Ignite Creation Date:
2024-05-05 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00148122
Status:
COMPLETED
Last Update Posted:
2014-04-17
First Post:
2005-09-02
Brief Title:
A Study of a New Combination and Schedule of Chemotherapy Drugs for the Treatment of Head and Neck Cancer
Sponsor:
University of Michigan Rogel Cancer Center
Organization:
University of Michigan Rogel Cancer Center
Study Overview
Official Title:
A Phase II Trial Evaluating Weekly Docetaxel and Capecitabine in Patients With Metastatic or Advanced Locally Recurrent Head and Neck Cancer
Status:
COMPLETED
Status Verified Date:
2014-03
Last Known Status:
None
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:
The purpose of this study is to determine the effectiveness and side effects of a new combination and schedule of chemotherapy drugs in the treatment of head and neck cancer Patients with advanced or recurrent head and neck cancer which is untreatable by surgery or radiation therapy are eligible for this study Standard treatment for advanced or recurrent head and neck cancer involves the use of chemotherapy
Detailed Description:
Approximately 28900 patients will be diagnosed with squamous cell cancers of the oral cavity and pharynx in the year 2002 Of these an estimated 7400 patients will present with metastases or develop recurrent disease which is not amenable to surgery or radiation therapy Palliative chemotherapy is thus the only treatment option Currently combinations of cisplatin and 5-fluorouracil are used as first line treatment strategies with median times to progression of 25 to 3 months and median survival rates of 5 to 7 months The time to achieve maximum response with combination therapy is on average 4 months
Taxanes with their unique mechanism of microtubule stabilization have demonstrated response rates similar to standard first line combination regimens Several phase II studies have evaluated the efficacy of single agent docetaxel in head and neck cancer patients Cumulative response rates were approximately 30 with higher response rates observed in patients receiving no prior chemotherapy Docetaxel has also been used in combination with cisplatin and cisplatin and 5-fluorouracil Although response rates with such combination regimens were superior to the use of single agent docetaxel grade 3 and 4 toxicities were also more prevalent
Capecitabine Xeloda a fluoropyrimidine carbamate is an oral prodrug which is converted in tumor tissues to 5-fluorouracil through multienzymatic activation Capecitabine Xeloda has documented activity in breast and colorectal cancers and is widely administered Because 5-fluorouracil has efficacy in the treatment of head and neck cancer it is reasonable to consider that such tumors will respond to capecitabine To date there are no published trials using capecitabine Xeloda in the treatment of metastatic head and neck cancer patients However clinical trials are ongoing in the US and Europe with promising results
In preclinical models a synergistic interaction between capecitabine and docetaxel has been documented One possible explanation for the synergy is that docetaxel up-regulates tumor levels of thymidine phosphorylase the enzyme essential for the activation of capecitabine and 5-dFUrd to 5-fluorouracil Clinically OShaughnessy et al recently reported improved survival with docetaxelcapecitabine combination therapy in patients with metastatic breast cancer who previously failed anthracycline-containing chemotherapy In this phase III study patients were stratified according to previous exposure to paclitaxel and then randomized to capecitabine Xeloda 1250 mgm2 twice daily days 1-14 plus docetaxel 75 mgm2 day 1 repeated every 21 days versus docetaxel alone Grade 3 and 4 toxicities were more common in the docetaxelcapecitabine combination arm Capecitabine Xeloda and docetaxel were interrupted and the dosages reduced by 25 in patients who experienced a second occurrence of a given grade 2 toxicity or any grade 3 toxicity suggesting that the starting dosages were perhaps too high
The role of chemotherapy in metastatic head and neck cancer is limited to palliation of the symptoms of disease Platinum and 5-fluorouracil combinations remain standard first line treatment strategies The taxanes have been shown to have similar efficacy to such first line regimens and are often used as salvage treatment for patients with metastatic disease Given that docetaxel has documented clinical efficacy in head and neck cancer and that there are preclinical data to suggest synergy with docetaxel and capecitabine it is reasonable to consider using these agents in combination to treat head and neck cancer patients Moreover capecitabine and docetaxel have distinct mechanisms of action and no overlap of key toxicities A recent phase III study by Tonkin et al in metastatic breast cancer patients demonstrated activity and less toxicity when docetaxel 30 mgm2week day 1 and 8 q21 days was combined with capecitabine 1800 mgm2day 14 of 21 days In another phase I study by Nadella et al weekly docetaxel 36 mgm2 was combined with 14 days of capecitabine up to 1500 mgm2day over a course of 28 days Antitumor responses were observed in patients with breast colon and bladder cancers Hence we propose this study whereby patients with previously treated metastaticrecurrent head and neck cancer will receive treatment with docetaxel and capecitabine
To reduce the potential for toxicity we will use a modification of the Nadella regimen Docetaxel will be administered weekly at a dosage of 30 mgm2 for 3 out of every 4 weeks and capecitabine will be administered at a flat dosage of 2000 mg per day 1000 mg po bid for two weeks out of every 4 weeks The justification for using a flat dosage of capecitabine versus a calculated dosage is based on pharmacokinetic data that show no change in clearance of capecitabine with changes in BSA We plan to use a fixed dose of 2000 mg qd 1000 mg q am and 1000 mg q pm Fixed dosing of capecitabine is convenient and feasible as shown in a prior University of Michigan study in breast cancer patients In another study Schott et al informally piloted the combination of weekly docetaxel 36 mgm2 and 1500 mg twice daily 3000 mgday x 14 days capecitabine in metastatic breast cancer patients and found it to be without unexpected or untoward side effects Additionally to take advantage of the time course of upregulation of TP in the preclinical models the capecitabine dose will be given on days 5-18 In a flat dosing scheme the Nadella regimen would have administered an average dose of 2125 mg qd for 14 days assuming an average BSA of 17 m2 We plan to round this dosage downward to 2000 mg per day x 14 days therefore our regimen will use a slightly lower dosage of capecitabine We feel that our proposed slightly lowered dose closer to Nadella phase I dosing vs Tonkin of capecitabine is justified for the following reasons
1 The Nadella study was performed in a group of patients with solid tumor malignancies that were refractory to conventional therapy or for whom no effective therapy existed ECOG performance status PS was 1 or 2 in 517 30 patients 1017 patients had received 2 or more lines of previous chemotherapy and 717 patients had received previous radiotherapy Based on data from previous treatment of head and neck cancer patients at the University of Michigan the patient population to be enrolled in this trial is expected to be 60 PS 0 and 40 PS 1 and some will have received prior chemotherapy andor radiotherapy Like the Nadella patient population a majority of our patients have been pretreated and are of poorer health
2 Dose interruptions and modifications are built into the protocol so that appropriate changes in treatment can be made in patients with Grade I or II toxicity before the toxicity becomes Grade III or greater Since the docetaxel is given weekly and the capecitabine is administered daily if patients are experiencing toxicity within a cycle the dose of either can be held or modified
Taxanes with their unique mechanism of microtubule stabilization have demonstrated response rates similar to standard first line combination regimens Several phase II studies have evaluated the efficacy of single agent docetaxel in head and neck cancer patients Cumulative response rates were approximately 30 with higher response rates observed in patients receiving no prior chemotherapy Docetaxel has also been used in combination with cisplatin and cisplatin and 5-fluorouracil Although response rates with such combination regimens were superior to the use of single agent docetaxel grade 3 and 4 toxicities were also more prevalent
Capecitabine Xeloda a fluoropyrimidine carbamate is an oral prodrug which is converted in tumor tissues to 5-fluorouracil through multienzymatic activation Capecitabine Xeloda has documented activity in breast and colorectal cancers and is widely administered Because 5-fluorouracil has efficacy in the treatment of head and neck cancer it is reasonable to consider that such tumors will respond to capecitabine To date there are no published trials using capecitabine Xeloda in the treatment of metastatic head and neck cancer patients However clinical trials are ongoing in the US and Europe with promising results
In preclinical models a synergistic interaction between capecitabine and docetaxel has been documented One possible explanation for the synergy is that docetaxel up-regulates tumor levels of thymidine phosphorylase the enzyme essential for the activation of capecitabine and 5-dFUrd to 5-fluorouracil Clinically OShaughnessy et al recently reported improved survival with docetaxelcapecitabine combination therapy in patients with metastatic breast cancer who previously failed anthracycline-containing chemotherapy In this phase III study patients were stratified according to previous exposure to paclitaxel and then randomized to capecitabine Xeloda 1250 mgm2 twice daily days 1-14 plus docetaxel 75 mgm2 day 1 repeated every 21 days versus docetaxel alone Grade 3 and 4 toxicities were more common in the docetaxelcapecitabine combination arm Capecitabine Xeloda and docetaxel were interrupted and the dosages reduced by 25 in patients who experienced a second occurrence of a given grade 2 toxicity or any grade 3 toxicity suggesting that the starting dosages were perhaps too high
The role of chemotherapy in metastatic head and neck cancer is limited to palliation of the symptoms of disease Platinum and 5-fluorouracil combinations remain standard first line treatment strategies The taxanes have been shown to have similar efficacy to such first line regimens and are often used as salvage treatment for patients with metastatic disease Given that docetaxel has documented clinical efficacy in head and neck cancer and that there are preclinical data to suggest synergy with docetaxel and capecitabine it is reasonable to consider using these agents in combination to treat head and neck cancer patients Moreover capecitabine and docetaxel have distinct mechanisms of action and no overlap of key toxicities A recent phase III study by Tonkin et al in metastatic breast cancer patients demonstrated activity and less toxicity when docetaxel 30 mgm2week day 1 and 8 q21 days was combined with capecitabine 1800 mgm2day 14 of 21 days In another phase I study by Nadella et al weekly docetaxel 36 mgm2 was combined with 14 days of capecitabine up to 1500 mgm2day over a course of 28 days Antitumor responses were observed in patients with breast colon and bladder cancers Hence we propose this study whereby patients with previously treated metastaticrecurrent head and neck cancer will receive treatment with docetaxel and capecitabine
To reduce the potential for toxicity we will use a modification of the Nadella regimen Docetaxel will be administered weekly at a dosage of 30 mgm2 for 3 out of every 4 weeks and capecitabine will be administered at a flat dosage of 2000 mg per day 1000 mg po bid for two weeks out of every 4 weeks The justification for using a flat dosage of capecitabine versus a calculated dosage is based on pharmacokinetic data that show no change in clearance of capecitabine with changes in BSA We plan to use a fixed dose of 2000 mg qd 1000 mg q am and 1000 mg q pm Fixed dosing of capecitabine is convenient and feasible as shown in a prior University of Michigan study in breast cancer patients In another study Schott et al informally piloted the combination of weekly docetaxel 36 mgm2 and 1500 mg twice daily 3000 mgday x 14 days capecitabine in metastatic breast cancer patients and found it to be without unexpected or untoward side effects Additionally to take advantage of the time course of upregulation of TP in the preclinical models the capecitabine dose will be given on days 5-18 In a flat dosing scheme the Nadella regimen would have administered an average dose of 2125 mg qd for 14 days assuming an average BSA of 17 m2 We plan to round this dosage downward to 2000 mg per day x 14 days therefore our regimen will use a slightly lower dosage of capecitabine We feel that our proposed slightly lowered dose closer to Nadella phase I dosing vs Tonkin of capecitabine is justified for the following reasons
1 The Nadella study was performed in a group of patients with solid tumor malignancies that were refractory to conventional therapy or for whom no effective therapy existed ECOG performance status PS was 1 or 2 in 517 30 patients 1017 patients had received 2 or more lines of previous chemotherapy and 717 patients had received previous radiotherapy Based on data from previous treatment of head and neck cancer patients at the University of Michigan the patient population to be enrolled in this trial is expected to be 60 PS 0 and 40 PS 1 and some will have received prior chemotherapy andor radiotherapy Like the Nadella patient population a majority of our patients have been pretreated and are of poorer health
2 Dose interruptions and modifications are built into the protocol so that appropriate changes in treatment can be made in patients with Grade I or II toxicity before the toxicity becomes Grade III or greater Since the docetaxel is given weekly and the capecitabine is administered daily if patients are experiencing toxicity within a cycle the dose of either can be held or modified
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| Legacy IRBMED 2002-747 | OTHER | University of Michigan IRBMED | None |