Chemotherapy Selection Based on Therapeutic Targets for Advanced Pancreatic Cancer

Phase II Study of Chemotherapy Selection Based on Therapeutic Targets for the Treatment of Advanced Pancreatic Cancer

In recent years, treatment of advanced pancreatic cancer is changing. Currently, there are several active schedules of chemotherapy that can be used, such as gemcitabine as monotherapy or in combination with capecitabine or erlotinib, and FOLFIRINOX. Moreover, the development of biomarker (therapeutic targets) that can predicte response to treatment is a new important tool to be used in clinical practice to select the best scheme for each patient. Preliminary studies showed that therapeutic target determination, using tumor tissue collected from patients, could determine the presence of groups of "chemotherapy responders". Such is the case of EGFR amplification and/or K-Ras gene status and correlation with response to erlotinib. Moreover, Thymidilate Synthase, Thimidine Phosphorylase, ERCC-1 and Topoisomerase I expression by immunohistochemistry in GI tumor samples has been related to resistance or response to 5FU-capecitabine, oxaliplatin and irinotecan respectively. Based on this data the investigators designed a phase II clinical trial to evaluate the efficacy of selected treatment for pancreatic cancer patients based on the determination of therapeutic targets. The therapeutic target-driven treatment efficacy will be compared to the prospective treatment of a control group of patients treated at the discretion of the physician-researcher

Study Overview

• Status: Unknown
• Conditions: Carcinoma, Pancreatic Ductal
• Intervention / Treatment: Drug: Targeted Therapy Tailored Treatment; Drug: Standard Chemotherapy

Detailed Description

Study Phase: Phase 2 Trial

Study Objetives:

• Primary end-point. Proportion of patients alive after 12 months in patients with advanced pancreatic carcinoma individually selected and grouped according to the expression in tumor tissue for therapeutic targets.
• Secondary end-points. 1. Assessing the feasibility of the method of patient-treatment-selection based on tumor tissue expression of therapeutic targets. 2. Overal survival comparison between Gemcitabine single agent treatment and the rest of chemotherapy schedules. 3. Determination of progression-free survival for each treatment group. 4. Determination of toxicity in all the patients.

Study population and Number of subject: A total of 60 pancreatic cancer patients with advanced pancreas cancer with no previous systemic treatment are expected to be enrolled.

Study design and schedule. Patients will be randomized (1:1) to a control arm or an experimental treatment arm guided by therapeutic targets. In the control arm, patients are treated with conventional chemotherapy regimens at the discretion of the investigator. In the experimental arm, patients are treated as determined in tumor tissue available for biomarker TS, TP, ERCC-1, Topo-1, K-Ras mutation and EGFR FISH, choosing FOLFIRINOX schemas, FOLFOX, FOLFIRI, Gemcitabine-Capecitabine Gemcitabine-Erlotinib, Gemcitabine single agent. All patients will be analyzed by intention to treat

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28050
    • Recruiting
    • Centro Integral Oncológico Clara Campal
    • Contact: Manuel Hidalgo, MD, PhD; Email: mhidalgo@cnio.es
    • Sub-Investigator: Jesus Rodriguez-Pascual
    • Sub-Investigator: Antonio Cubillo
    • Sub-Investigator: Pia Morelli
    • Sub-Investigator: Elena Garcia
    • Sub-Investigator: Barbara Angulo
    • Sub-Investigator: Ulpiano Lopez de la Guardia
    • Sub-Investigator: Emilio de Vicente
    • Sub-Investigator: Eduardo Garcia-Rico
    • Sub-Investigator: Ignacio Juez
    • Sub-Investigator: Ana Ruiz

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologic diagnosis of pancreas adenocarcinoma
• Clinical stage IV
• Feasible patient for chemotherapy
• Availability of tumor tissue or possibility of a tumor biopsy to define therapeutic targets
• Informed written consent

Exclusion Criteria:

• Previous systemic treatment for advanced pancreas adenocarcinoma
• Contraindication to the administration of any of the drugs used in the study: capecitabine, 5Fluouracil, irinotecan, oxaliplatin, gemcitabine or erlotinib

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tarteted Therapy	Drug: Targeted Therapy Tailored Treatment; Targeted therapy tailored treatment, based on molecular determination in pancreas cancer specimen; Tim Synthase (TS) (neg), ERCC-1 (neg), Topoisomerase I (Topo I) (pos) : FOLFIRINOX; TS (neg), ERCC-1 (neg), Topo I (neg): FOLFOX; TS (neg), ERCC-1 (pos), Topo I (pos): FOLFIRI; TS (neg), ERCC-1 (pos), Topo I (neg): Capecitabine/Gemcitabine; TS (pos), EGFR Not Amplificate, K-Ras Mutation (pos) : Gemcitabine single agent; TS (pos), EGFR Ampl or K-Ras mut (neg): Gemcitabine plus Erlotinib; Other Names: Individualized treatment selection based on predictors of response biomarkers
Active Comparator: Standard Chemotherapy	Drug: Standard Chemotherapy; Patients treated based on investigator´s criteria: : FOLFIRINOX, FOLFOX, FOLFIRI, Capecitabine-Gemcitabine, Erlotinib-Gemcitabine or Gemcitabine single agent; Other Names: Treatment at the investigator's discretion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	1 year

Collaborators and Investigators

• Sponsor: Sofia Perea, Director Clinical Trials Unit.
• Investigators: Principal Investigator: Manuel Hidalgo, MD

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: July 5, 2011
• First Submitted That Met QC Criteria: July 13, 2011
• First Posted (Estimate): July 14, 2011

Study Record Updates

• Last Update Posted (Estimate): March 27, 2012
• Last Update Submitted That Met QC Criteria: March 24, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Pancreas cancer; Targeted Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Carcinoma, Ductal; Carcinoma, Pancreatic Ductal
• Other Study ID Numbers: TARGTHPANC 001; 2011-001017-13 (EudraCT Number)