Patient Derived Cancer Cell Lines in Identifying Molecular Changes in Patients With Previously Untreated Pancreatic Cancer Receiving Gemcitabine Hydrochloride-Based Chemotherapy

Generation of Patient Derived Pancreatic Cancer Cell Lines to Determine Mechanisms of Chemoresistance

This pilot research trial studies patient derived cancer cell lines in identifying molecular changes in patients with previously untreated pancreatic cancer and are receiving gemcitabine hydrochloride-based chemotherapy. Cell lines refer to samples taken from the patient's tumor to grow for many months or years in a laboratory, and can therefore be studied scientifically. Studying cell lines in the laboratory may help doctors understand the genetic changes that occur to the tumor during chemotherapy that allows the tumor to resist or grow despite treatment.

Study Overview

• Status: Withdrawn
• Conditions: Pancreatic Ductal Adenocarcinoma; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Cytology Specimen Collection Procedure

Detailed Description

PRIMARY OBJECTIVES:

I. Compare the genetic profile of the tumor after progression has occurred, to the tumor prior to treatment.

SECONDARY OBJECTIVES:

I. Additional molecular patterns, beyond genetics, will be analyzed, including ribonucleic acid (RNA) and protein expression.

OUTLINE:

Tissue and blood samples are collected for genetic analysis via sequencing from patients receiving gemcitabine hydrochloride intravenously or gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation. Chemotherapy is not part of the protocol. Per standard of care, patients receive gemcitabine hydrochloride (IV) the first 3 of 4 weeks (qw 3/4 wk) or gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation IV qw 3/4 wk in the absence of disease progression or recurrence.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with treatment naive pancreatic ductal adenocarcinoma (PDA) treated at Thomas Jefferson University or Georgetown University

Description

Inclusion Criteria:

1. Suspected or confirmed pancreatic adenocarcinoma, any stage
2. >18 years of age
3. No prior systemic chemotherapy for pancreatic cancer, or currently undergoing first-line treatment for pancreatic cancer, or completed only first-line treatment for pancreatic cancer
4. A plan to undergo gemcitabine-based chemotherapy at Thomas Jefferson or a collaborating institution
5. Abdominal/pelvic CT scan or MRI within 4 months of the study
6. Signed study-specific informed consent

Exclusion Criteria:

1. Pregnancy
2. Prior systemic chemotherapy for pancreatic cancer
3. Gender/Minority/Pediatric Inclusion for Research

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patient derived cancer cell lines; Patients receive gemcitabine hydrochloride IV qw 3/4 wk or gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation IV qw 3/4 wk in the absence of disease progression or recurrence per standard of care. Tissue and blood samples are collected for genetic analysis via sequencing.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Cytology Specimen Collection Procedure; Correlative studies; Other Names: Cytologic Sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genomic profiles of post-treatment samples with acquired resistance against pre-treatment and germline controls	This method includes a preprocessing step to filter out unreliable reads, a statistical classification step to identify point mutations that differ from both the reference genome hg19 and the control sample at controlled false-positive rate, and a post-processing step to eliminate platform-specific artifacts inherent in next generation sequencing. ANNOVAR software will then be used to analyze candidate point mutations for their predicted impact on protein function, which will be used to select and prioritize specific mutations for validation and/or further study.	Up to 5 years
Identification of germline mutations in known cancer genes from whole blood genomic deoxyribonucleic acid, and somatic mutations in conditionally reprogrammed cells derived from pre-treatment and post-treatment (e.g., resistant) tumors	The study will be considered a positive study if in any of the patients' samples, unique mutations are identified in the post-treatment derived cell lines that are not present in the pre-treatment derived cell lines from the same patient.	Up to 5 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Collaborators: Celgene
• Investigators: Principal Investigator: Jordan Winter, MD, Thomas Jefferson University

Publications and helpful links

Helpful Links

• Sidney Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Jefferson University Hospitals

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2013
• Primary Completion (Actual): December 15, 2016
• Study Completion (Actual): December 15, 2016

Study Registration Dates

• First Submitted: March 19, 2015
• First Submitted That Met QC Criteria: April 7, 2015
• First Posted (Estimate): April 10, 2015

Study Record Updates

• Last Update Posted (Actual): September 8, 2017
• Last Update Submitted That Met QC Criteria: September 5, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: 13C.628; 2013-077 (CCRRC)