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

NCT ID: NCT00923299

Last Updated: 2019-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2011-03-31

Brief Summary

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.

Detailed Description

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.

Conditions

Pancreatic Cancer

Study Design

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

Study Groups

cetuximab, trastuzumab

Group Type: OTHER

cetuximab

Intervention Type: DRUG

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.

trastuzumab

Intervention Type: DRUG

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 loading dose of 4 mg/kg as a 90-minute intravenous infusion at J1S1 and then 2 mg/kg as a 30-minute intravenous infusion for all subsequent weekly administrations.

Interventions

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.

Intervention Type: 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 loading dose of 4 mg/kg as a 90-minute intravenous infusion at J1S1 and then 2 mg/kg as a 30-minute intravenous infusion for all subsequent weekly administrations.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

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

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

Sponsors

Institut du Cancer de Montpellier - Val d'Aurelle

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Ychou, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institut du Cancer de Montpellier - Val d'Aurelle

Locations

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 25918250 (View on PubMed)

Other Identifiers

CLCC-THERAPY

Identifier Type: -

Identifier Source: secondary_id

RECF0910

Identifier Type: -

Identifier Source: secondary_id

VA-2008/34

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2008-003988-39

Identifier Type: -

Identifier Source: secondary_id

CDR0000636018

Identifier Type: -

Identifier Source: org_study_id