Docetaxel/Pemetrexed as 1st Line Treatment in Patients With Non Small Cell Lung Cancer (NSCLC)

Study Description

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Brief Summary:

This trial will determine the maximum tolerated dose the recommended phase II dose and the efficacy of this combination in locally advanced or metastatic NSCLC patients

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer	Drug: Docetaxel; Drug: Pemetrexed	Phase 1; Phase 2

Detailed Description:

Docetaxel as single-agent therapy (100 mg/m2 and 75 mg/m2, every 3 weeks) produces response rates of 26% to 54%. Docetaxel has proven superior compared to best supportive care (BSC) in chemotherapy-naïve as well as in platinum pretreated patients. In addition, docetaxel is active in cisplatin refractory or resistant patients, producing responses ranging from 18% to 25%, implying a lack of cross-resistance between docetaxel and cisplatin, probably due to their different mechanisms of action. Furthermore, docetaxel is associated with significant prolongation of survival when administered as second line therapy, in pretreated patients with advanced NSCLC. Phase II studies of pemetrexed in previously untreated patients with NSCLC have demonstrated single agent response rates of 17% to 23%. A phase II study of pemetrexed in patients with advanced NSCLC, who had progressed during or within 3 months of completing first-line chemotherapy, demonstrated a response rate of 8.9% and median survival time of 5.7 months. Multivariate analysis established an association between an increased risk of severe pemetrexed toxicity and elevated homocysteine (folate and/or B12 vitamin deficiency marker) levels. Since December 1999, all pemetrexed-treated patients are required to receive folic acid and Vitamin B12. A recently reported phase III study compared pemetrexed with docetaxel as 2nd line therapy in patients with advanced NSCLC. Treatment with pemetrexed resulted in clinically equivalent efficacy outcomes, but with significantly fewer side effects compared with docetaxel.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	70 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase I/II Study Of The Docetaxel/Pemetrexed Combination As First Line Treatment In Patients With Advanced/Metastatic NSCLC
Study Start Date :	May 2006
Actual Primary Completion Date :	May 2009
Actual Study Completion Date :	May 2009

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 1	Drug: Docetaxel; Docetaxel at starting dose of 65 mg/m2 IV on day 1 every 3 weeks for a total of 6 cycles; Other Name: Taxotere Drug: Pemetrexed; Pemetrexed at starting dose of 400 mg/m2 IV on day 1 every 3 weeks for a total of 6 cycles; Other Name: Alimta

Outcome Measures

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Primary Outcome Measures :

1. Evaluation of Dose Limited Toxicity and Maximum Tolerated Dose for the docetaxel/pemetrexed doublet [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. Response rate for the docetaxel/pemetrexed doublet [ Time Frame: 2 years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Histologically confirmed inoperable (stage IIIB-IV) NSCLC. A block of Formaline Fixed Parafine Embedded tissue representative for the primary diagnosis should be available for genomic analysis (phase II part)
• Written informed consent
• Prior chemotherapy with platinum compounds in association with or without taxanes (phase I part)
• Previously untreated with docetaxel and pemetrexed (phase II part)
• Bidimensionally, non-irradiated measurable disease (according to RECIST criteria) (phase II)
• Age ≥18 years
• World Health Organization (WHO) performance status (PS) 0-2
• Life expectancy of at least 12 weeks
• Serum bilirubin less than 1.5 times the upper normal limit (UNL)
• AST and ALT less than 2.5 times the UNL in the absence of demonstrable liver metastases, or less than 5 times the UNL in the presence of liver metastases.
• Serum creatinine less than 1.5 times the UNL
• Neutrophil count more than 1.5x 109 /L
• Platelet count more than 100x 109 /L

Exclusion Criteria:

• Other co-existing malignancies or malignancies diagnosed within the last 5 years (with the exception of basal cell carcinoma or cervical cancer in situ)
• Any evidence of severe uncontrolled concomitant disease (in the opinion of the investigator)
• Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy
• Patients with unstable central nervous system metastases
• Malnutrition (loss of ≥ 20% of the original body weight)
• Performance status: 4
• Psychiatric illness or social situation that would preclude study compliance
• Pregnant or lactating women

Contacts and Locations

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Locations

Greece
University General Hospital of Alexandroupolis, Dep of Medical Oncology
Alexandroupolis, Greece
"IASO" General Hospital of Athnes, Dep of Medical Oncology
Athens, Greece
"Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine
Athens, Greece
Air Forces Military Hospital, Dep of Medical Oncology
Athens, Greece
Sismanogleio General Hospital, 1st, 2nd Dep of Pulmonary Diseases
Athens, Greece
Sotiria" General Hospital, 1st Dep of Pulmonary Diseases
Athens, Greece
"Diabalkaniko" Hospital of Thessaloniki
Thessaloniki, Greece
"Theagenion" Anticancer Hospital of Thessaloniki
Thessaloniki, Greece

Sponsors and Collaborators

Hellenic Oncology Research Group

University Hospital of Crete

Investigators

Principal Investigator:	Vassilis Georgoulias, MD	University Hospital of Crete
Principal Investigator:	Athanasios Kotsakis, MD	University Hospital of Crete

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kotsakis A, Agelaki S, Vardakis N, Stathopoulos G, Vamvakas L, Kalykaki A, Kentepozidis N, Kontopodis E, Sfakiotaki G, Mavroudis D, Georgoulias V. A dose-escalation study of pemetrexed and docetaxel in non-small-cell lung cancer. Cancer Chemother Pharmacol. 2011 Aug;68(2):415-22. doi: 10.1007/s00280-010-1508-5. Epub 2010 Nov 11.

Responsible Party:	V.Georgoulias, University Hospital of Crete
ClinicalTrials.gov Identifier:	NCT00684099 History of Changes
Other Study ID Numbers:	CT/05.18
First Posted:	May 26, 2008
Last Update Posted:	December 15, 2009
Last Verified:	December 2009

Keywords provided by Hellenic Oncology Research Group:

NSCLC; Pemetrexed; Docetaxel

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms	Docetaxel; Pemetrexed; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors