Clinical trial NCT04594772: Adaptive Approach to Neoadjuvant Therapy to Maximize Resection Rates for Pancreatic Adenocarcinoma
Official title: An Adaptive Approach to Neoadjuvant Therapy to Maximize Resection Rates for Pancreatic Adenocarcinoma: A Phase II Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pancreas Cancer
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
First posted: 2020-10-20
Enrollment: 32
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: The purpose of this study is to determine if neoadjuvant therapy to increases resection rate for pancreatic adenocarcinoma.

Detailed description: There are no investigational agents being used in this trial, and all doses, schedules, and modifications are based on established standards of care. The research components of this study will be the use of the two evaluation timepoints for assessment of efficacy of pre-resection chemotherapy (including the evaluation criteria defined within this protocol), and the collection of correlative blood and tissue samples.

Chemotherapy will begin with FOLFIRINOX - a standard regimen used in pancreatic cancer treatment, consisting of 5-fluorouracil, irinotecan and oxaliplatin. At the first planned analysis, if a switch is indicated based on prespecified criteria (see Section 8.2 for the specific adaptive decision criteria), gemcitabine and nab-paclitaxel - another standard regimen in this setting - will be used. Radiation therapy may be used prior to surgery, based on findings on the final pre-operative scan per standard of care.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of pancreatic carcinoma or adenocarcinoma confirmed by tissue. Histologies other than carcinoma or adenocarcinoma are not allowed.
* Resectable or borderline resectable primary tumor, evaluated on a baseline contrast-enhanced CT or MRI scan (CT Chest/Abdomen/Pelvis with contrast is preferred; if MRI used at baseline, then follow up with MRI as well), and defined using Intergroup criteria:

  * Tumor vessel wall interface 0-360 for portal and superior mesenteric veins.
  * Tumor vessel wall interface \<180 for celiac, common hepatic, and superior mesenteric arteries.
  * No suspicious metastatic lesions (no visceral lesions, no enlarged nodes outside the surgical basin).
* Age ≥18 years.
* ECOG performance status ≤ 1.
* No prior therapy for index pancreatic cancer.
* Patients must have adequate organ and marrow function as defined in protocol
* Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are 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 history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Patients with a prior malignancy (with all treatment completed at least 2 years prior to enrollment) whose natural history does not have the potential to interfere with the safety or efficacy assessment of this study are eligible.
* Women of child-bearing potential and fertile men must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of active treatment.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Patients with uncontrolled intercurrent illness or comorbidities that would, in the opinion of the treating physician, prevent receipt of standard of care chemotherapy, radiation or surgery.
* Pregnant women or women who are breastfeeding are excluded from this study.
* Patients who are currently receiving any other investigational agents. Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI.
* Patients with psychiatric illness/social situations that would limit compliance with study requirements, per the PI's discretion.
* Patients who, in the opinion of the PI, will be unable to adhere to study requirements.

Primary outcomes:
measure: Measuring the proportion of patients undergoing surgical resection using historical data compared to 32 patients in current study.
timeFrame: 16 months
Secondary outcomes:
measure: Measuring the proportion of patients switching chemotherapy at interim assessment versus those not switching chemotherapy regimen at interim assessment.
timeFrame: 16 months
measure: Measuring Disease-free survival after resection calculated as time from surgical resection to either disease recurrence or death, whichever comes first.
timeFrame: 5 years
measure: Overall survival will be calculated as time from registration on study to death. For survival time calculation, the Kaplan-Meier method will be used, and if the endpoint is not reached, the cases will be censored.
timeFrame: 5 years
measure: Measuring the Radiologic response (using RECIST 1.1) to neoadjuvant therapy
timeFrame: 5 years
measure: Measuring the Pathologic response to neoadjuvant therapy as Complete Response, Partial Response, Progressive Disease, or Stable Disease.
timeFrame: 5 years
measure: Measuring the Proportion of patients undergoing R0 resection, by Calculation of patients undergoing resection versus not able to undergo resection.
timeFrame: 16 months
measure: Measuring the safety of neoadjuvant therapy will be determined using CTCAE v5, reported as proportions of patients experiencing toxicities, graded using CTCAE v. 5.0.
timeFrame: 16 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Davendra Sohal, Sohal
role: PRINCIPAL_INVESTIGATOR
References: