Back to resultsA Study of the Effect of R1507 in Combination With Tarceva (Erlotinib) on Progression-Free Survival in Patients With Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC) Having Received Tarceva Monotherapy.
Primary Purpose
Non-Small Cell Lung Cancer
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
RG1507
erlotinib [Tarceva]
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
- male or female patients >=18 years with histologically documented inoperable, locally advanced or metastatic (stage IIIB or IV) NSCLC;
- currently receiving Tarceva monotherapy and having failed at least one standard chemotherapy regimens;
- prior response or stable disease 12 weeks from start of Tarceva;
- documented progressive disease at enrollment;
- measurable disease according to the RECIST criteria;
- ECOG performance status 0-2;
- life expectancy >12 weeks.
Exclusion Criteria:
- patients with active CNS lesions;
- prior treatment with agents acting via IGF-1R inhibition or EGFR targeting;
- administration with high doses of systemic corticosteroids;
- radiotherapy in the 4 weeks prior to study start;
- surgery or significant traumatic injury with in the last 2 weeks prior to study start.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Participants With Progression Free Survival (PFS)
The primary efficacy endpoint is progression-free survival at 12 weeks after start of therapy. A progression-free survival rate at 12 weeks will be calculated, with patients categorized in a dichotomous manner as alive and progression-free or in progression or dead at 12 weeks.
Secondary Outcome Measures
Duration of Overall Survival
The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Participants Achieving Objective Response
Objective response is defined as a complete response (CR) or partial response (PR) that has been confirmed by a second tumor assessment no earlier than 4 weeks after the initial documentation. Response is assessed using Response Evaluation Criteria in Solid Tumors (RECIST)criteria.
The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time to Best Response
This is defined as time from the start of therapy to the date of first CR or PR.
The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time to Progressive Disease (PD)
The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Duration of Objective Response
This is defined similarly for complete and partial responders. Complete response or partial response lasts from the date the complete response or partial response was first recorded to the date on which progressive disease is first noted or date of death. If a patient does not progress or die while being followed, the date of the last valid tumor assessment will be taken. The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Baseline Electrocardiogram (ECG)
Standard safety monitoring includes baseline Electrocardiogram (ECG).
The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed. The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Fasting Glucose, Highest Post-Baseline Value
A fasting glucose was required at baseline, and random non-fasting glucose testing was performed weekly for the first 6 weeks followed by day 1 of each 3 week treatment phase. The number of participants with the highest post-baseline fasting glucose level at any time point post baseline relative to the participant's baseline glucose level is reported.
Hemoglobin A1c (HbA1c)
Standard safety monitoring includes baseline Electrocardiogram (ECG), Fasting glucose and HbA1c, monthly urine pregnancy test in female patients of childbearing potential and Human anti-human antibody (HAHA) testing.
Data will be represented in the Serious Adverse Event (SAE) Adverse Event (AE) section of Protocol Registration System (PRS).
Monthly Urine Pregnancy Test in Female Patients of Childbearing Potential
Standard safety monitoring includes baseline Electrocardiogram (ECG), Fasting glucose and HbA1c, monthly urine pregnancy test in female patients of childbearing potential and Human anti-human antibody (HAHA) testing.
Not posted; it will be represented in the Serious Adverse Event (SAE) Adverse Event (AE) section of Protocol Registration System (PRS).
Number of Participants With Positive Results for Human Anti-human Antibody (HAHA) Testing
Number of participants who tested positive for Human anti-human antibody (HAHA) testing for immunogenicity.
To determine HAHA specificity, screened positive samples were tested in a confirmatory assay in the presence of 10 ug/mL R1507. Samples with > 19.7% inhibition were considered true positives, whereas those with < 19.7% inhibition were considered to be false positives.
Electrocardiogram (ECG)
12 lead ECG is required at baseline and will be measured during the trial as clinically indicated at the discretion of the investigators. For each reading, QTcF value will be calculated as the QT value (seconds) divided by the cube root of the RR interval in seconds (Fridericia correction). A listing will be generated showing, for each patient, the visits at which ECGs were taken and the results (normal or abnormal, as well as any comments provided).
Population Pharmacokinetics of R1507 and Tarceva
Population PK of R1507 and erlotinib were planned but not analyzed due to the termination of the trial.
Assessment of Potential Predictive and Prognostic Biomarkers.
Total IGF-I, free IGF I/II and other potential biomarkers present in serum. Further putative biomarker analyses in blood and tumor samples were planned in the protocol for exploratory assessment of correlation with clinical outcome. None of these were analyzed due to the termination of the trial.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00773383
Brief Title
A Study of the Effect of R1507 in Combination With Tarceva (Erlotinib) on Progression-Free Survival in Patients With Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC) Having Received Tarceva Monotherapy.
Official Title
An Open-label Study to Determine the Effect of R1507 Plus Tarceva (Erlotinib) on Progression-free Survival in Patients With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) With Progressive Disease After Clinical Benefit to Second or Third Line Tarceva Monotherapy.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2013
Overall Recruitment Status
Terminated
Study Start Date
November 2008 (undefined)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
February 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
This single arm study in patients with advanced Stage IIIb/IV NSCLC who have progressive disease after deriving clinical benefit (defined as response or stable disease after 12 weeks) from second or third line Tarceva monotherapy will determine the proportion of patients with progression-free survival at 12 weeks following combination therapy with R1507 and Tarceva. Patients will receive R1507 (9mg/kg iv) weekly in combination with Tarceva (150mg oral daily) for up to a maximum of 24 months. Other disease-related endpoints including overall survival, objective response rate, time to response, time to progressive disease and duration of response will also be evaluated. The anticipated time on study treatment is 1-2 years, and the target sample size is <100 individuals.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
RG1507
Intervention Description
iv 9mg/kg weekly
Intervention Type
Drug
Intervention Name(s)
erlotinib [Tarceva]
Intervention Description
150mg oral daily
Primary Outcome Measure Information:
Title
Percentage of Participants With Progression Free Survival (PFS)
Description
The primary efficacy endpoint is progression-free survival at 12 weeks after start of therapy. A progression-free survival rate at 12 weeks will be calculated, with patients categorized in a dichotomous manner as alive and progression-free or in progression or dead at 12 weeks.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Duration of Overall Survival
Description
The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time Frame
From start of treatment to death; up to the time that all participants ended treatment
Title
Participants Achieving Objective Response
Description
Objective response is defined as a complete response (CR) or partial response (PR) that has been confirmed by a second tumor assessment no earlier than 4 weeks after the initial documentation. Response is assessed using Response Evaluation Criteria in Solid Tumors (RECIST)criteria.
The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time Frame
Patients were followed from start of therapy until date of first response
Title
Time to Best Response
Description
This is defined as time from the start of therapy to the date of first CR or PR.
The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time Frame
Patients were followed from start of therapy until date of first response
Title
Time to Progressive Disease (PD)
Description
The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time Frame
From start of therapy to the date of first documentation of PD. Pts who never progress prior to final analysis or are withdrawn from the study without documented progression will be censored at the date of the last valid tumor assessment.
Title
Duration of Objective Response
Description
This is defined similarly for complete and partial responders. Complete response or partial response lasts from the date the complete response or partial response was first recorded to the date on which progressive disease is first noted or date of death. If a patient does not progress or die while being followed, the date of the last valid tumor assessment will be taken. The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time Frame
from the date the complete or partial response was first recorded to the date which progressive disease is first noted or date of death. If a patient does not progress or die while being followed, the date of the last valid tumor assessment will be taken
Title
Baseline Electrocardiogram (ECG)
Description
Standard safety monitoring includes baseline Electrocardiogram (ECG).
The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed. The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time Frame
baseline within 28 days of starting treatment (screening visit).
Title
Fasting Glucose, Highest Post-Baseline Value
Description
A fasting glucose was required at baseline, and random non-fasting glucose testing was performed weekly for the first 6 weeks followed by day 1 of each 3 week treatment phase. The number of participants with the highest post-baseline fasting glucose level at any time point post baseline relative to the participant's baseline glucose level is reported.
Time Frame
Baseline, Highest Post-Baseline value within the timeframe of post-baseline collection up to when patient discontinued (up to 59 weeks)
Title
Hemoglobin A1c (HbA1c)
Description
Standard safety monitoring includes baseline Electrocardiogram (ECG), Fasting glucose and HbA1c, monthly urine pregnancy test in female patients of childbearing potential and Human anti-human antibody (HAHA) testing.
Data will be represented in the Serious Adverse Event (SAE) Adverse Event (AE) section of Protocol Registration System (PRS).
Time Frame
screening
Title
Monthly Urine Pregnancy Test in Female Patients of Childbearing Potential
Description
Standard safety monitoring includes baseline Electrocardiogram (ECG), Fasting glucose and HbA1c, monthly urine pregnancy test in female patients of childbearing potential and Human anti-human antibody (HAHA) testing.
Not posted; it will be represented in the Serious Adverse Event (SAE) Adverse Event (AE) section of Protocol Registration System (PRS).
Time Frame
Within 7 days of starting treatment (baseline visit)
Title
Number of Participants With Positive Results for Human Anti-human Antibody (HAHA) Testing
Description
Number of participants who tested positive for Human anti-human antibody (HAHA) testing for immunogenicity.
To determine HAHA specificity, screened positive samples were tested in a confirmatory assay in the presence of 10 ug/mL R1507. Samples with > 19.7% inhibition were considered true positives, whereas those with < 19.7% inhibition were considered to be false positives.
Time Frame
prior to dosing on week 1 (day 1), week 4 (day 22), week 10 (day 64), final visit, follow up visit and 12 weeks post last dose (up to 71 weeks)
Title
Electrocardiogram (ECG)
Description
12 lead ECG is required at baseline and will be measured during the trial as clinically indicated at the discretion of the investigators. For each reading, QTcF value will be calculated as the QT value (seconds) divided by the cube root of the RR interval in seconds (Fridericia correction). A listing will be generated showing, for each patient, the visits at which ECGs were taken and the results (normal or abnormal, as well as any comments provided).
Time Frame
baseline and thereafter as clinically indicated at the discretion of the investigator up to the time that the patient discontinued (up to 59 weeks)
Title
Population Pharmacokinetics of R1507 and Tarceva
Description
Population PK of R1507 and erlotinib were planned but not analyzed due to the termination of the trial.
Time Frame
Throughout study
Title
Assessment of Potential Predictive and Prognostic Biomarkers.
Description
Total IGF-I, free IGF I/II and other potential biomarkers present in serum. Further putative biomarker analyses in blood and tumor samples were planned in the protocol for exploratory assessment of correlation with clinical outcome. None of these were analyzed due to the termination of the trial.
Time Frame
Throughout study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
male or female patients >=18 years with histologically documented inoperable, locally advanced or metastatic (stage IIIB or IV) NSCLC;
currently receiving Tarceva monotherapy and having failed at least one standard chemotherapy regimens;
prior response or stable disease 12 weeks from start of Tarceva;
documented progressive disease at enrollment;
measurable disease according to the RECIST criteria;
ECOG performance status 0-2;
life expectancy >12 weeks.
Exclusion Criteria:
patients with active CNS lesions;
prior treatment with agents acting via IGF-1R inhibition or EGFR targeting;
administration with high doses of systemic corticosteroids;
radiotherapy in the 4 weeks prior to study start;
surgery or significant traumatic injury with in the last 2 weeks prior to study start.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33101
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
City
Hickory
State/Province
North Carolina
ZIP/Postal Code
28602
Country
United States
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3G 1A4
Country
Canada
City
Marseille
ZIP/Postal Code
13015
Country
France
City
Paris
ZIP/Postal Code
75230
Country
France
City
Villejuif
ZIP/Postal Code
94805
Country
France
City
Gdansk
ZIP/Postal Code
80-211
Country
Poland
City
Lublin
ZIP/Postal Code
20-950
Country
Poland
City
Poznan
ZIP/Postal Code
60-569
Country
Poland
12. IPD Sharing Statement
Learn more about this trial
A Study of the Effect of R1507 in Combination With Tarceva (Erlotinib) on Progression-Free Survival in Patients With Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC) Having Received Tarceva Monotherapy.
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