Cetuximab And Trastuzumab In Treating Patients With Metastatic Pancreatic Cancer That Progressed After Previous Treatment With Gemcitabine

Study Overview

Cetuximab and Trastuzumab in Treating Patients With Metastatic Pancreatic Cancer That Progressed After Previous Treatment With Gemcitabine

RATIONALE: Monoclonal antibodies, such as cetuximab and trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving cetuximab together with trastuzumab may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of trastuzumab when given together with cetuximab and to see how well it works in treating patients with metastatic pancreatic cancer that progressed after previous treatment with gemcitabine.

OBJECTIVES: Primary * Determine the recommended dose of trastuzumab when given with cetuximab in patients with metastatic pancreatic cancer that progressed after gemcitabine-based chemotherapy. (Phase I) * Evaluate the objective response rate as assessed by RECIST criteria. (Phase II) Secondary * Evaluate the safety profile as assessed by NCI CTCAE v3.0. * Evaluate progression-free survival. * Evaluate overall survival. OUTLINE: This is a multicenter, phase I dose-escalation study of trastuzumab followed by a phase II study. Patients receive cetuximab IV over 1-2 hours and trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.

Pancreatic Cancer

DRUG: cetuximab
DRUG: trastuzumab

CDR0000636018
CLCC-THERAPY
RECF0910
VA-2008/34
EUDRACT-2008-003988-39

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2009-06-17	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2019-04-12
First Submitted that Met QC Criteria 2009-06-17	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2019-04-16
First Posted (ACTUAL) 2009-06-18	Results First Posted N/A	Last Verified 2017-08

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
OTHER: cetuximab, trastuzumab	DRUG: cetuximab Cetuximab at the initial dose of 400 mg/m² (J1S1) as a 2-hour infusion and then at the 250 mg/m² dose as a 1-hour infusion in subsequent weeks. DRUG: trastuzumab Two dose levels of trastuzumab will be evaluated for Phase 1: * Level 1: a loading dose of 3 mg/kg as a 90-minute intravenous infusion at J1S1 and then 1.5 mg/kg as a 30-minute intravenous infusion for all subsequent weekly administrations; * Level 2: a

Participant Group/Arm

Intervention/Treatment

OTHER: cetuximab, trastuzumab

DRUG: cetuximab

Cetuximab at the initial dose of 400 mg/m² (J1S1) as a 2-hour infusion and then at the 250 mg/m² dose as a 1-hour infusion in subsequent weeks.

DRUG: trastuzumab

Two dose levels of trastuzumab will be evaluated for Phase 1: * Level 1: a loading dose of 3 mg/kg as a 90-minute intravenous infusion at J1S1 and then 1.5 mg/kg as a 30-minute intravenous infusion for all subsequent weekly administrations; * Level 2: a

Primary Outcome Measures	Measure Description	Time Frame
Recommended dose of trastuzumab when given with cetuximab (Phase I)	From baseline to the end of treatment	15 days
Objective response rate as assessed by RECIST criteria (Phase II)	From baseline to the end of treatment	Approximately 8 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Progression-free survival	From baseline to the end of study	Approximately 36 months
Overall survival	From baseline to the end of study	Approximately 36 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically confirmed metastatic adenocarcinoma of the pancreas

Progressed after first-line or adjuvant gemcitabine-based chemotherapy
Measurable disease as assessed by RECIST criteria
No known brain metastasis or symptomatic carcinomatous leptomeningitis

WHO performance status 0-1
Life expectancy ≥ 3 months
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 9 g/dL
Creatinine ≤ 1.5 times upper limit of normal (ULN)
Total bilirubin ≤ 2.5 times ULN
ALT/AST ≤ 5 times ULN
LVEF ≥ 55%
Not pregnant or nursing
Fertile patients must use effective contraception
No significant comorbidities, including any of the following:

Cardiovascular disease
Documented history of congestive heart failure
Uncontrolled, high-risk arrhythmia
Angina pectoris requiring treatment
Clinically significant valvular disease
Evidence of transmural myocardial infarction by ECG
Uncontrolled hypertension
Active bleeding
Clinically significant active infection
Severe dyspnea at rest
Oxygen-dependency
No other malignancy except basal cell carcinoma of the skin
No severe hypersensitivity to cetuximab or trastuzumab
No medical or psychological condition that would preclude study completion or giving informed consent
No legal incapacity or limited legal capacity

See Disease Characteristics
No prior cetuximab or trastuzumab
No other concurrent experimental drugs or anticancer therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Marc Ychou, MD, PhD, Institut du Cancer de Montpellier - Val d'Aurelle

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Assenat E, Azria D, Mollevi C, Guimbaud R, Tubiana-Mathieu N, Smith D, Delord JP, Samalin E, Portales F, Larbouret C, Robert B, Bibeau F, Bleuse JP, Crapez E, Ychou M, Pelegrin A. Dual targeting of HER1/EGFR and HER2 with cetuximab and trastuzumab in patients with metastatic pancreatic cancer after gemcitabine failure: results of the "THERAPY"phase 1-2 trial. Oncotarget. 2015 May 20;6(14):12796-808. doi: 10.18632/oncotarget.3473.

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Clinical Trial Record