Ignite Creation Date:
2024-05-05 @ 4:47 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00319839
Status:
TERMINATED
Last Update Posted:
2018-01-12
First Post:
2006-04-27
Brief Title:
Study of Albumin Bound-Paclitaxel for Treatment of Recurrent or Metastatic Head and Neck Cancer With Cetuximab
Sponsor:
University of California Irvine
Organization:
University of California Irvine
Study Overview
Official Title:
A Phase II Study of Albumin Bound-Paclitaxel AbraxaneTM for Treatment of Recurrent or Metastatic Head and Neck Cancer With the Addition of Cetuximab Erbitux IMC-225 on Disease Progression
Status:
TERMINATED
Status Verified Date:
2018-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
slow accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Primary Objective To assess the overall response rate complete and partial response to Abraxane in patients with recurrent or metastatic head and neck cancer with the addition of Cetuximab on disease progression
Approximately 40000 new cases of head and neck cancer are diagnosed annually in the United States Jemal et al 2003 and over 30 of these patients are expected to die of their malignancy Squamous cell carcinoma accounts for more than 90 of head and neck cancer cases Although metastatic disease at the time of diagnosis is rather uncommon and despite aggressive use of up-front concurrent radiation and cisplatin-based chemotherapy approximately 20 of the patients will develop metastases Patients with recurrent or metastatic squamous cell carcinoma of the head and neck SCCHN have a poor prognosis
A subsequent randomized study conducted by ECOG E1393 compared high-dose paclitaxel 200 mgm2 as a 24-hour infusion plus cisplatin 75 mgm2 with G-CSF support to low dose paclitaxel 135 mgm2 as a 24-hour infusion plus cisplatin 75 mgm2 Forastiere et al 2001 Patients with newly diagnosed metastatic or recurrent squamous cell carcinoma of the head and neck excluding nasopharyngeal primaries were eligible No prior treatment for recurrentmetastatic disease was allowed but patients could have received chemotherapy as a part of the initial curative therapy that should have been completed 6 months prior to study
No statistically significant difference could be demonstrated either in response rates or survival between the two arms Murphy et al 2001 This study however indicated that paclitaxel a member of the taxane class of anti-tumor agent is active in head and neck cancer
New agents to treat head and neck cancer need to be investigated Abraxane an albumin-bound formulation of paclitaxel has shown significant single-agent activity in breast cancer and in head and neck cancer Recently Abraxane has approved for use in metastatic breast cancer Given previous randomized phase III trials indicated single agent chemotherapy fared as well as combination chemotherapy regimen in terms of overall survival this novel formulation should be actively investigated in head and neck cancer
Approximately 40000 new cases of head and neck cancer are diagnosed annually in the United States Jemal et al 2003 and over 30 of these patients are expected to die of their malignancy Squamous cell carcinoma accounts for more than 90 of head and neck cancer cases Although metastatic disease at the time of diagnosis is rather uncommon and despite aggressive use of up-front concurrent radiation and cisplatin-based chemotherapy approximately 20 of the patients will develop metastases Patients with recurrent or metastatic squamous cell carcinoma of the head and neck SCCHN have a poor prognosis
A subsequent randomized study conducted by ECOG E1393 compared high-dose paclitaxel 200 mgm2 as a 24-hour infusion plus cisplatin 75 mgm2 with G-CSF support to low dose paclitaxel 135 mgm2 as a 24-hour infusion plus cisplatin 75 mgm2 Forastiere et al 2001 Patients with newly diagnosed metastatic or recurrent squamous cell carcinoma of the head and neck excluding nasopharyngeal primaries were eligible No prior treatment for recurrentmetastatic disease was allowed but patients could have received chemotherapy as a part of the initial curative therapy that should have been completed 6 months prior to study
No statistically significant difference could be demonstrated either in response rates or survival between the two arms Murphy et al 2001 This study however indicated that paclitaxel a member of the taxane class of anti-tumor agent is active in head and neck cancer
New agents to treat head and neck cancer need to be investigated Abraxane an albumin-bound formulation of paclitaxel has shown significant single-agent activity in breast cancer and in head and neck cancer Recently Abraxane has approved for use in metastatic breast cancer Given previous randomized phase III trials indicated single agent chemotherapy fared as well as combination chemotherapy regimen in terms of overall survival this novel formulation should be actively investigated in head and neck cancer
Detailed Description:
OBJECTIVES
Primary Objective To assess the overall response rate complete and partial response to Abraxane in patients with recurrent or metastatic head and neck cancer with the addition of Cetuximab on disease progression
Secondary Objectives 1 To assess the frequency and severity of toxicities associated with this treatment 2 To evaluate overall survival and progression-free survival in patients with recurrent or metastatic head and neck cancer treated with single agent Abraxane 3To assess whether the addition of Cetuximab will re-sensitize head and neck cancer to Abraxane after progression on single agent Abraxane
BACKGROUND AND RATIONALE
Approximately 40000 new cases of head and neck cancer are diagnosed annually in the United States Jemal et al 2003 and over 30 of these patients are expected to die of their malignancy Squamous cell carcinoma accounts for more than 90 of head and neck cancer cases Although metastatic disease at the time of diagnosis is rather uncommon and despite aggressive use of up-front concurrent radiation and cisplatin-based chemotherapy approximately 20 of the patients will develop metastases Patients with recurrent or metastatic squamous cell carcinoma of the head and neck SCCHN have a poor prognosis Their median survival is about 6-8 months Selected patients with locally recurrent disease can be treated with a curative intent with locoregional therapies such as salvage surgery or radiation De Crevoisier et al 1998 however the majority of these patients die of their disease Despite high response rates combination chemotherapy has not been shown to produce a survival benefit compared to single agents in randomized trials in patients with recurrentmetastatic head and neck cancer Forastiere et al 1992 Jacobs et al 1992 Clavel et al 1994 A phase III randomized study conducted by Southwest Oncology Group SWOG compared cisplatin-based combination chemotherapy to single agent methotrexate Forastiere et al 1992 The objective response rates were 32 21 and 10 for cisplatin5-Fluorouracil 5-FU carboplatin5-FU and single methotrexate respectively but the median overall survival was not statistically different between the three arms ranged between 5 to 66 months Moreover toxicity was increased with combination therapy especially with the cisplatin-based regimen Another randomized study conducted in the US demonstrated a significantly higher response rate of 32 for the combination of cisplatin and 5-FU versus 17 and 13 for single agent cisplatin and 5-FU respectively Jacobs et al 1992 However the median survival of all patients was 57 months with no difference between the three arms Hematologic toxicity was increased in the combination arm
A subsequent randomized study conducted by ECOG E1393 compared high-dose paclitaxel 200 mgm2 as a 24-hour infusion plus cisplatin 75 mgm2 with granulocyte-colony stimulating factor G-CSF support to low dose paclitaxel 135 mgm2 as a 24-hour infusion plus cisplatin 75 mgm2 Forastiere et al 2001 Patients with newly diagnosed metastatic or recurrent squamous cell carcinoma of the head and neck excluding nasopharyngeal primaries were eligible No prior treatment for recurrentmetastatic disease was allowed but patients could have received chemotherapy as a part of the initial curative therapy that should have been completed 6 months prior to study Tow hundred and ten patients were randomized between the 2 arms No significant difference in outcome was observed The response rate was 35 vs 36 and the median survival was 76 vs 68 months in the high-dose vs low-dose paclitaxel arms respectively Patients with metastatic disease performed worse in terms of survival Previously untreated patients achieved a higher response rate of 58 compared to a response rate of 32 observed in patients who have failed prior curative therapies Substantial toxicities were observed in this trial Grade 4 neutropenia was seen in 61-71 of patients and febrile neutropenia with hospitalization occurred in 27-39 of patients The toxic death rate was 10 12 vs 9 Forastiere et al 2001 It was concluded that the 24-hour paclitaxel infusion was associated with unacceptable toxicity when combined with cisplatin Instead a 3-hour paclitaxel infusion combined with cisplatin was advanced to further testing A more recent randomized trial conducted by ECOG E1395 compared the combination of paclitaxel 175 mgm2 as a 3-hour infusion and cisplatin 75 mgm2 to a standard cisplatin and 5-FU regimen No statistically significant difference could be demonstrated either in response rates or survival between the two arms Murphy et al 2001 This study however indicated that paclitaxel a member of the taxane class of anti-tumor agent is active in head and neck cancer
Recently another member anti-tumor class of taxane Docetaxel Taxotere has been shown to be active in advanced head and neck cancer In a randomized phase III trial of intensification of induction chemotherapy followed by radiation the addition of docetaxel to the induction regimen of cisplatin and 5-fluoruracil when compared to cisplatin and 5-fluoruracil alone resulted in a 3-month improvement in overall survival Vermorken et al 2004 Thus both members of the taxane family paclitaxel and docetaxel have proven anti-tumor activity in head and neck cancer
New agents to treat head and neck cancer need to be investigated Abraxane an albumin-bound formulation of paclitaxel has shown significant single-agent activity in breast cancer and in head and neck cancer Recently Abraxane has approved for use in metastatic breast cancer Given previous randomized phase III trials indicated single agent chemotherapy fared as well as combination chemotherapy regimen in terms of overall survival this novel formulation should be actively investigated in head and neck cancer
Abraxane in solid tumor The clinical database included two single arm studies enrolling a total of 106 patients and one multi-center randomized trial The multi-center trial was conducted in 460 patients with metastatic breast cancer who were randomized to receive either Abraxane 260 mgm² administered as a 30-minute infusion or paclitaxel 175 mgm² given over 3 hours Sixty-four percent of patients had impaired performance status ECOG 1 or 2 at study entry Seventy-nine percent had visceral metastases and 76 had 3 sites of metastases Fifty-nine percent of patients had received one or more prior chemotherapy regimens and 77 had received an anthracycline-containing regimen The objective response rate verified by central review was 215 95 Confidence interval CI 162 to 267 for Abraxane compared to 111 95 CI 69 to 151 for paclitaxel p0003 The conclusion of this phase III trial is that Abraxane had statistically significant higher target lesion response rate the trial primary endpoint OShaughnessy et al 2003
On January 7 2005 the U S Food and Drug Administration approved Abraxane albumin-bound paclitaxel for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy based on the statistically significant superior response rate from the randomized phase III trial mentioned above The recommended dose of Abraxane is 260 mgm² administered intravenously over 30 minutes every 3 weeks No premedication to prevent hypersensitivity reactions is required prior to Abraxane administration
Abraxane in Head and Neck Cancer The role of Abraxane in Head and Neck cancer has been explored in a phase I study Damascelli et al 2001 Abraxane was injected intra-arterially carotid artery in 31 patients with advanced Head and Neck cancer The maximum tolerated dose in a single administration was determined to be 270 mgm2 which is very close to the approved dose of 260 mgm2 Three patients achieved complete response and 19 patients achieved partial response for a combined response rate of 76 Side effects are very tolerable including three patients with grade 4 neutropenia and grade 2 non-hematologic toxicities included keratitis 1 patient skin toxicity 5 patients neurologic toxicities 4 patients and flu-like syndrome 7 patients However intra-arterial administration is technically challenging with potential serious side effects cumbersome and not the conventional way of delivering chemotherapy In another phase 1 study of Abraxane in advanced solid tumors 3 out of 5 patients with nasopharyngeal carcinoma had responses lasting 25 18 and 13 weeks Teng et al 2005
Given the hint of anti-tumor activity of Abraxane in advanced Head and Neck cancer from the above mentioned studies this current study will seek to determine the efficacy of Abraxane in recurrent or metastatic head and neck cancer at the dose of 260 mgm2 given intravenously every 3 weeks in a systemic manner Abraxane is not FDA approved in the treatment of this study disease however it is approved for patient use in the treatment of advanced breast cancer that have failed traditional therapy
Abraxane is a natural substance and is far more superior to conventional chemistry Abraxane is an effective treatment for aggressive cancers because it adversely affects the process of cell division by preventing this restructuring Other cells are also affected adversely but since cancer cells divide much faster than non-cancerous cells they are far more susceptible to Abraxane treatment thus the safety of the drug is no more or less then other chemotherapy regimens
Human albumin will be used along with the Abraxane
Description of Cetuximab IMC-225 Erbitux NSC-714692 Cetuximab a chimerized antibody of the immunoglobulin gamma-1 IgG1 subclass was originally derived from a mouse myeloma cell line The chimerization resulted in an antibody with binding affinity to epidermal growth factor receptors EGFR greater than the natural ligand epidermal growth factor EGF Cetuximab blocks binding EGF and transforming growth factor TGFa to EGFR and inhibits ligand-induced activation of this tyrosine kinase receptor Cetuximab also stimulates EGFR internalization effectively removing the receptor from the cell surface for interaction with ligand
Safety Precaution Cetuximab therapy should be used with caution in patients with known hypersensitivity to Cetuximab murine proteins or any component of this product
Administration of Cetuximab In an effort to prevent a hypersensitivity reaction all patients should be premedicated with dexamethasone 20 mg by IV and diphenhydramine hydrochloride 50 mg by IV given 30-60 minutes prior to the infusion of cetuximab
The initialloading dose of cetuximab is 400 mgm2 IV administered over 120 minutes Patients must be continuously observed during the infusion for signs of anaphylaxis and standard resuscitative meds should be in close proximity Vital signs should be taken prior to during post and 1-hour post infusion for the initial dose For subsequent infusions vital signs are recommended to be taken to and 1-hour post infusion
Following the loading dose patients will receive weekly treatment with cetuximab IV over 60 minutes The infusion rate of cetuximab should never exceed 5 mLmin Patients should be closely monitored for treatment-related adverse events especially hypersensitivity reactions during the infusion and post-infusion
Cetuximab is used for the treatment of patients with advanced head and neck cancer that has spread to other parts of the body
Primary Objective To assess the overall response rate complete and partial response to Abraxane in patients with recurrent or metastatic head and neck cancer with the addition of Cetuximab on disease progression
Secondary Objectives 1 To assess the frequency and severity of toxicities associated with this treatment 2 To evaluate overall survival and progression-free survival in patients with recurrent or metastatic head and neck cancer treated with single agent Abraxane 3To assess whether the addition of Cetuximab will re-sensitize head and neck cancer to Abraxane after progression on single agent Abraxane
BACKGROUND AND RATIONALE
Approximately 40000 new cases of head and neck cancer are diagnosed annually in the United States Jemal et al 2003 and over 30 of these patients are expected to die of their malignancy Squamous cell carcinoma accounts for more than 90 of head and neck cancer cases Although metastatic disease at the time of diagnosis is rather uncommon and despite aggressive use of up-front concurrent radiation and cisplatin-based chemotherapy approximately 20 of the patients will develop metastases Patients with recurrent or metastatic squamous cell carcinoma of the head and neck SCCHN have a poor prognosis Their median survival is about 6-8 months Selected patients with locally recurrent disease can be treated with a curative intent with locoregional therapies such as salvage surgery or radiation De Crevoisier et al 1998 however the majority of these patients die of their disease Despite high response rates combination chemotherapy has not been shown to produce a survival benefit compared to single agents in randomized trials in patients with recurrentmetastatic head and neck cancer Forastiere et al 1992 Jacobs et al 1992 Clavel et al 1994 A phase III randomized study conducted by Southwest Oncology Group SWOG compared cisplatin-based combination chemotherapy to single agent methotrexate Forastiere et al 1992 The objective response rates were 32 21 and 10 for cisplatin5-Fluorouracil 5-FU carboplatin5-FU and single methotrexate respectively but the median overall survival was not statistically different between the three arms ranged between 5 to 66 months Moreover toxicity was increased with combination therapy especially with the cisplatin-based regimen Another randomized study conducted in the US demonstrated a significantly higher response rate of 32 for the combination of cisplatin and 5-FU versus 17 and 13 for single agent cisplatin and 5-FU respectively Jacobs et al 1992 However the median survival of all patients was 57 months with no difference between the three arms Hematologic toxicity was increased in the combination arm
A subsequent randomized study conducted by ECOG E1393 compared high-dose paclitaxel 200 mgm2 as a 24-hour infusion plus cisplatin 75 mgm2 with granulocyte-colony stimulating factor G-CSF support to low dose paclitaxel 135 mgm2 as a 24-hour infusion plus cisplatin 75 mgm2 Forastiere et al 2001 Patients with newly diagnosed metastatic or recurrent squamous cell carcinoma of the head and neck excluding nasopharyngeal primaries were eligible No prior treatment for recurrentmetastatic disease was allowed but patients could have received chemotherapy as a part of the initial curative therapy that should have been completed 6 months prior to study Tow hundred and ten patients were randomized between the 2 arms No significant difference in outcome was observed The response rate was 35 vs 36 and the median survival was 76 vs 68 months in the high-dose vs low-dose paclitaxel arms respectively Patients with metastatic disease performed worse in terms of survival Previously untreated patients achieved a higher response rate of 58 compared to a response rate of 32 observed in patients who have failed prior curative therapies Substantial toxicities were observed in this trial Grade 4 neutropenia was seen in 61-71 of patients and febrile neutropenia with hospitalization occurred in 27-39 of patients The toxic death rate was 10 12 vs 9 Forastiere et al 2001 It was concluded that the 24-hour paclitaxel infusion was associated with unacceptable toxicity when combined with cisplatin Instead a 3-hour paclitaxel infusion combined with cisplatin was advanced to further testing A more recent randomized trial conducted by ECOG E1395 compared the combination of paclitaxel 175 mgm2 as a 3-hour infusion and cisplatin 75 mgm2 to a standard cisplatin and 5-FU regimen No statistically significant difference could be demonstrated either in response rates or survival between the two arms Murphy et al 2001 This study however indicated that paclitaxel a member of the taxane class of anti-tumor agent is active in head and neck cancer
Recently another member anti-tumor class of taxane Docetaxel Taxotere has been shown to be active in advanced head and neck cancer In a randomized phase III trial of intensification of induction chemotherapy followed by radiation the addition of docetaxel to the induction regimen of cisplatin and 5-fluoruracil when compared to cisplatin and 5-fluoruracil alone resulted in a 3-month improvement in overall survival Vermorken et al 2004 Thus both members of the taxane family paclitaxel and docetaxel have proven anti-tumor activity in head and neck cancer
New agents to treat head and neck cancer need to be investigated Abraxane an albumin-bound formulation of paclitaxel has shown significant single-agent activity in breast cancer and in head and neck cancer Recently Abraxane has approved for use in metastatic breast cancer Given previous randomized phase III trials indicated single agent chemotherapy fared as well as combination chemotherapy regimen in terms of overall survival this novel formulation should be actively investigated in head and neck cancer
Abraxane in solid tumor The clinical database included two single arm studies enrolling a total of 106 patients and one multi-center randomized trial The multi-center trial was conducted in 460 patients with metastatic breast cancer who were randomized to receive either Abraxane 260 mgm² administered as a 30-minute infusion or paclitaxel 175 mgm² given over 3 hours Sixty-four percent of patients had impaired performance status ECOG 1 or 2 at study entry Seventy-nine percent had visceral metastases and 76 had 3 sites of metastases Fifty-nine percent of patients had received one or more prior chemotherapy regimens and 77 had received an anthracycline-containing regimen The objective response rate verified by central review was 215 95 Confidence interval CI 162 to 267 for Abraxane compared to 111 95 CI 69 to 151 for paclitaxel p0003 The conclusion of this phase III trial is that Abraxane had statistically significant higher target lesion response rate the trial primary endpoint OShaughnessy et al 2003
On January 7 2005 the U S Food and Drug Administration approved Abraxane albumin-bound paclitaxel for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy based on the statistically significant superior response rate from the randomized phase III trial mentioned above The recommended dose of Abraxane is 260 mgm² administered intravenously over 30 minutes every 3 weeks No premedication to prevent hypersensitivity reactions is required prior to Abraxane administration
Abraxane in Head and Neck Cancer The role of Abraxane in Head and Neck cancer has been explored in a phase I study Damascelli et al 2001 Abraxane was injected intra-arterially carotid artery in 31 patients with advanced Head and Neck cancer The maximum tolerated dose in a single administration was determined to be 270 mgm2 which is very close to the approved dose of 260 mgm2 Three patients achieved complete response and 19 patients achieved partial response for a combined response rate of 76 Side effects are very tolerable including three patients with grade 4 neutropenia and grade 2 non-hematologic toxicities included keratitis 1 patient skin toxicity 5 patients neurologic toxicities 4 patients and flu-like syndrome 7 patients However intra-arterial administration is technically challenging with potential serious side effects cumbersome and not the conventional way of delivering chemotherapy In another phase 1 study of Abraxane in advanced solid tumors 3 out of 5 patients with nasopharyngeal carcinoma had responses lasting 25 18 and 13 weeks Teng et al 2005
Given the hint of anti-tumor activity of Abraxane in advanced Head and Neck cancer from the above mentioned studies this current study will seek to determine the efficacy of Abraxane in recurrent or metastatic head and neck cancer at the dose of 260 mgm2 given intravenously every 3 weeks in a systemic manner Abraxane is not FDA approved in the treatment of this study disease however it is approved for patient use in the treatment of advanced breast cancer that have failed traditional therapy
Abraxane is a natural substance and is far more superior to conventional chemistry Abraxane is an effective treatment for aggressive cancers because it adversely affects the process of cell division by preventing this restructuring Other cells are also affected adversely but since cancer cells divide much faster than non-cancerous cells they are far more susceptible to Abraxane treatment thus the safety of the drug is no more or less then other chemotherapy regimens
Human albumin will be used along with the Abraxane
Description of Cetuximab IMC-225 Erbitux NSC-714692 Cetuximab a chimerized antibody of the immunoglobulin gamma-1 IgG1 subclass was originally derived from a mouse myeloma cell line The chimerization resulted in an antibody with binding affinity to epidermal growth factor receptors EGFR greater than the natural ligand epidermal growth factor EGF Cetuximab blocks binding EGF and transforming growth factor TGFa to EGFR and inhibits ligand-induced activation of this tyrosine kinase receptor Cetuximab also stimulates EGFR internalization effectively removing the receptor from the cell surface for interaction with ligand
Safety Precaution Cetuximab therapy should be used with caution in patients with known hypersensitivity to Cetuximab murine proteins or any component of this product
Administration of Cetuximab In an effort to prevent a hypersensitivity reaction all patients should be premedicated with dexamethasone 20 mg by IV and diphenhydramine hydrochloride 50 mg by IV given 30-60 minutes prior to the infusion of cetuximab
The initialloading dose of cetuximab is 400 mgm2 IV administered over 120 minutes Patients must be continuously observed during the infusion for signs of anaphylaxis and standard resuscitative meds should be in close proximity Vital signs should be taken prior to during post and 1-hour post infusion for the initial dose For subsequent infusions vital signs are recommended to be taken to and 1-hour post infusion
Following the loading dose patients will receive weekly treatment with cetuximab IV over 60 minutes The infusion rate of cetuximab should never exceed 5 mLmin Patients should be closely monitored for treatment-related adverse events especially hypersensitivity reactions during the infusion and post-infusion
Cetuximab is used for the treatment of patients with advanced head and neck cancer that has spread to other parts of the body
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 |
|---|---|---|---|
| 2005-4667 | OTHER | University of California Irvine | None |