TORCH: A Study of Tarceva or Chemotherapy for the Treatment of Advanced Non Small Cell Lung Cancer - Full Text View

Sponsor:	National Cancer Institute, Naples
Collaborators:	San Giuseppe Moscati Hospital Princess Margaret Hospital, Canada University of Alberta Second University of Naples
Information provided by:	National Cancer Institute, Naples
ClinicalTrials.gov Identifier:	NCT00349219

Purpose

The purpose of this study is to compare first-line erlotinib followed at progression by second-line chemotherapy vs. first-line chemotherapy followed at progression by second-line erlotinib in the treatment of Advanced Non Small Cell Lung Cancer (NSCLC).

Condition	Intervention	Phase
Advanced Non-Small Cell Lung Cancer	Drug: erlotinib Drug: cisplatin Drug: gemcitabine	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	An International Randomized Phase III Study of First-line Erlotinib Followed by Second-line Cisplatin + Gemcitabine Versus First-line Cisplatin + Gemcitabine Followed by Second-line Erlotinib in Advanced Non Small Cell Lung Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cisplatin Gemcitabine Gemcitabine hydrochloride Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

Further study details as provided by National Cancer Institute, Naples:

Primary Outcome Measures:

overall survival [ Time Frame: one year ] [ Designated as safety issue: No ]
progression free rate of first-line treatment with erlotinib [ Time Frame: after 9 weeks of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

toxicity [ Time Frame: every 3 weeks during treatment, and every 3 months thereafter ] [ Designated as safety issue: Yes ]
progression-free survival [ Time Frame: one year ] [ Designated as safety issue: No ]
quality of life during the first-line therapy [ Time Frame: every 3 weeks during first-line therapy ] [ Designated as safety issue: No ]
prognostic biologic indicators [ Time Frame: end of study ] [ Designated as safety issue: No ]
resource utilization [ Time Frame: every 6 weeks during first-line therapy ] [ Designated as safety issue: No ]
response rate [ Time Frame: at 9 and 18 weeks from treatment initiation ] [ Designated as safety issue: No ]

Estimated Enrollment:	900
Study Start Date:	December 2006
Estimated Study Completion Date:	September 2010
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental erlotinib followed at progression by gemcitabine and cisplatin	Drug: erlotinib erlotinib 150 mg taken orally daily until disease progression Drug: cisplatin cisplatin 80 mg/m2 IV day 1 every 3 weeks given in second-line therapy Drug: gemcitabine gemcitabine 1200 mg/m2 IV days 1 and 8 every 3 weeks, given in second-line
2: Active Comparator cisplatin and gemcitabine chemotherapy for 6 cycles, followed at progression by erlotinib	Drug: cisplatin cisplatin 80 mg/m2 IV day 1 every 3 weeks for 6 cycles Drug: gemcitabine gemcitabine 1200 mg/m2 IV days 1 and 8 every 3 weeks for 6 cycles Drug: erlotinib erlotinib 150 mg orally taken daily as second line therapy (after disease progression on chemotherapy)

Detailed Description:

Chemotherapy for patients affected by advanced NSCLC has demonstrated only modest improvement in survival rates over best supportive care: the prognosis of patients remains poor and the side effects are considerable. Therefore, novel agents are urgently needed for this disease. One way to improve effectiveness of therapies is to use non-chemotherapeutic agents that act on biological targets and cause fewer systemic side effects. Erlotinib(Tarceva)is a biological therapy that in recent clinical trials has shown promise in first- and second-line treatment of advanced NSCLC.

In this trial, patients will be randomized to one of two treatment strategies:

- erlotinib taken by mouth daily; and, if disease progression occurs, to be followed by chemotherapy with cisplatin and gemcitabine at standard doses for 6 cycles

OR

- chemotherapy with cisplatin and gemcitabine given intravenously at standard doses for 6 cycles; and if disease progression occurs to be followed by erlotinib taken by mouth daily

The study is conducted with the partial support of Roche, S.p.A.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of cytologically or histologically confirmed non-small cell lung cancer
Metastatic (stage IV) or locally advanced (stage IIIB, with metastasis to supraclavicular nodes or with pleural effusion).
Both patients at first diagnosis or those with disease recurrence after former surgery are eligible.
At least one target or non-target lesion according to RECIST criteria
Male or female > 18 years of age (Italy upper age limit 70 years)
ECOG PS 0 or 1
Life expectancy of > 3 months
Neutrophils > 1,500 mm3, platelets > 100,000 mm3, and hemoglobin > 9 g/dL
Bilirubin level either normal or < 1.5 x ULN
AST (SGOT) and ALT (SGPT) < 2.5 x ULN (< 5 x ULN if liver metastasis are present)
Serum creatinine < 1.5 x ULN
Effective contraception for both, male and female patients if the risk of conception exists
Signed written informed consent

Exclusion Criteria:

Prior exposure to agents directed at the HER axis (e.g. gefitinib, cetuximab, trastuzumab).
Prior chemotherapy or therapy with systemic anti-neoplastic therapy (e.g., monoclonal antibody therapy) for advanced disease. Prior surgery and/or localised irradiation is permitted. Prior neoadjuvant chemotherapy for operable disease or adjuvant chemotherapy is permitted if it did not contain gemcitabine and if at least 1 year elapsed from the end of chemotherapy and the date of relapse.
Any unstable systemic disease (including active infections, significant cardiovascular disease or myocardial infarction within the previous year, any significant hepatic, renal or metabolic disease), metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of study medications or render the patient at high risk from treatment complications.
Any other malignancies within past 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically resected prostate cancer with normal PSA).
Patients are excluded if they have brain metastasis or spinal cord compression that has not yet been definitively treated with surgery and/or radiation; previously diagnosed and treated CNS metastases or spinal cord compression without evidence of stable disease (clinically stable imaging) for at least 2 months will also cause patients to be excluded. Patients with asymptomatic CNS metastases and not requiring steroids to control symptoms can be included, even if on anti-seizure medications.
HIV positive patients
Any inflammatory changes of the surface of the eye at baseline
Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease.
Nursing and/or pregnant females
Known or suspected hypersensitivity to any of the study drugs.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00349219

Show 84 Study Locations

Sponsors and Collaborators

National Cancer Institute, Naples

San Giuseppe Moscati Hospital

Princess Margaret Hospital, Canada

University of Alberta

Second University of Naples

Investigators

Principal Investigator:	Cesare Gridelli, M.D.	S.G. Moscati Hospital, Avellino, Italy
Principal Investigator:	Charles Butts, M.D.	University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
Principal Investigator:	Fortunato Ciardiello, M.D., Ph.D.	Second University of Naples, Italy; Chair Medical Oncology
Principal Investigator:	Ronald Feld, M.D.	Princess Margaret Hospital, Divison of Medical Oncology, Toronto, Ontario, Canada
Principal Investigator:	Ciro Gallo, M.D., Ph.D.	Second University of Naples, Italy; Chair Medical Statistics
Principal Investigator:	Francesco Perrone, M.D., Ph.D.	National Cancer Institute, Naples, Italy; Director Clinical Trials Unit

More Information

No publications provided

Responsible Party:	National Cancer Institute, Naples ( Francesco Perrone, Director Clinical Trials Unit )
Study ID Numbers:	TORCH, EUDRACT number: 2005-005968-90
Study First Received:	July 4, 2006
Last Updated:	November 19, 2009
ClinicalTrials.gov Identifier:	NCT00349219 History of Changes
Health Authority:	Italy: Ethics Committee

Keywords provided by National Cancer Institute, Naples:

first-line
second-line
targeted therapy

Additional relevant MeSH terms:

Thoracic Neoplasms
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Protein Kinase Inhibitors
Neoplasms by Site
Cisplatin
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses

Gemcitabine
Erlotinib
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Enzyme Inhibitors
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Carcinoma
Neoplasms
Radiation-Sensitizing Agents
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on February 08, 2010