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A Study Comparing Sequential Satraplatin & Erlotinib to Erlotinib in Unresectable Stage 3/4 Non-small-cell Lung Cancer (NSCLC)

Primary Purpose

Lung Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Erlotinib
Satraplatin
Sponsored by
Agennix
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring Non Small Cell Lung Cancer, PATIENTS ≥ 70 YEARS WITH UNRESECTABLE STAGE 3 OR 4 NSCLC

Eligibility Criteria

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

Inclusion Criteria: Histologically or cytologically confirmed NSCLC (squamous cell carcinoma, adenocarcinoma, or large cell carcinoma). Cytologic specimens obtained by brushings, washings or needle biopsy with aspiration are acceptable. Mixed tumors with small cell anaplastic elements are not eligible. Patients who have unresectable stage III or stage IV disease are eligible. Patients with stage III disease should be ineligible for combined modality therapy (i.e. pleural effusions, pericardial effusions, etc.). Patients with earlier stage NSCLC that has recurred after prior surgery are eligible. Age ≥ 70 years old. ECOG performance status 0-1 Prior treatment with systemic therapy is allowed provided the following criteria are met: No EGFR targeted therapy (TKI or antibody) No prior platinum agent. Neoadjuvant, adjuvant, or part of a combined modality regimen (i.e., not for metastatic disease) Completion > 6 months prior to enrollment onto this study. Patients who have had previous radiation therapy (RT) as definitive therapy for locally NSCLC are eligible only if the following criteria are met: Site of tumor recurrence is outside of the original RT port unless there is incontrovertible evidence of disease progression within the portal All side effects from RT must have resolved prior to enrollment. Completion of RT ≥ 4 weeks prior to enrollment. Previous radiation must have treated < 30% of active bone marrow. Patients who have undergone thoracotomy must have fully recovered from surgery and cannot start treatment until at least three weeks after their operative procedure. Adequate hematological function as noted by: Absolute neutrophil count (ANC) > 1,500/ L Platelets > 100,000/ L Hemoglobin > 10 g/dl. Patients may be transfused or receive erythropoietin to maintain or exceed this level. Adequate hepatic and renal function as noted by: Bilirubin < 1.5 x ULN Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) < 2.5 x ULN. Serum creatinine ≤ 1.5mg/dL or calculated (or measured) glomerular filtration rate ≥ (GFR)50 ml/min. Patients with both measurable and non-measurable disease (as per Response Criteria in Solid Tumors (RECIST)) may be enrolled. Exclusion Criteria: Concurrent invasive malignancy requiring ongoing therapy. Metastatic brain or meningeal tumors, unless the patient is > 1 month from definitive therapy, is clinically stable with respect to the tumor at the time of study entry, is not receiving steroid therapy or taper, and is not receiving anti-convulsant medications (that were started for the brain metastases). Previous treatment with either platinum-based chemotherapy agents or prior EGFR targeting agents. Peripheral neuropathy > grade 1. Hearing loss or tinnitus > grade 2 Obstructive pulmonary disease or symptoms > grade 3. A history of cardiac disease as defined by malignant hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous six months, or symptomatic uncontrolled cardiac arrhythmias.

Sites / Locations

  • Pacific Cancer Medical Center
  • Scripps Clinic
  • Kenmar Research Institute
  • Memorial Cancer Institute
  • University of Miami Sylvester Cancer Center
  • Rush University Medical Center
  • Highlands Oncology Group
  • Gabrail Cancer Center
  • Cleveland Clinic Foundation
  • Signal Point Hematology/Oncology
  • Fox Chase Cancer Center
  • McGill University
  • Princess Margaret Hospital
  • Hospital San Borja Arriaran
  • Instituto Nacional del Cancer
  • Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Satraplatin

Erlotinib

Arm Description

Satraplatin administered orally once daily for 5 consecutive days followed by erlotinib for 14 consecutive days

Erlotinib administered orally once daily. Erlotinib - [6,7-Bis(2-methoxy-ethoxy)-quinazolin-4-y]- (3-ethynyl-phenyl)amine hydrochloride, molecular weight 393.4. This is a small molecule that competes with the binding of ATP to the intracellular tyrosine kinase domain of EGFR, thereby inhibiting receptor autophosphorylation and blocking downstream signal transduction.

Outcomes

Primary Outcome Measures

To compare Progression-Free Survival (PFS) in patients ≥ 70 years of age, PS 0-1, with advanced or metastatic NSCLC in patients treated with a first-line regimen of either sequential satraplatin and erlotinib or continuous single-agent erlotinib.

Secondary Outcome Measures

To assess Overall Survival in patients ≥ 70 years of age, PS 0-1, with advanced or metastatic NSCLC in patients treated with a first-line regimen of either sequential satraplatin and erlotinib or continuous single-agent erlotinib.
To compare response rates.
To compare the toxicity profiles between patients treated with satraplatin and erlotinib and single-agent erlotinib

Full Information

First Posted
August 30, 2006
Last Updated
July 31, 2012
Sponsor
Agennix
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1. Study Identification

Unique Protocol Identification Number
NCT00370383
Brief Title
A Study Comparing Sequential Satraplatin & Erlotinib to Erlotinib in Unresectable Stage 3/4 Non-small-cell Lung Cancer (NSCLC)
Official Title
A Phase 2 Study Comparing Sequential Satraplatin and Erlotinib to Single-Agent Erlotinib in Patients ≥ 70 Years of Age With Unresectable Stage 3 OR 4 Non-Small Cell Lung Cancer as 1st-Line Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
July 2006 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Agennix

4. Oversight

5. Study Description

Brief Summary
Patients ≥ 70 years of age with locally advanced unresectable or metastatic non-small cell lung cancer (NSCLC) frequently do not receive systemic cytotoxic chemotherapy due to concerns regarding their inability to tolerate treatment. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are agents with favorable toxicity profiles that have shown activity in patients with NSCLC. Erlotinib as a single-agent is currently approved for the treatment of patients with NSCLC whose disease has progressed following one prior course of chemotherapy and is currently being evaluated in NSCLC patients who have not received prior systemic treatment. However, when studied with combination chemotherapy in the first-line setting, continuous daily administration of erlotinib did not result in improved patient survival. Further clinical and in vitro data suggest that the sequencing of cytotoxic chemotherapy with EGFR TKIs is important to maximize their therapeutic potential when administered in combination. Satraplatin is an oral, investigational anticancer drug that is a member of the platinum-based class of chemotherapy drugs. Platinum-based drugs have been clinically proven to be one of the most effective classes of anticancer therapies. Unlike the currently marketed platinum-based drugs, satraplatin can be given orally and is currently being evaluated in a pivotal phase 3 clinical trial as 2nd-line therapy for patients with hormone refractory prostate cancer. The rationale for this study is to develop an active and well-tolerated oral regimen for patients ≥ 70 years of age with NSCLC. Administration of the study drugs will be sequenced with satraplatin administered on days 1-5 and erlotinib on days 8-21 of each 28-day cycle. The primary endpoint will be progression-free survival (PFS). Patients will be randomized to treatment with either the experimental regimen or single-agent continuous erlotinib.
Detailed Description
Erlotinib as a single-agent is currently approved for the treatment of patients with NSCLC whose disease has progressed following one prior course of chemotherapy and is currently being evaluated in NSCLC patients who have not received prior systemic treatment. However, when studied with combination chemotherapy in the first-line setting, continuous daily administration of erlotinib did not result in improved patient survival. Further clinical and in vitro data suggest that the sequencing of cytotoxic chemotherapy with EGFR TKIs is important to maximize their therapeutic potential when administered in combination. Satraplatin is an orally administered platinum analogue that has shown promising single-agent activity in multiple tumor types including prostate, ovarian, and small cell lung cancer. Additionally, the single-agent activity of satraplatin in NSCLC is similar to that of other commonly used platinum agents used to treat NSCLC. However, satraplatin is better tolerated than cisplatin, causing less renal toxicity and ototoxicity, and it can be administered in the outpatient setting. From a toxicity profile, it is more similar to carboplatin in that myelosuppression is its dose limiting toxicity (DLT). Satraplatin is currently being evaluated in a pivotal phase 3 clinical trial as 2nd-line therapy for patients with hormone refractory prostate cancer. The rationale for this study is to develop an active and well-tolerated oral regimen for patients ≥ 70 years of age with NSCLC who may not be candidates for aggressive combination systemic chemotherapy. Administration of the study drugs will be sequenced with satraplatin administered on days 1-5 and erlotinib on days 8-21 of each 28-day cycle. As erlotinib has shown an advantage in survival without a commensurate improvement in response rate, the primary endpoint will be progression-free survival (PFS); thus patients will be randomized to treatment with either the experimental regimen or single-agent continuous erlotinib.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
Non Small Cell Lung Cancer, PATIENTS ≥ 70 YEARS WITH UNRESECTABLE STAGE 3 OR 4 NSCLC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Satraplatin
Arm Type
Experimental
Arm Description
Satraplatin administered orally once daily for 5 consecutive days followed by erlotinib for 14 consecutive days
Arm Title
Erlotinib
Arm Type
Experimental
Arm Description
Erlotinib administered orally once daily. Erlotinib - [6,7-Bis(2-methoxy-ethoxy)-quinazolin-4-y]- (3-ethynyl-phenyl)amine hydrochloride, molecular weight 393.4. This is a small molecule that competes with the binding of ATP to the intracellular tyrosine kinase domain of EGFR, thereby inhibiting receptor autophosphorylation and blocking downstream signal transduction.
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Intervention Description
erlotinib 150 mg/day once daily
Intervention Type
Drug
Intervention Name(s)
Satraplatin
Intervention Description
satraplatin 100 mg/m2 orally once daily for 5 consecutive days (days 1-5)followed by erlotinib 150mg/day for 14 consecutive days (days 8-21). Satraplatin JM-216, bis-aceto-ammine dischlorocyclohexylamine platinum)is a third-generation platinum analogue with activity following oral administration. The molecular formula for satraplatin is C10H22N2Cl2O4Pt, which is structured as an octahedral platinum compound.
Primary Outcome Measure Information:
Title
To compare Progression-Free Survival (PFS) in patients ≥ 70 years of age, PS 0-1, with advanced or metastatic NSCLC in patients treated with a first-line regimen of either sequential satraplatin and erlotinib or continuous single-agent erlotinib.
Time Frame
January, 2008
Secondary Outcome Measure Information:
Title
To assess Overall Survival in patients ≥ 70 years of age, PS 0-1, with advanced or metastatic NSCLC in patients treated with a first-line regimen of either sequential satraplatin and erlotinib or continuous single-agent erlotinib.
Time Frame
January, 2008
Title
To compare response rates.
Time Frame
January, 2008
Title
To compare the toxicity profiles between patients treated with satraplatin and erlotinib and single-agent erlotinib
Time Frame
January, 2008

10. Eligibility

Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed NSCLC (squamous cell carcinoma, adenocarcinoma, or large cell carcinoma). Cytologic specimens obtained by brushings, washings or needle biopsy with aspiration are acceptable. Mixed tumors with small cell anaplastic elements are not eligible. Patients who have unresectable stage III or stage IV disease are eligible. Patients with stage III disease should be ineligible for combined modality therapy (i.e. pleural effusions, pericardial effusions, etc.). Patients with earlier stage NSCLC that has recurred after prior surgery are eligible. Age ≥ 70 years old. ECOG performance status 0-1 Prior treatment with systemic therapy is allowed provided the following criteria are met: No EGFR targeted therapy (TKI or antibody) No prior platinum agent. Neoadjuvant, adjuvant, or part of a combined modality regimen (i.e., not for metastatic disease) Completion > 6 months prior to enrollment onto this study. Patients who have had previous radiation therapy (RT) as definitive therapy for locally NSCLC are eligible only if the following criteria are met: Site of tumor recurrence is outside of the original RT port unless there is incontrovertible evidence of disease progression within the portal All side effects from RT must have resolved prior to enrollment. Completion of RT ≥ 4 weeks prior to enrollment. Previous radiation must have treated < 30% of active bone marrow. Patients who have undergone thoracotomy must have fully recovered from surgery and cannot start treatment until at least three weeks after their operative procedure. Adequate hematological function as noted by: Absolute neutrophil count (ANC) > 1,500/ L Platelets > 100,000/ L Hemoglobin > 10 g/dl. Patients may be transfused or receive erythropoietin to maintain or exceed this level. Adequate hepatic and renal function as noted by: Bilirubin < 1.5 x ULN Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) < 2.5 x ULN. Serum creatinine ≤ 1.5mg/dL or calculated (or measured) glomerular filtration rate ≥ (GFR)50 ml/min. Patients with both measurable and non-measurable disease (as per Response Criteria in Solid Tumors (RECIST)) may be enrolled. Exclusion Criteria: Concurrent invasive malignancy requiring ongoing therapy. Metastatic brain or meningeal tumors, unless the patient is > 1 month from definitive therapy, is clinically stable with respect to the tumor at the time of study entry, is not receiving steroid therapy or taper, and is not receiving anti-convulsant medications (that were started for the brain metastases). Previous treatment with either platinum-based chemotherapy agents or prior EGFR targeting agents. Peripheral neuropathy > grade 1. Hearing loss or tinnitus > grade 2 Obstructive pulmonary disease or symptoms > grade 3. A history of cardiac disease as defined by malignant hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous six months, or symptomatic uncontrolled cardiac arrhythmias.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Corey Langer, MD
Organizational Affiliation
Fox Chase Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pacific Cancer Medical Center
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Scripps Clinic
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Kenmar Research Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90057
Country
United States
Facility Name
Memorial Cancer Institute
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
University of Miami Sylvester Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Highlands Oncology Group
City
Bentonville
State/Province
Ohio
ZIP/Postal Code
72712
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Signal Point Hematology/Oncology
City
Middleton
State/Province
Ohio
ZIP/Postal Code
45042
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19110
Country
United States
Facility Name
McGill University
City
Montreal
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
Country
Canada
Facility Name
Hospital San Borja Arriaran
City
Santiago
Country
Chile
Facility Name
Instituto Nacional del Cancer
City
Santiago
Country
Chile
Facility Name
Research Center
City
Santiago
Country
Chile

12. IPD Sharing Statement

Learn more about this trial

A Study Comparing Sequential Satraplatin & Erlotinib to Erlotinib in Unresectable Stage 3/4 Non-small-cell Lung Cancer (NSCLC)

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