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.

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00773383
First received: October 15, 2008
Last updated: June 19, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: RG1507
Drug: erlotinib [Tarceva]
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Progression Free Survival (PFS) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: From start of treatment to death; up to the time that all participants ended treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Patients were followed from start of therapy until date of first response ] [ Designated as safety issue: No ]

    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 [ Time Frame: Patients were followed from start of therapy until date of first response ] [ Designated as safety issue: No ]

    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) [ 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. ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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) [ Time Frame: baseline within 28 days of starting treatment (screening visit). ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline, Highest Post-Baseline value within the timeframe of post-baseline collection up to when patient discontinued (up to 59 weeks) ] [ Designated as safety issue: No ]
    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) [ Time Frame: screening ] [ Designated as safety issue: No ]

    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 [ Time Frame: Within 7 days of starting treatment (baseline visit) ] [ Designated as safety issue: No ]

    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 [ 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) ] [ Designated as safety issue: No ]

    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) [ 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
    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. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
    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.


Enrollment: 35
Study Start Date: November 2008
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: RG1507
iv 9mg/kg weekly
Drug: erlotinib [Tarceva]
150mg oral daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00773383

Locations
United States, California
Santa Monica, California, United States, 90404
United States, Florida
Miami, Florida, United States, 33101
United States, Massachusetts
Boston, Massachusetts, United States, 02115
Boston, Massachusetts, United States, 02114
Boston, Massachusetts, United States, 02215
United States, North Carolina
Hickory, North Carolina, United States, 28602
Canada, Alberta
Calgary, Alberta, Canada, T2N 4N2
Canada, Ontario
Ottawa, Ontario, Canada, K1H 8L6
Canada, Quebec
Montreal, Quebec, Canada, H3A 1A1
Montreal, Quebec, Canada, H3G 1A4
France
Marseille, France, 13015
Paris, France, 75230
Villejuif, France, 94805
Poland
Gdansk, Poland, 80-211
Lublin, Poland, 20-950
Poznan, Poland, 60-569
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00773383     History of Changes
Other Study ID Numbers: NO21746, 2008-001762-85
Study First Received: October 15, 2008
Results First Received: March 31, 2011
Last Updated: June 19, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014