Guthrie KA, El-Khoueiry AB, Corless CL, Zalupski MM, Lowy AM, Thomas CR Jr, Alberts SR, Dawson LA, Micetich KC, Thomas MB, Siegel AB, Blanke CD. SWOG S0809: A Phase II Intergroup Trial of Adjuvant Capecitabine and Gemcitabine Followed by Radiotherapy and Concurrent Capecitabine in Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma. J Clin Oncol. 2015 Aug 20;33(24):2617-22. doi: 10.1200/JCO.2014.60.2219. Epub 2015 May 11.

  PMID: 25964250 BACKGROUND

• Graham JS, Boyd K, Coxon FY, Wall LR, Eatock MM, Maughan TS, Highley M, Soulis E, Harden S, Butzberger-Zimmerli P, Evans TR. A phase II study of capecitabine and oxaliplatin combination chemotherapy in patients with inoperable adenocarcinoma of the gall bladder or biliary tract. BMC Res Notes. 2016 Mar 12;9:161. doi: 10.1186/s13104-015-1778-4.

  PMID: 26969121 BACKGROUND

MeSH Terms

Conditions

Gallbladder Neoplasms

Interventions

Everolimus; Standard of Care; Drug Therapy

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Therapeutics

Central Study Contacts

Manoj Pandey

CONTACT

+91-542-2369332; mpandey66@bhu.ac.in

Madhumita Tripathi

CONTACT

mishthi2018@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: April 27, 2023
• Study Start: November 1, 2022
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: August 13, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)