Clinical trial NCT00923299: Cetuximab and Trastuzumab in Treating Patients With Metastatic Pancreatic Cancer That Progressed After Previous Treatment With Gemcitabine
Official title: Phase I-II Study Evaluating Combined Treatment of Cetuximab and Trastuzumab in Metastatic Pancreatic Cancer Patients Progressing After Gemcitabine Based Chemotherapy.(THERAPY)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Keywords: stage IV pancreatic cancer
recurrent pancreatic cancer
adenocarcinoma of the pancreas
Lead sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
Sponsor class: OTHER
First posted: 2009-06-18
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Recommended dose of trastuzumab when given with cetuximab (Phase I)
timeFrame: 15 days
measure: Objective response rate as assessed by RECIST criteria (Phase II)
timeFrame: Approximately 8 weeks
Secondary outcomes:
measure: Progression-free survival
timeFrame: Approximately 36 months
measure: Overall survival
timeFrame: Approximately 36 months
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
Study officials:
affiliation: Institut du Cancer de Montpellier - Val d'Aurelle
name: Marc Ychou, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.