Ignite Creation Date:
2024-05-05 @ 6:31 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00498953
Status:
COMPLETED
Last Update Posted:
2018-07-09
First Post:
2007-07-10
Brief Title:
Combination Chemotherapy and Radiation Therapy With or Without Lapatinib in Treating Patients With Locally Advanced Cancer of the Larynx or Hypopharynx
Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC
Organization:
European Organisation for Research and Treatment of Cancer - EORTC
Study Overview
Official Title:
Phase III Study on Induction Chemotherapy Followed by Chemoradiation With or Without Lapatinib a Dual EGFRErbB2 Kinase Inhibitor in Patients With Locally Advanced Larynx and Hypopharynx Squamous Cell Carcinoma
Status:
COMPLETED
Status Verified Date:
2018-07
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:
RATIONALE Drugs used in chemotherapy such as docetaxel cisplatin fluorouracil and carboplatin work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing Radiation therapy uses high-energy x-rays to kill tumor cells Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Giving combination chemotherapy together with radiation therapy with or without lapatinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed or eliminate the need for surgery
PURPOSE This phase III trial is studying the side effects and best dose of combination chemotherapy given together with radiation therapy with or without lapatinib and to see how well it works in treating patients with locally advanced cancer of the larynx or hypopharynx
PURPOSE This phase III trial is studying the side effects and best dose of combination chemotherapy given together with radiation therapy with or without lapatinib and to see how well it works in treating patients with locally advanced cancer of the larynx or hypopharynx
Detailed Description:
OBJECTIVES
Primary
Determine the maximum tolerated dose and recommended dose for phase II of lapatinib ditosylate in patients with locally advanced squamous cell carcinoma of the larynyx or hypopharynx who are concomitantly treated with neoadjuvant induction chemotherapy comprising docetaxel cisplatin and fluorouracil followed by chemoradiotherapy comprising carboplatin and radiotherapy Phase I
To document the feasibility in the framework of an organ preservation program of this regimen in these patients Phase II
Secondary
To look at the role of PET in patients with N1-3 disease in terms of PET being used as a reliable method to spare patients from planned neck dissection Phase II
OUTLINE This is a multicenter dose-escalation phase I study followed by a randomized phase II study Patients are stratified by institution and EGFR status negative vs positive
Phase I
Neoadjuvant chemotherapy Patients receive neoadjuvant chemotherapy comprising docetaxel IV and cisplatin IV on day 1 and fluorouracil IV continuously on days 1-5 Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity Patients with a complete or partial response after 4 courses of neoadjuvant chemotherapy proceed to chemoradiotherapy Patients with less than a partial response after course 2 or course 4 proceed to surgery including total laryngectomy
Chemoradiotherapy Within 3 weeks after completion of neoadjuvant chemotherapy patients undergo radiotherapy on days 1-5 8-12 15-19 22-26 29-33 36-40 and 43-47 and receive carboplatin IV on days 1 8 15 22 29 36 and 43
Concurrent lapatinib ditosylate Patients receive oral lapatinib ditosylate once daily during neoadjuvant chemotherapy during the break between neoadjuvant chemotherapy and chemoradiotherapy and during chemoradiotherapy
Phase II Patients are randomized to 1 of 2 treatment arms
Arm I Patients receive neoadjuvant chemotherapy and undergo chemoradiotherapy as in phase I
Arm II Patients receive neoadjuvant chemotherapy and undergo chemoradiotherapy as in phase I Patients also receive concurrent lapatinib ditosylate as in phase I at the recommended dose determined in phase I
In both phases treatment continues in the absence of disease progression or unacceptable toxicity
Patients with node-positive disease initially undergo tumor and blood sample collection for biological studies Samples are analyzed for ErbB-related activation via immunohistochemistry in situ hybridization and PCRsequencing of genesproteins to detect DNA amplification and polysomy for AKT ErbB2 EGFR and genomic losses for PTEN via FISH and the ratio between EGFR and EGFRvIII via QRT-PCR Patients with node-positive disease undergo at least elective neck dissection to evaluate the negative predictive value of PET scanning
Patients are followed every 3 months for one year and then every 6 months thereafter
Primary
Determine the maximum tolerated dose and recommended dose for phase II of lapatinib ditosylate in patients with locally advanced squamous cell carcinoma of the larynyx or hypopharynx who are concomitantly treated with neoadjuvant induction chemotherapy comprising docetaxel cisplatin and fluorouracil followed by chemoradiotherapy comprising carboplatin and radiotherapy Phase I
To document the feasibility in the framework of an organ preservation program of this regimen in these patients Phase II
Secondary
To look at the role of PET in patients with N1-3 disease in terms of PET being used as a reliable method to spare patients from planned neck dissection Phase II
OUTLINE This is a multicenter dose-escalation phase I study followed by a randomized phase II study Patients are stratified by institution and EGFR status negative vs positive
Phase I
Neoadjuvant chemotherapy Patients receive neoadjuvant chemotherapy comprising docetaxel IV and cisplatin IV on day 1 and fluorouracil IV continuously on days 1-5 Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity Patients with a complete or partial response after 4 courses of neoadjuvant chemotherapy proceed to chemoradiotherapy Patients with less than a partial response after course 2 or course 4 proceed to surgery including total laryngectomy
Chemoradiotherapy Within 3 weeks after completion of neoadjuvant chemotherapy patients undergo radiotherapy on days 1-5 8-12 15-19 22-26 29-33 36-40 and 43-47 and receive carboplatin IV on days 1 8 15 22 29 36 and 43
Concurrent lapatinib ditosylate Patients receive oral lapatinib ditosylate once daily during neoadjuvant chemotherapy during the break between neoadjuvant chemotherapy and chemoradiotherapy and during chemoradiotherapy
Phase II Patients are randomized to 1 of 2 treatment arms
Arm I Patients receive neoadjuvant chemotherapy and undergo chemoradiotherapy as in phase I
Arm II Patients receive neoadjuvant chemotherapy and undergo chemoradiotherapy as in phase I Patients also receive concurrent lapatinib ditosylate as in phase I at the recommended dose determined in phase I
In both phases treatment continues in the absence of disease progression or unacceptable toxicity
Patients with node-positive disease initially undergo tumor and blood sample collection for biological studies Samples are analyzed for ErbB-related activation via immunohistochemistry in situ hybridization and PCRsequencing of genesproteins to detect DNA amplification and polysomy for AKT ErbB2 EGFR and genomic losses for PTEN via FISH and the ratio between EGFR and EGFRvIII via QRT-PCR Patients with node-positive disease undergo at least elective neck dissection to evaluate the negative predictive value of PET scanning
Patients are followed every 3 months for one year and then every 6 months thereafter
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 |
|---|---|---|---|
| GSK-EORTC-24051 | EudraCT Number | None | None |
| 2006-002667-33 | EUDRACT_NUMBER | None | None |