Ignite Creation Date:
2024-05-05 @ 4:35 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00270582
Status:
UNKNOWN
Last Update Posted:
2009-02-09
First Post:
2005-12-26
Brief Title:
A Study of Weekly Docetaxel Plus Cisplatin Followed by Gemcitabine vs Gemcitabine Plus Cisplatin Followed by Weekly Docetaxel in the Treatment of Advanced Non-Small-Cell Lung Cancer
Sponsor:
Far Eastern Memorial Hospital
Organization:
Far Eastern Memorial Hospital
Study Overview
Official Title:
A Randomized Phase II Study of Weekly Docetaxel Plus Cisplatin Followed by Gemcitabine vs Gemcitabine Plus Cisplatin Followed by Weekly Docetaxel in the Treatment of Advanced Non-Small Cell Lung Cancer
Status:
UNKNOWN
Status Verified Date:
2005-09
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Primary to evaluate the 1-year treatment failure rate of two sequential chemotherapy regimens
1 weekly docetaxel plus cisplatin followed by gemcitabine and
2 gemcitabine plus cisplatin followed by weekly docetaxel Study designProspective multi-center open-labelled randomized phase II study
1 weekly docetaxel plus cisplatin followed by gemcitabine and
2 gemcitabine plus cisplatin followed by weekly docetaxel Study designProspective multi-center open-labelled randomized phase II study
Detailed Description:
Lung cancer is the leading cause of cancer death in men and women worldwide Shifting trends in the incidence of lung cancer closely follow the patterns of cigarette smoking although other carcinogens have been implicated Despite intensive over the past several decades the 5-yr lung-cancer survival rate remains a dismal 8-14
Although lung cancer is not the most common cancer as the leading cause of cancer-related deaths in men and women it is the most deadly American Cancer Society 2000 Lung cancer is also the leading cause of cancer deaths in Taiwan According to the vital statistics of Department of Health in Taiwan the incidence of lung cancer is rank of 5th However the rank of cancer fatality is the second and first in men and women respectively The mortality of lung cancer have significant increasing trend in men and women during the two-decade period There are 6555 persons die for lung cancer in 2001
There is only 25 of cases resectable when diagnosed and only 1518 of cases can be surgical removed The postoperative recurrence rate and metastasis rate are also high for NSCLC Chemotherapy is used primarily to palliate disease symptoms and prolong survival in patients with unresectable disease stage IIIB and IV However overall survival benefit is modest
Gemcitabine has shown good activity in NSCLC both as a single agent and in combination with various other cytotoxic drugs Eli Lilly and Company 1999 A number of phase I and II studies in NSCLC have shown good safety and efficacy of two-drug combinations of Gemcitabine with agents other than cisplatin including carboplatin paclitaxel vinorelbine and docetaxel Eli Lilly and Company 1999
Gemcitabine plus cisplatin GC is one of the most active regimens in the treatment fir stage IIIBIV NSCLC patients In phase II studies 26-54 stage IIIBIV NSCLC patients respond to GC treatment Good median and 1-year survival have been consistently observed Abratt et al 1997 Crino et al 1997 Einhorn 1997 Shepherd et al 1997 In randomized phase III studies GC demonstrated the superior survival versus cisplatin alone Sandler A et al 2000 significantly higher response rate versus a three-drug combination of cisplatin mitomycin C and ifosfamideb Crino L et al 1999
Schiller JH et al conducted a randomized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer Schiller JH et al 2000 Patients with advanced non-small-cell lung cancer were randomly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens cisplatin and gemcitabine cisplatin and docetaxel or carboplatin and paclitaxel However none of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer GC provided longer time to progression than other three regimens
Abratt et al 1997 used GC in stage IIIBIV patients delivering cisplatin on day 15 resulted in goodresponse rate 52 median survival 13 months associated with low haematological toxicity and very few dose modifications of either gemicitabine or ciplatin This schedule seems to be feasible for induction treatment
Docetaxel plus cisplatin is one of options of front line treatment TAX326- a phase III trial studied docetaxel cisplatin or carboplatin vs vinorelbinecisplatin VC as first-line therapy for advanced non-small cell lung cancer NSCLC The schedule of chemotherapy was 75 mgm² of docetaxel followed by 75 mgm² of cisplatin repeated every 3 weeks and Vinorelbine 25 mgm2 IV day 1 8 15 22 and Cisplatin 100 mgm2 IV day 1 every 4 weeks The overall response rate were 32 docetaxelcisplatin and 25VC Docetaxel plus cisplatin showed survival benefit compared to VC 1-year survival rate 46 vs 41
Several phase II trials have investigated the efficacy and safety of Gemcitabine as a single agent second-line therapy Table below summarizes the results of the phase II trialsThese trials concluded that gemcitabine has a modest activity as second-line chemotherapy for NSCLC It has the advantage to be well tolerated and may thus be one drug to be proposed to the patients who have disease progression after a first-line chemotherapy and who ask for further treatment
In the initial development of docetaxel and paclitaxel these drugs routinely were administered once every 3 weeks However weekly administration of both these agents appears to offer several advantages in terms of toxicity Both agents can be administered weekly with markedly decreased myelosuppression while maintaining the same or increased dose intensity Fennelly D et al 1997 Seidman AD et al 1998 Hainsworth JD et al 1998
A Phase I trial demonstrated that docetaxel could be administered weekly at a maximum tolerated dose of 43 mgm2week with fatigue and asthenia as the dose-limiting toxicities Hainsworth JD et al 1998 At a weekly dose of 36 mgm2 docetaxel was extremely well tolerated with no significant myelosuppression and only occasional NCIC-CTG Grade 3 or 4 non-hematologic toxicities The recommended dose was 36 mgm2
Four clinical studies of single-agent weekly docetaxel in patients with NSCLC have been reported As second-line therapy for NSCLC weekly docetaxel has been studied by 3 groups Baylor-Charles 2000 Serke M et al 2001 Garcia-Lopez JL et al 2000 and Hainsworth JD and his colleagues studied weekly docetaxel as first-line treatment of NSCLC Hainsworth JD et al 2000
The 3 studies of weekly docetaxel as a single agent second-line consistently demonstrated efficacy and similar toxicity profiles Objective response rates ranged from 11 to 267 and the percentage of patients who responded or maintained stable disease ranged from 375 to 667 Docetaxel was generally well tolerated in each study
Weekly docetaxel is being studied in combination with other commonly used NSCLC chemotherapeutic agents including carboplatin navelbine and gemcitabine These combinations are being studied in both first- and second-line settings Second line chemotherapy with docetaxel may affect survival TAX 318 1 year survival 37 vs 11 However the optimal sequence of chemotherapy was rarely explored Weekly docetaxel may offer better tolerability vs 3-weekly schedule when combining docetaxel to cisplatin Based upon these studied we choose weekly docetaxel in combination with cisplatin as our regimen We expected the regimen would be effective and well tolerated
Based on the data above this study proposed to compare the efficacy and safety of the two regimens weekly docetaxel plus cisplatin followed by gemcitabine vs gemcitabine plus cisplatin followed by weekly docetaxel in metastatic of locally advanced non-small cell lung cancer
Although lung cancer is not the most common cancer as the leading cause of cancer-related deaths in men and women it is the most deadly American Cancer Society 2000 Lung cancer is also the leading cause of cancer deaths in Taiwan According to the vital statistics of Department of Health in Taiwan the incidence of lung cancer is rank of 5th However the rank of cancer fatality is the second and first in men and women respectively The mortality of lung cancer have significant increasing trend in men and women during the two-decade period There are 6555 persons die for lung cancer in 2001
There is only 25 of cases resectable when diagnosed and only 1518 of cases can be surgical removed The postoperative recurrence rate and metastasis rate are also high for NSCLC Chemotherapy is used primarily to palliate disease symptoms and prolong survival in patients with unresectable disease stage IIIB and IV However overall survival benefit is modest
Gemcitabine has shown good activity in NSCLC both as a single agent and in combination with various other cytotoxic drugs Eli Lilly and Company 1999 A number of phase I and II studies in NSCLC have shown good safety and efficacy of two-drug combinations of Gemcitabine with agents other than cisplatin including carboplatin paclitaxel vinorelbine and docetaxel Eli Lilly and Company 1999
Gemcitabine plus cisplatin GC is one of the most active regimens in the treatment fir stage IIIBIV NSCLC patients In phase II studies 26-54 stage IIIBIV NSCLC patients respond to GC treatment Good median and 1-year survival have been consistently observed Abratt et al 1997 Crino et al 1997 Einhorn 1997 Shepherd et al 1997 In randomized phase III studies GC demonstrated the superior survival versus cisplatin alone Sandler A et al 2000 significantly higher response rate versus a three-drug combination of cisplatin mitomycin C and ifosfamideb Crino L et al 1999
Schiller JH et al conducted a randomized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer Schiller JH et al 2000 Patients with advanced non-small-cell lung cancer were randomly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens cisplatin and gemcitabine cisplatin and docetaxel or carboplatin and paclitaxel However none of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer GC provided longer time to progression than other three regimens
Abratt et al 1997 used GC in stage IIIBIV patients delivering cisplatin on day 15 resulted in goodresponse rate 52 median survival 13 months associated with low haematological toxicity and very few dose modifications of either gemicitabine or ciplatin This schedule seems to be feasible for induction treatment
Docetaxel plus cisplatin is one of options of front line treatment TAX326- a phase III trial studied docetaxel cisplatin or carboplatin vs vinorelbinecisplatin VC as first-line therapy for advanced non-small cell lung cancer NSCLC The schedule of chemotherapy was 75 mgm² of docetaxel followed by 75 mgm² of cisplatin repeated every 3 weeks and Vinorelbine 25 mgm2 IV day 1 8 15 22 and Cisplatin 100 mgm2 IV day 1 every 4 weeks The overall response rate were 32 docetaxelcisplatin and 25VC Docetaxel plus cisplatin showed survival benefit compared to VC 1-year survival rate 46 vs 41
Several phase II trials have investigated the efficacy and safety of Gemcitabine as a single agent second-line therapy Table below summarizes the results of the phase II trialsThese trials concluded that gemcitabine has a modest activity as second-line chemotherapy for NSCLC It has the advantage to be well tolerated and may thus be one drug to be proposed to the patients who have disease progression after a first-line chemotherapy and who ask for further treatment
In the initial development of docetaxel and paclitaxel these drugs routinely were administered once every 3 weeks However weekly administration of both these agents appears to offer several advantages in terms of toxicity Both agents can be administered weekly with markedly decreased myelosuppression while maintaining the same or increased dose intensity Fennelly D et al 1997 Seidman AD et al 1998 Hainsworth JD et al 1998
A Phase I trial demonstrated that docetaxel could be administered weekly at a maximum tolerated dose of 43 mgm2week with fatigue and asthenia as the dose-limiting toxicities Hainsworth JD et al 1998 At a weekly dose of 36 mgm2 docetaxel was extremely well tolerated with no significant myelosuppression and only occasional NCIC-CTG Grade 3 or 4 non-hematologic toxicities The recommended dose was 36 mgm2
Four clinical studies of single-agent weekly docetaxel in patients with NSCLC have been reported As second-line therapy for NSCLC weekly docetaxel has been studied by 3 groups Baylor-Charles 2000 Serke M et al 2001 Garcia-Lopez JL et al 2000 and Hainsworth JD and his colleagues studied weekly docetaxel as first-line treatment of NSCLC Hainsworth JD et al 2000
The 3 studies of weekly docetaxel as a single agent second-line consistently demonstrated efficacy and similar toxicity profiles Objective response rates ranged from 11 to 267 and the percentage of patients who responded or maintained stable disease ranged from 375 to 667 Docetaxel was generally well tolerated in each study
Weekly docetaxel is being studied in combination with other commonly used NSCLC chemotherapeutic agents including carboplatin navelbine and gemcitabine These combinations are being studied in both first- and second-line settings Second line chemotherapy with docetaxel may affect survival TAX 318 1 year survival 37 vs 11 However the optimal sequence of chemotherapy was rarely explored Weekly docetaxel may offer better tolerability vs 3-weekly schedule when combining docetaxel to cisplatin Based upon these studied we choose weekly docetaxel in combination with cisplatin as our regimen We expected the regimen would be effective and well tolerated
Based on the data above this study proposed to compare the efficacy and safety of the two regimens weekly docetaxel plus cisplatin followed by gemcitabine vs gemcitabine plus cisplatin followed by weekly docetaxel in metastatic of locally advanced non-small cell lung cancer
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None