Chemotherapy Selection Based on Therapeutic Targets for Advanced Pancreatic Cancer

NCT ID: NCT01394120

Last Updated: 2012-03-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2013-12-31

Brief Summary

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

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

Conditions

Carcinoma, Pancreatic Ductal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tarteted Therapy

Group Type: EXPERIMENTAL

Targeted Therapy Tailored Treatment

Intervention Type: DRUG

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

Standard Chemotherapy

Group Type: ACTIVE_COMPARATOR

Standard Chemotherapy

Intervention Type: DRUG

Patients treated based on investigator´s criteria: : FOLFIRINOX, FOLFOX, FOLFIRI, Capecitabine-Gemcitabine, Erlotinib-Gemcitabine or Gemcitabine single agent

Interventions

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

Intervention Type: DRUG

Standard Chemotherapy

Patients treated based on investigator´s criteria: : FOLFIRINOX, FOLFOX, FOLFIRI, Capecitabine-Gemcitabine, Erlotinib-Gemcitabine or Gemcitabine single agent

Intervention Type: DRUG

Other Intervention Names

Individualized treatment selection based on predictors of response biomarkers; Treatment at the investigator's discretion

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sofia Perea, Director Clinical Trials Unit.

OTHER

Sponsor Role: lead

Responsible Party

Sofia Perea, Director Clinical Trials Unit.

Director Clinical Trial Unit

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Manuel Hidalgo, MD

Role: PRINCIPAL_INVESTIGATOR

Locations

Centro Integral Oncologico Clara Campal

Madrid, , Spain

Site Status: RECRUITING

Countries

Spain

Facility Contacts

Manuel Hidalgo, MD, PhD

Role: primary

mhidalgo@cnio.es

Other Identifiers

2011-001017-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TARGTHPANC 001

Identifier Type: -

Identifier Source: org_study_id