A Randomized, placebo controlled study to determine the effect of two dose schedules of R1507 or placebo, both in combination with erlotinib (Tarceva®), on progression-free survival in patients with advanced non-small cell lung cancer with disease progression after first or second line chemotherapy.

• Register: EUCTR
• Last refreshed on: 11 August 2014
• Main ID: EUCTR2008-001736-12-BE
• Date of registration: 30/07/2008
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Randomized, placebo controlled study to determine the effect of two dose schedules of R1507 or placebo, both in combination with erlotinib (Tarceva®), on progression-free survival in patients with advanced non-small cell lung cancer with disease progression after first or second line chemotherapy.
• Scientific title: A Randomized, placebo controlled study to determine the effect of two dose schedules of R1507 or placebo, both in combination with erlotinib (Tarceva®), on progression-free survival in patients with advanced non-small cell lung cancer with disease progression after first or second line chemotherapy.
• Date of first enrolment: 12/11/2008
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-001736-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, France, Germany, Ireland, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female patients, age =18 years
2. Able to comply with the protocol
3. Patients must be able to take oral medication
4. Histologically documented inoperable, locally advanced or metastatic (stage IIIB and stage IV) NSCLC. (NOTE: Sputum cytology alone is not acceptable). Tumors with mixed histology should be categorized according to the predominant cell type
5. Prior Treatment: Failed at least one, but no more than two standard chemotherapy regimens
6. Patients who have received maintenance chemotherapy between initial course of therapy (first line) and study entry may enter on the study provided they have not been treated with an agent that targets EGFR or IGF-1R
7. Formalin fixed paraffin embedded tumor tissue samples from initial or subsequent diagnosis representative of the disease must be available for shipment to Roche prior to randomization
8. Measurable disease according to RECIST
9. ECOG performance status 0-2
10. Life expectancy > 12 weeks
11. Adequate hematological function : ANC =1.5 x 10 to the power 9/L;platelets = 100 x 10to the power 9/L, Hb =9 g/dL
12. INR =1.5 and PTT =1.5 x ULN unless receiving anticoagulant therapy
13. Adequate liver function: Serum bilirubin =1.5 x ULN; transaminases =2.5 x ULN (in case of liver metastases <5 x ULN)
14. Adequate renal function: Serum creatinine = 1.5 X ULN
15. Serum calcium = 1.1 X ULN
16. HbA1c = 7%
17. Negative pregnancy test within 7 days of starting study treatment in pre-menopausal women and women < 2 years after the onset of menopause
18. Signed informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Patients must have had a head CT/MRI to evaluate for CNS metastasis within 28 days prior to enrollment. Patients with active CNS lesions are excluded. Patients with
radiographically stable, asymptomatic previously irradiated lesions are eligible provided patients is = 4 weeks beyond completing cranial irradiation and = 3 weeks off corticosteroid therapy
2. Prior treatment with an investigational or commercial agent that acts via IGF-1R inhibition
3. Prior treatment with an agent that acts via EGFR targeting
4. Administration of any anti-cancer therapies other than those administered in this study during protocol treatment
5. Administration of high doses of systemic corticosteroids. High dose is considered more than 1 mg/kg per day of prednisone (or equivalent) for more than 7 consecutive
days. Dexamethasone may induce CYP3A4 activity. CYP3A4 inhibitors and inducers may influence the plasma level of erlotinib
6. Prior irradiation: 1) Radiotherapy given within the last 4 weeks prior to first dose of study treatment. 2) Palliative radiotherapy for bone lesions outside the thoracic region within 2 weeks prior to the first dose of study treatment
7. Prior Surgery: Major Surgery (including open biopsy) or significant traumatic injury within the last 2 weeks prior to first dose of study treatment or anticipation of the need for major surgery during study treatment.
• Patients who undergo minor surgical procedures (for example, placement of a central venous access device) must be sufficiently recovered from the procedure to receive chemotherapy but do not require a mandatory 14 day interval between the procedure and initiation of study treatment.
8. Patients who have not recovered from adverse events to = grade 1, (excluding alopecia) from previously administered therapies and must be randomly assigned to study treatment at least 21 days after chemotherapy (14 days after treatment with vinca alkaloids or gemcitabine)
9. Lactating women
10. Fertile men and women of childbearing potential not using effective methods to prevent pregnancy throughout the trial and for 90 days after last study drug administration in both sexes. Women of childbearing potential must have a negative pregnancy test (serum ß- HCG) within the 7 days prior to study drug administration.
- NOTE: Women of childbearing potential includes both pre-menopausal women and women within the first 2 years of the onset of menopause
- NOTE: Effective methods of birth control includes: surgically sterile, barrier device (condom, diaphragm), contraceptive coil, abstinence. Oral contraceptive pills (OCPs) alone are not considered an effective method
11. Other active cancer requiring treatment
12. Known hypersensitivity to any of the study drugs or their excipients
13. Any disease (including psychotic disorders, drug abuse, active infection, uncontrolled hypertension, clinically significant cardiovascular disease for example CVA (= 6 months before randomization), myocardial infarction (= 6 months before randomization), unstable angina, NYHA = grade 2 CHF, arrhythmia requiring medication, hepatic, renal or metabolic disease (including uncontrolled diabetes mellitus), metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment related complications
14. History of allogeneic bone marrow transplantation or organ

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

To investigate in a randomized fashion if the addition of targeted IGF-1R blockade with R1507 has additional clinical benefit when combined with erlotinib in patients with advanced NSCLC who have failed at least one, but no more than two standard chemotherapy regimens. The study will also investigate 2 doses and schedules of R1507 combined with erlotinib compared with erlotinib and placebo, and assess the safety and tolerability of the combination in this patient population.
MedDRA version: 9.1 Level: LLT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB
MedDRA version: 9.1 Level: LLT Classification code 10029522 Term: Non-small cell lung cancer stage IV

Intervention(s)

Product Name: huMAb IGF-1R
Product Code: RO4858696
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: not yet defined
Current Sponsor code: RO4858696 other code R1507
Other descriptive name: huMAb IGF-1R
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Intravenous infusion
Route of administration of the placebo: Intravenous use

Trade Name: Tarceva (Erlotinib)
Product Name: Tarceva
Product Code: N/A
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tarceva (Erlotinib)
CAS Number: 183321-74-6
Current Sponsor code: 50-8231/ V03
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Tarceva (Erlotinib)
Product Name: Tarceva
Product Code: N/A
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tarceva (Erlotinib)
CAS Number: 183321-74-6
Current Sponsor code: 50-8231/V05
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Secondary Objective: -Secondary:
- Define the effect of adding R1507 to erlotinib on progression-free survival, overall survival, objective response rate, time to response, time to progressive disease and
duration of response.
- Define population PK of R1507 in combination with erlotinib.
- Evaluate the safety profile of the combination of R1507 and erlotinib.
- Explore the changes in pharmacodynamic markers in responders and non-responders.
- Explore candidate biomarkers related to drug mechanism of action.
To explore two doses and schedules of R1507 combined with erlotinib in this setting.

Primary end point(s): Progression-free survival (PFS) at 12 weeks is the primary end-point. PFS is defined as the time from date of randomization to first date of documented disease progression or death.

Main Objective: Primary:
The primary objective is to define the proportion of patients with PFS at 12 weeks with the combination of R1507 and erlotinib or a corresponding placebo and erlotinib in patients with advanced Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC) who have failed at least one standard chemotherapy regimen.

Secondary ID(s)

NO21160