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

Non Small Cell Lung Cancer Clinical Trial

Official title:

A Phase I/II Study Of The Docetaxel/Pemetrexed Combination As First Line Treatment In Patients With Advanced/Metastatic NSCLC

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00684099
• Other study ID #: CT/05.18
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 22, 2008
• Last updated: December 14, 2009
• Start date: May 2006
• Est. completion date: May 2009

Study information

• Verified date: December 2009
• Source: Hellenic Oncology Research Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Greece: National Organization of Medicines
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non Small Cell Lung Cancer

Intervention

Drug:
• Docetaxel
Docetaxel at starting dose of 65 mg/m2 IV on day 1 every 3 weeks for a total of 6 cycles
• Pemetrexed
Pemetrexed at starting dose of 400 mg/m2 IV on day 1 every 3 weeks for a total of 6 cycles

Locations

Country	Name	City	State
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

Sponsors (2)

Lead Sponsor	Collaborator
Hellenic Oncology Research Group	University Hospital of Crete

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of Dose Limited Toxicity and Maximum Tolerated Dose for the docetaxel/pemetrexed doublet		2 years	Yes
Secondary	Response rate for the docetaxel/pemetrexed doublet		2 years	No