Immune Response on Neoadjuvant Therapy in Non-small-cell Lung Cancer (NSCLC)

This study has been completed.
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Sanofi
TAKO - Tiroler Arbeitskreis Onkologie
Information provided by (Responsible Party):
Wolfgang Hilbe, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00406302
First received: December 1, 2006
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

Primary objective is to assess the overall response rate (ORR) after induction therapy with docetaxel in combination with CDDP and cetuximab in patients with NSCLC stage IB, II, and IIIa. ORR will be determined by the percentage of patients achieving objective response rates (CR + PR) according to the RECIST guidelines.


Condition Intervention Phase
Carcinoma, Non-small-cell Lung
Drug: Docetaxel
Drug: oxaliplatin
Drug: cetuximab
Procedure: surgery
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter Phase II Study Evaluating Docetaxel, CDDP, and Cetuximab as Induction Regimen Prior to Surgery in Chemo-naive Patients With NSCLC Stage IB, II and IIIA

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • overall response rate (complete plus partial response) according to RECIST guidelines [ Time Frame: June 2011 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pathological response [ Time Frame: June 2011 ] [ Designated as safety issue: No ]
  • Metabolic response [ Time Frame: June 2011 ] [ Designated as safety issue: No ]
  • Immunological response [ Time Frame: June 2011 ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: June 2011 ] [ Designated as safety issue: No ]
  • Safety profile and tolerability [ Time Frame: June 2011 ] [ Designated as safety issue: Yes ]
  • overall response rate (complete plus partial response) according to RECIST guidelines [ Time Frame: June 2011 ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: January 2007
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Docetaxel
    75mg/m², day 1,22
    Other Name: Taxotere
    Drug: oxaliplatin
    40mg/m², d1,2,22,23
    Other Name: CDDP
    Drug: cetuximab
    400mg/m² (day1), 250mg/m² (day 8,15,22,29,36)
    Other Name: Erbitux
    Procedure: surgery
    28 days after end of induction chemotherapy
Detailed Description:

Primary objective is to assess the overall response rate (ORR) after induction therapy with docetaxel in combination with CDDP and cetuximab in patients with NSCLC stage IB, II, and IIIa. ORR will be determined by the percentage of patients achieving objective response rates (CR + PR) according to the RECIST guidelines.

Secondary objective is

  • To evaluate pathological response determined by histological work up of the surgical specimens according to TNM stages.
  • To evaluate the metabolic response determined by PET analysis.
  • To assess overall survival (OS) (median survival time and percentage of 1-year survival). OS is defined as time elapsed from the date of patient inclusion until recorded date of death.
  • To characterize and quantify toxic effects of the scheduled therapy. Safety profile and tolerability will be assessed by recording adverse events, clinically significant laboratory abnormalities, physical examination and vital signs. Toxicities will be evaluated according to the NCI-CTC Toxicity Criteria and adverse events which are not reported in NCI-CTC will be graded as mild, moderate, severe or life-threatening. All patients who received any of the scheduled therapy will be included in the overall toxicity analysis.
  • To evaluate the immunological response determined by regulatory T-cells and immune activation markers, to define chemoresistance by pharmacogenomic testing.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Histology and staging of the disease

  • Histological confirmed NSCLC; histology may include: large cell, squamous cell or adenocarcinoma but no SCLC.
  • Anatomically and functionally resectable NSCLC stage IB (T2N0) stage II (T1-2 N1, T3 N0) or stage IIIA (T3 N1) (see TAKO guidelines 2006, www.tako.or.at)
  • Measurable disease according to RECIST criteria

General conditions

  • 18-80 years.
  • WHO 0-2; life expectancy of more than 3 months
  • Effective contraception for both male and female patients if the risk of conception exists
  • Adequate respiratory function, sufficient for necessary surgical treatment
  • Adequate hematological function (Hb > 10 g/dl, ANC > 2.0 x 10 9/L, platelets > 100 x 10 9/L).
  • Adequate renal and hepatic functions: total bilirubin within normal limits, serum creatinine within normal limits, in case of limit value the creatinine clearance should be > 60 ml/min, ASAT and ALAT < 2.5 x UNL, alkaline phosphatase < 5 x UNL.

Initial work-up

  • Complete initial work-up within three weeks prior to first infusion includes chest CT scan, abdominal CT-scan, brain CT scan if indicated, PET-scan, bronchoscopy and mediastinoscopy, pulmonary function. Within 7 days prior to inclusion laboratory investigations and biological work up.
  • Signed initial consent prior to protocol specific procedures.

Exclusion Criteria:

Diagnosis

  • Evidence of brain metastases or other distant metastasis equivalent to stage IV disease
  • History of prior malignancies, except for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix or other curatively treated cancer with no evidence of disease for at least five years
  • Other serious concomitant illness or medical condition:
  • Congestive heart failure or angina pectoris, except if medically controlled, history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or arrhythmia
  • History of significant neurological or psychiatric disorders, including dementia or seizure
  • Active infection requiring i.v. antibiotics
  • Active ulcer, unstable diabetes mellitus or other contraindications to corticotherapy
  • Current peripheral neuropathy WHO grade > 2

Prior or concurrent therapy

  • Prior chemotherapy or immunotherapy for NSCLC
  • Prior surgery or radiotherapy for NSCLC
  • Concurrent treatment with other experimental drugs, unapproved medical procedures or other anticancer therapy
  • Concurrent continuous treatment with systemic steroids for antiemetic use, intermittent application is allowed

General conditions

  • Pregnant (absence to be confirmed by ß-HCG-test) or lactating patients
  • Patients (M/F) with reproductive potential not implementing adequate contraceptive measurements
  • Participation in other clinical trials with experimental agents or non approved medical procedures during study and within 30 days prior to study entry
  • Psychological, familial, sociological or geographical conditions which do not permit medical follow-up and compliance with the study protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00406302

Locations
Austria
University Hospital, Internal Medicine
Innsbruck, Tirol, Austria, A-6020
Hosptial Kufstein
Kufstein, Tirol, Austria, A-6330
Hospital Natters
Natters, Tirol, Austria, A-6161
Hospital Zams
Zams, Tirol, Austria, A-6511
Prim. Dr. Bolitschek
Linz, Austria, A-4010
Prim. Dr. H. Schinko
Linz, Austria, A-4020
OA Dr. Rainer Kolb
Wels, Austria, A-4600
Sponsors and Collaborators
Wolfgang Hilbe
Merck Sharp & Dohme Corp.
Sanofi
TAKO - Tiroler Arbeitskreis Onkologie
Investigators
Principal Investigator: Wolfgang Hilbe, Prof. Dr. University Hospital Innsbruck, Internal Medicine
  More Information

Publications:
Responsible Party: Wolfgang Hilbe, Ao. Univ. Prof. Dr., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT00406302     History of Changes
Other Study ID Numbers: 2006-004639-31
Study First Received: December 1, 2006
Last Updated: April 28, 2014
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Vienna:
NSCLC
non-small-cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Cetuximab
Docetaxel
Antimitotic Agents
Antineoplastic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 21, 2014