Neoadjuvant Therapy in Biliary Adenocarcinoma

NCT04480190 | Withdrawn Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: UCCC-GI-20-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Feasibility of neoadjuvant therapy in resectable biliary adenocarcinoma.

Conditions

Cholangiocarcinoma; Biliary Cancer

Outcome Measures

Primary Outcomes (1)

• Completion of all therapy. Defined as completing 4/6 doses of gem/cis chemo, 80% of RT dose, and surgical resection.

  Feasibility trial with accrual goal of 12 patients using primary endpoint of completion of neoadjuvant therapy and surgery as an assessment of feasibility. Interim assessment of first 6 patients enrolled will be performed. Resection rate benchmark for neoadjuvant pancreas trials \~70% accounting for patients found to have progression. Completion of all therapy is defined as completing 4/6 doses of gem/cis chemo, 80% of RT dose, and surgical resection. If 2 or less of first 6 patients enrolled complete all therapy the trial will be closed and treatment will be considered unfeasible. Upon trial completion, if 5 or less of 12 patients complete all therapy the trial will be deemed unfeasible.

  5 years

Secondary Outcomes (6)

• Patients will be evaluated for toxicity during protocol therapy and postoperatively using the CTCAE v 5 criteria.

  5 years

• Margin negative resection rate. This will be measured by the Proportion of patients with involved surgical margins (R1 rate).

  5 years

• Lymph node involvement. This will be measured by the Proportion of patients with involved lymph nodes (N0 vs N1).

  5 years

• Survival outcomes measured by Disease Free Survival [DFS])

  5 years

• Survival outcomes measured by Local Failure Free Survival [LFFS].

  5 years

Study Arms (1)

Research Treatment

EXPERIMENTAL

Gemcitabine/Cisplatin/ChemoRT

Drug: Gemcitabine; Drug: Cisplatin; Drug: Fluorouracil; Radiation: Short course ChemoRT

Interventions

Gemcitabine DRUG

IV Gemcitabine 1000mg/m2 to be given on Days 1, Day 8 (Before Cisplatin); 3 week cycles

Also known as: Gemzar

Research Treatment

Cisplatin DRUG

IV Cisplatin 25mg/m2 to be given on Days 1, Day 8

Also known as: Platinol

Research Treatment

Fluorouracil DRUG

Infusional 5-FU 225 mg/m2/d via Continuous IV infusion, to be given Days 1-5 and 8-12 during RT

Also known as: 5FU

Research Treatment

Short course ChemoRT RADIATION

Radiation Therapy: Sim: All patients will undergo 4D-CT simulation with 3 hours fasting with or without IV contrast. Compression may be used depending on the tumor motion. Radiation Target Volume: The gross tumor volume (GTV) will be defined on all relevant imaging datasets including diagnostic CT, MRI, MRCP and/or ERCP data. An iGTV will be generated using the 4D datasets. The clinical target volume (CTV) will include the entire iGTV as well as portal lymphatic and celiac nodal space for all patients with selective treatment of the SMA and pancreaticoduodenal depending on the tumor location. A 5 mm margin will be added to the CTV to generate the planning target volume (PTV). Radiation Dose: The dose will be 30 Gy in 10 fractions (3 Gy per fraction) for all patients using either 3D Conformal or Intensity Modulated Radiation Therapy techniques.

Also known as: ChemoRT

Research Treatment

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• ECOG performance status ≤2
• Patients must have adequate organ and marrow function as defined below:
• leukocytes ≥3,000/mcL absolute neutrophil count ≥1,500/mcL platelets ≥100,000/mcL total bilirubin ≤ 7 AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN creatinine ≤ institutional ULN OR glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2
• Known human immunodeficiency virus (HIV)-infected patients must be on effective anti-retroviral therapy with undetectable viral load within 6 months to be eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Patients must have either biopsy proven biliary adenocarcinoma (Intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, extrahepatic cholangiocarcinoma), or Gallbladder Adenocarcinoma or cytology with FISH abnormality sufficient for diagnosis.
• Patients must be deemed to have tumor that is resectable by the surgical oncologist and must have no medical contraindications to surgery.
• All patients must have a CT scan of the chest, abdomen, and pelvis with contrast or PET scan demonstrating no evidence of metastatic disease within 6 weeks prior to protocol therapy.
• Patients with enlarged regional lymph nodes within the dissection basin are eligible for participation.
• Women of child-bearing potential and men must agree to use adequate contraception for 14 months (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 14 months after completion.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients with metastatic disease on imaging (biopsy not required).
• Patients not eligible for surgery due to tumor anatomy or medical comorbidities.
• Patients with known hypersensitivity to cisplatin, gemcitabine or 5-FU or any component of the formulation.
• Patients who have had chemotherapy or radiotherapy within 3 months prior to entering the study.
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
• Patients who are currently receiving any other investigational agents are excluded. Patients who received investigational agents prior to consenting to participate on this study who are no longer currently receiving those agents, are eligible.
• Patients with uncontrolled intercurrent illness that would prevent receipt of standard of care chemotherapy, radiation or surgery.
• Patients with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study.

Sponsors & Collaborators

• Jordan Kharofa: lead

Study Sites (1)

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Biliary Tract Neoplasms

Interventions

Gemcitabine; Cisplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones

Study Officials

• Jordan Kharofa, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 25, 2020
• First Posted: July 21, 2020
• Study Start: February 4, 2021
• Primary Completion: April 4, 2022
• Study Completion: April 4, 2022
• Last Updated: April 20, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)