Clinical trial NCT04480190: Neoadjuvant Therapy in Biliary Adenocarcinoma
Official title: Feasibility of Total Neoadjuvant Therapy in Resectable Biliary Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Cholangiocarcinoma
Biliary Cancer
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
First posted: 2020-07-21
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Feasibility of neoadjuvant therapy in resectable biliary adenocarcinoma.

Detailed description: This trial will evaluate whether a neoadjuvant paradigm is feasible in resectable biliary adenocarcinoma. All components of therapy are currently used standards of care, however they have not been used in the neoadjuvant setting for the management of resectable biliary cancers. The study will use Gemcitabine/cisplatin, followed by chemoradiation.

This is a feasibility trial with an accrual goal of 12 patients using the primary endpoint of completion of neoadjuvant therapy and surgery as an assessment of feasibility.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Completion of all therapy. Defined as completing 4/6 doses of gem/cis chemo, 80% of RT dose, and surgical resection.
timeFrame: 5 years
Secondary outcomes:
measure: Patients will be evaluated for toxicity during protocol therapy and postoperatively using the CTCAE v 5 criteria.
timeFrame: 5 years
measure: Margin negative resection rate. This will be measured by the Proportion of patients with involved surgical margins (R1 rate).
timeFrame: 5 years
measure: Lymph node involvement. This will be measured by the Proportion of patients with involved lymph nodes (N0 vs N1).
timeFrame: 5 years
measure: Survival outcomes measured by Disease Free Survival [DFS])
timeFrame: 5 years
measure: Survival outcomes measured by Local Failure Free Survival [LFFS].
timeFrame: 5 years
measure: Survival outcomes measured by Overall Survival [OS].
timeFrame: 5 years
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Jordan Kharofa, MD
role: PRINCIPAL_INVESTIGATOR
References: