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Adaptive Approach to Neoadjuvant Therapy to Maximize Resection Rates for Pancreatic Adenocarcinoma

Primary Purpose

Pancreas Cancer

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Folfirinox

Gemcitabine

radiation therapy

Pancreatectomy

About this trial

This is an interventional treatment trial for Pancreas Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of ArizonaRecruiting
University of Cincinnati Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant therapy

Arm Description

All patients will receive Neoadjuvant therapy.

Outcomes

Primary Outcome Measures

Measuring the proportion of patients undergoing surgical resection using historical data compared to 32 patients in current study.

Using historical data from prospective trials and meta-analysis of multiple smaller studies, the expected proportion of patients undergoing resection in a mixed population of resectable and borderline resectable cancers is approximately 60%. We ambitiously aim to increase this to 80% or higher. With a one-sided of 0.05 and power of 80%, we will need 32 patients to demonstrate this difference.

Secondary Outcome Measures

Measuring the proportion of patients switching chemotherapy at interim assessment versus those not switching chemotherapy regimen at interim assessment.

Proportions and response rates will be reported with 95% confidence intervals.

Measuring Disease-free survival after resection calculated as time from surgical resection to either disease recurrence or death, whichever comes first.

Disease-free survival after resection will be calculated as time from surgical resection to either disease recurrence or death, whichever comes first.

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.

Measuring the Radiologic response (using RECIST 1.1) to neoadjuvant therapy

Radiologic response using RECIST 1.1

Measuring the Pathologic response to neoadjuvant therapy as Complete Response, Partial Response, Progressive Disease, or Stable Disease.

Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm (<1 cm). Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (0.5 cm). (Note: the appearance of one or more new lesions is also considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Measuring the Proportion of patients undergoing R0 resection, by Calculation of patients undergoing resection versus not able to undergo resection.

Calculation of patients undergoing resection versus not able to undergo resection.

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.

Safety of neoadjuvant therapy will be reported as proportions of patients experiencing toxicities, graded using CTCAE v. 5.0.

Full Information

NCT ID

NCT04594772

First Posted

October 13, 2020

Last Updated

September 14, 2023

Sponsor

University of Cincinnati

1. Study Identification

Unique Protocol Identification Number

NCT04594772

Brief Title

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

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 17, 2021 (Actual)

Primary Completion Date

May 1, 2024 (Anticipated)

Study Completion Date

January 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Cincinnati

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreas Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Neoadjuvant therapy

Arm Type

Experimental

Arm Description

All patients will receive Neoadjuvant therapy.

Intervention Type

Drug

Intervention Name(s)

Folfirinox

Other Intervention Name(s)

5-fluorouracil, irinotecan and oxaliplatin

Intervention Description

Chemotherapy will begin with FOLFIRINOX - a standard regimen used in pancreatic cancer treatment, consisting of 5-fluorouracil (2400 mg/m2), irinotecan (180 mg/m2) and oxaliplatin (85 mg/m2). Treatment will continue for 2 cycles (4 doses), and then re-evaluation will be performed. If a decision to continue with FOLFIRINOX is made, it will be administered for another 4 cycles (8 doses).

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Other Intervention Name(s)

gemcitabine and nab-paclitaxel

Intervention Description

At the first planned analysis, if a switch is indicated based on prespecified criteria , gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) - another standard regimen in this setting - will be used. It will be administered for 4 cycles (12 doses).

Intervention Type

Radiation

Intervention Name(s)

radiation therapy

Intervention Description

Radiation therapy may be used prior to surgery, based on findings on the final pre-operative scan per standard of care. Radiation therapy will be delivered in patients with artery and venous involvement meeting the Intergroup definition for borderline resectable disease. Radiotherapy will be delivered via a hypofractionated approach over 10 fractions and will include target volumes to the primary tumor and elective coverage of vascular structures at risk. Radiation will be delivered with concurrent chemotherapy.

Intervention Type

Procedure

Intervention Name(s)

Pancreatectomy

Intervention Description

Pancreatectomy should occur within 4 to 8 weeks after the last dose of preoperative chemotherapy. Staging laparoscopy may be performed at the time of planned laparotomy but is not required. Either standard or pylorus-preserving pancreaticoduodenectomy, distal subtotal pancreatectomy, or total pancreatectomy may be performed. Surgical drains and enteral tubes (e.g. gastrostomy and/or jejunostomy tubes) may be placed at the discretion of the operating surgeon.

Primary Outcome Measure Information:

Title

Measuring the proportion of patients undergoing surgical resection using historical data compared to 32 patients in current study.

Description

Time Frame

16 months

Secondary Outcome Measure Information:

Title

Measuring the proportion of patients switching chemotherapy at interim assessment versus those not switching chemotherapy regimen at interim assessment.

Description

Proportions and response rates will be reported with 95% confidence intervals.

Time Frame

16 months

Title

Measuring Disease-free survival after resection calculated as time from surgical resection to either disease recurrence or death, whichever comes first.

Description

Disease-free survival after resection will be calculated as time from surgical resection to either disease recurrence or death, whichever comes first.

Time Frame

5 years

Title

Description

Time Frame

5 years

Title

Measuring the Radiologic response (using RECIST 1.1) to neoadjuvant therapy

Description

Radiologic response using RECIST 1.1

Time Frame

5 years

Title

Measuring the Pathologic response to neoadjuvant therapy as Complete Response, Partial Response, Progressive Disease, or Stable Disease.

Description

Time Frame

5 years

Title

Measuring the Proportion of patients undergoing R0 resection, by Calculation of patients undergoing resection versus not able to undergo resection.

Description

Calculation of patients undergoing resection versus not able to undergo resection.

Time Frame

16 months

Title

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.

Description

Safety of neoadjuvant therapy will be reported as proportions of patients experiencing toxicities, graded using CTCAE v. 5.0.

Time Frame

16 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Clinical Trials Office Clinical Trials Office

Phone

513-584-7698

cancer@uchealth.com

First Name & Middle Initial & Last Name or Official Title & Degree

Davendra Sohal, MD

Phone

(513) 475-8500

sohalda@ucmail.uc.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Davendra Sohal, Sohal

Organizational Affiliation

University of Cincinnati

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Arizona

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85724

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Rachna Shroff, MD

Phone

520-694-9057

rshroff@arizona.edu

Facility Name

University of Cincinnati Medical Center

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45219

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christine Vollmer

Phone

513-213-3203

mccordce@ucmail.uc.edu

First Name & Middle Initial & Last Name & Degree

Davendra Sohal, MD

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Adaptive Approach to Neoadjuvant Therapy to Maximize Resection Rates for Pancreatic Adenocarcinoma

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