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Docetaxel, Cisplatin, and Erlotinib Hydrochloride in Treating Patients With Stage I-III Non-small Cell Lung Cancer Following Surgery

Primary Purpose

Recurrent Lung Non-Small Cell Carcinoma, Stage IA Lung Non-Small Cell Carcinoma AJCC v7, Stage IB Lung Non-Small Cell Carcinoma AJCC v7

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cisplatin
Docetaxel
Erlotinib
Erlotinib Hydrochloride
Laboratory Biomarker Analysis
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Lung Non-Small Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients must have histologically or cytologically confirmed diagnosis of stage I, II or III non-small cell lung cancer; tissue blocks or slides will be requested Patients must have surgically resectable disease and may not be treated with prior chemotherapy or radiation Patients must be able to tolerate systemic chemotherapy prior to surgical resection No acute intercurrent illness or infection Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Leukocytes >= 3,000/uL Absolute neutrophil count (ANC) >= 1,500/uL Platelets >= 100,000/uL Hemoglobin >= 8g/dL Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Bilirubin within normal institutional limits Alkaline phosphatase (alk phos) =< 2.5 x upper limit of normal (ULN); if alk phos > 2.5 x ULN but =< 5 x ULN, patient is eligible if AST or ALT =< ULN Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 1.5 x ULN; if AST or ALT > 1.5 x ULN but =< 5 x ULN, patient is eligible if alk phos is =< ULN Prior to study enrollment, all women of child-bearing potential must have a negative pregnancy test; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 2 months after the completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Patients with a history of non-melanoma skin cancer, or other malignancies treated 5 years or more prior to the current tumor, from which the patient has remained continually disease-free, are eligible Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients who have had prior chemotherapy or radiotherapy for lung cancer Patients may not be receiving any other investigational agents within 30 days of trial entry, including anti-EGFR drugs Patient has signs or symptoms of acute infection requiring systemic therapy Patient exhibits confusion, disorientation, or has a history of major psychiatric illness that may impair patient's understanding of the informed consent Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Functional Classification class II or worse), unstable angina pectoris, serious or clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patients refusing to sign the informed consent Patients with pre-existing peripheral neuropathy National Cancer Institute (NCI) Common Toxicity Criteria (CTC) grade 2 or worse Patients must not be pregnant or breast-feeding and all (male and female) must use a contraceptive method deemed acceptable by the investigator while receiving active treatment in the study and for up to two months following completion of therapy Patients with a history of severe hypersensitivity reaction to Taxotere and or polysorbate 80 must be excluded

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (docetaxel, cisplatin, erlotinib hydrochloride)

Arm Description

Patients receive docetaxel IV over 1 hour followed by cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning within 90 days following definitive surgical resection, patients receive erlotinib hydrochloride PO daily for up to 1 year.

Outcomes

Primary Outcome Measures

Rate of grade 3 or greater toxicities (hematologic or non-hematologic)
Changes of EGFR expression (i.e., EGFR modulation) between buccal smears and bronchial tissue
Agreement will be estimated using the kappa coefficient. An important aspect of this trial is to identify changes in expression of potential biomarkers between buccal smears and bronchial tissues after induction (neoadjuvant) platinum-based therapy in early-stage , resectable non-small cell lung cancers. As part of the primary outcome measures, we plan to measure the EGFR expression changes (i.e. EGFR modulation) between buccal smears and bronchial tissues after induction therapy.

Secondary Outcome Measures

Incidence of EGFR mutations
The frequency of EGFR mutations in resected tumor specimens following neoadjuvant platinum-based therapy will be evaluated.
Evaluation of immune-based biomarkers
The correlation among various continuous and discrete biomarkers will be assessed first by exploratory data analysis using scatter plot matrix, bx plots, BLiP plot, and trellis plots. Correlation among continuous biomarkers will be estimated by Pearson or Spearman rank correlation coefficient. The association on discrete biomarkers will be tested by chi-square or Fisher's exact test. McNamar's test will be applied to test the change of a single discrete biomarker over time.
Time to progression
Estimated by Kaplan-Meier method. The Cox (proportional hazards) model will be fitted to estimate the effect of biomarker and other covariates on survival.

Full Information

First Posted
November 14, 2005
Last Updated
October 11, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00254384
Brief Title
Docetaxel, Cisplatin, and Erlotinib Hydrochloride in Treating Patients With Stage I-III Non-small Cell Lung Cancer Following Surgery
Official Title
Neoadjuvant Chemotherapy With Docetaxel, Cisplatin Followed by Maintenance Therapy With the EGFR Inhibitor Erlotinib (Tarceva) in Patients With Stage I, II and III Non-Small Cell Lung Cancer Following Definitive Surgical Resection
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 5, 2005 (Actual)
Primary Completion Date
October 31, 2025 (Anticipated)
Study Completion Date
October 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase I trial studies docetaxel, cisplatin, and erlotinib hydrochloride in treating patients with stage I-III non-small cell lung cancer following surgery. Drugs used in chemotherapy, such as docetaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving docetaxel, cisplatin, and erlotinib hydrochloride together may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the safety/toxicity of neoadjuvant chemotherapy with cisplatin and docetaxel followed by maintenance therapy with the epidermal growth factor receptor (EGFR) inhibitor erlotinib (erlotinib hydrochloride) in patients with stage I-III non-small cell lung cancer (NSCLC) undergoing definitive treatment with surgery and/or radiation. II. To estimate the agreement in baseline to post-treatment changes of EGFR expression (i.e., EGFR modulation) between buccal smears and bronchial tissue. SECONDARY OBJECTIVES: I. To evaluate the disease free survival of this therapeutic combination. II. To assess overall quality of life. III. To evaluate predictive biomarkers in early-stage NSCLC. OUTLINE: Patients receive docetaxel intravenously (IV) over 1 hour followed by cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning within 90 days following definitive surgical resection, patients receive erlotinib hydrochloride orally (PO) daily for up to 1 year. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 4 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Lung Non-Small Cell Carcinoma, Stage IA Lung Non-Small Cell Carcinoma AJCC v7, Stage IB Lung Non-Small Cell Carcinoma AJCC v7, Stage IIA Lung Non-Small Cell Carcinoma AJCC v7, Stage IIB Lung Non-Small Cell Carcinoma AJCC v7, Stage IIIA Lung Non-Small Cell Cancer AJCC v7, Stage IIIB Lung Non-Small Cell Cancer AJCC v7

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (docetaxel, cisplatin, erlotinib hydrochloride)
Arm Type
Experimental
Arm Description
Patients receive docetaxel IV over 1 hour followed by cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning within 90 days following definitive surgical resection, patients receive erlotinib hydrochloride PO daily for up to 1 year.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone''s Chloride, Peyrone''s Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
Docecad, RP56976, Taxotere, Taxotere Injection Concentrate
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Erlotinib Hydrochloride
Other Intervention Name(s)
Cp-358,774, OSI-774, Tarceva
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Rate of grade 3 or greater toxicities (hematologic or non-hematologic)
Time Frame
Up to 5 years post-treatment
Title
Changes of EGFR expression (i.e., EGFR modulation) between buccal smears and bronchial tissue
Description
Agreement will be estimated using the kappa coefficient. An important aspect of this trial is to identify changes in expression of potential biomarkers between buccal smears and bronchial tissues after induction (neoadjuvant) platinum-based therapy in early-stage , resectable non-small cell lung cancers. As part of the primary outcome measures, we plan to measure the EGFR expression changes (i.e. EGFR modulation) between buccal smears and bronchial tissues after induction therapy.
Time Frame
From baseline up to 5 years post-treatment
Secondary Outcome Measure Information:
Title
Incidence of EGFR mutations
Description
The frequency of EGFR mutations in resected tumor specimens following neoadjuvant platinum-based therapy will be evaluated.
Time Frame
Up to 5 years post-treatment
Title
Evaluation of immune-based biomarkers
Description
The correlation among various continuous and discrete biomarkers will be assessed first by exploratory data analysis using scatter plot matrix, bx plots, BLiP plot, and trellis plots. Correlation among continuous biomarkers will be estimated by Pearson or Spearman rank correlation coefficient. The association on discrete biomarkers will be tested by chi-square or Fisher's exact test. McNamar's test will be applied to test the change of a single discrete biomarker over time.
Time Frame
Up to 5 years post-treatment
Title
Time to progression
Description
Estimated by Kaplan-Meier method. The Cox (proportional hazards) model will be fitted to estimate the effect of biomarker and other covariates on survival.
Time Frame
Up to 5 years post-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically or cytologically confirmed diagnosis of stage I, II or III non-small cell lung cancer; tissue blocks or slides will be requested Patients must have surgically resectable disease and may not be treated with prior chemotherapy or radiation Patients must be able to tolerate systemic chemotherapy prior to surgical resection No acute intercurrent illness or infection Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Leukocytes >= 3,000/uL Absolute neutrophil count (ANC) >= 1,500/uL Platelets >= 100,000/uL Hemoglobin >= 8g/dL Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Bilirubin within normal institutional limits Alkaline phosphatase (alk phos) =< 2.5 x upper limit of normal (ULN); if alk phos > 2.5 x ULN but =< 5 x ULN, patient is eligible if AST or ALT =< ULN Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 1.5 x ULN; if AST or ALT > 1.5 x ULN but =< 5 x ULN, patient is eligible if alk phos is =< ULN Prior to study enrollment, all women of child-bearing potential must have a negative pregnancy test; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 2 months after the completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Patients with a history of non-melanoma skin cancer, or other malignancies treated 5 years or more prior to the current tumor, from which the patient has remained continually disease-free, are eligible Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients who have had prior chemotherapy or radiotherapy for lung cancer Patients may not be receiving any other investigational agents within 30 days of trial entry, including anti-EGFR drugs Patient has signs or symptoms of acute infection requiring systemic therapy Patient exhibits confusion, disorientation, or has a history of major psychiatric illness that may impair patient's understanding of the informed consent Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Functional Classification class II or worse), unstable angina pectoris, serious or clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patients refusing to sign the informed consent Patients with pre-existing peripheral neuropathy National Cancer Institute (NCI) Common Toxicity Criteria (CTC) grade 2 or worse Patients must not be pregnant or breast-feeding and all (male and female) must use a contraceptive method deemed acceptable by the investigator while receiving active treatment in the study and for up to two months following completion of therapy Patients with a history of severe hypersensitivity reaction to Taxotere and or polysorbate 80 must be excluded
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tina Cascone, MD,PHD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29217088
Citation
Cascone T, Gold KA, Swisher SG, Liu DD, Fossella FV, Sepesi B, Pataer A, Weissferdt A, Kalhor N, Vaporciyan AA, Hofstetter WL, Wistuba II, Heymach JV, Kim ES, William WN Jr. Induction Cisplatin Docetaxel Followed by Surgery and Erlotinib in Non-Small Cell Lung Cancer. Ann Thorac Surg. 2018 Feb;105(2):418-424. doi: 10.1016/j.athoracsur.2017.08.052. Epub 2017 Dec 6.
Results Reference
derived
Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center

Learn more about this trial

Docetaxel, Cisplatin, and Erlotinib Hydrochloride in Treating Patients With Stage I-III Non-small Cell Lung Cancer Following Surgery

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