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).

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Terminated

CT.gov ID

NCT00760929

Collaborator

(none)

171

Enrollment

Locations

Arms

19.4

Actual Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This 4 arm study in patients with advanced Stage IIIb/IV non-small cell cancer (NSCLC) who failed at least one standard chemotherapy regimen will determine the proportion of patients with progression-free survival at 12 weeks following combination therapy with R1507 and Tarceva or placebo and Tarceva. Patients will be randomized to one of four treatment arms to receive R1507 (9mg/kg iv) or placebo weekly or R1507 (16mg/kg iv) or placebo every 3 weeks. Tarceva (150mg oral daily) will be administered in all treatment arms. 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 <500 individuals.

Condition or Disease	Intervention/Treatment	Phase
Non-Squamous Non-Small Cell Lung Cancer	Drug: Placebo Drug: Placebo Drug: RG1507 Drug: RG1507 Drug: erlotinib [Tarceva]	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

171 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official 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

Actual Study Start Date :

Nov 10, 2008

Actual Primary Completion Date :

Jun 25, 2010

Actual Study Completion Date :

Jun 25, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo for R1507 (16mg/kg iv)	Drug: Placebo iv 16mg/kg every 3 weeks Drug: erlotinib [Tarceva] 150mg oral daily
Placebo Comparator: Placebo for R1507 (9mg/kg iv)	Drug: Placebo iv 9mg/kg weekly Drug: erlotinib [Tarceva] 150mg oral daily
Experimental: R1507 (16mg/kg iv)	Drug: RG1507 iv 16mg/kg every 3 weeks Drug: erlotinib [Tarceva] 150mg oral daily
Experimental: R1507 (9mg/kg iv)	Drug: RG1507 iv 9mg/kg weekly Drug: erlotinib [Tarceva] 150mg oral daily

Outcome Measures

Primary Outcome Measures

Number of Participants With Progression Free Survival (PFS) [12 weeks]
PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]) based on RECIST tumor response criteria or died from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants who had not died or progressed at the time of the final analysis were censored at the date of last contact.

Secondary Outcome Measures

Overall Survival (OS) [From baseline up to 20 months]
OS was defined as the median time, in weeks, from the date of randomization to the date of death, due to any cause. Participants who have not died at the time of the final analysis will be censored at the date the participant was last known to be alive. The 90% CI was estimated using Kaplan-Meier methodology.
Objective Response Rate [From baseline up to 20 months]
Objective response rate (ORR) was defined by RECIST criteria as the best response achieved by a patient over the course of the trial, which includes 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, stable disease (SD), or progressive disease (PD). PR was defined as ≥ 30% decrease in sum of longest diameter of all target lesions, from baseline sum. CR was defined as disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. PD = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on the study.
Duration of Response [From baseline up to 20 months]
Duration of response was defined as the time from the first documented complete response (CR) or partial response (PR) to the first documented disease progression (PD) or death, whichever occurs first. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs taking as reference the Baseline SLD. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs.
Time to Response [From baseline up to 20 months]
This is defined for participants with objective response, as the date of randomization to the date of first CR or PR which will be the date the response is first radiographically documented following initiation of therapy (the date of the actual imaging modality).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

male or female patients >=18 years with histologically documented inoperable, locally advanced or metastatic (stage IIIB or IV) NSCLC;
patients must have failed at least one but no more than two standard chemotherapy regimens;
measurable disease according to the RECIST criteria;
Eastern Cooperative Oncology Group (ECOG) performance status;
life expectancy >12 weeks.

Exclusion Criteria:

patients with active central nervous system (CNS) lesions;
prior treatment with agents acting via insulin-like growth factor 1 receptor (IGF-1R) inhibition or epidermal growth factor receptor (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

Locations

	Site	City	State	Country	Postal Code
1	Tower Cancer Research Foundation	Beverly Hills	California	United States	90211
2	Florida Cancer Inst.	New Port Richey	Florida	United States	34655
3	Emory Univ Winship Cancer Inst	Atlanta	Georgia	United States	30322
4	University of Chicago Medical Center; Dept. of Medicine/Section of Nephrology	Chicago	Illinois	United States	60637
5	North Shore University Health System	Glenview	Illinois	United States	60026
6	Joliet Oncology Hematology Associates, Ltd.	Joliet	Illinois	United States	60435
7	St. Joseph Medical Center	Towson	Maryland	United States	21204
8	Massachusetts General Hospital.	Boston	Massachusetts	United States	02114
9	Dana Farber Cancer Inst.	Boston	Massachusetts	United States	02115
10	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
11	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
12	Carolina Oncology Specialists, PA - Hickory	Hickory	North Carolina	United States	28602
13	Chattanooga Oncology and Hematology Associates, PC	Chattanooga	Tennessee	United States	37404
14	Sarah Cannon Research Inst.	Nashville	Tennessee	United States	37203
15	Virginia Cancer Institute	Richmond	Virginia	United States	23226
16	Flinders Medical Center; Medical Oncology	Adelaide	South Australia	Australia	5041
17	Frankston Hospital; Oncology/Haematology	Frankston	Victoria	Australia	3199
18	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
19	Cliniques Universitaires St-Luc	Bruxelles		Belgium	1200
20	GHdC Site Notre Dame	Charleroi		Belgium	6000
21	UZ Antwerpen	Edegem		Belgium	2650
22	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
23	Chr de La Citadelle	Liege		Belgium	3500
24	Lakeridge Health Oshawa; Oncology	Oshawa	Ontario	Canada	L1G 2B9
25	Hopital Albert Michallon; Medecine Aigue Specialisee Pneumologie	La Tronche		France	38700
26	Hopital de La Croix Rousse; Service de Pneumologie	Lyon		France	69317
27	Fondation Hopital Saint Joseph; Pole Cancerologie, Imagerie Medicale Service d'Oncologie	Paris		France	75674
28	Hopital Tenon;Pneumologie	Paris		France	75970
29	Hopital Larrey; Clinique Des Voies Respiratoires	Toulouse		France	31400
30	Zentralklinik Bad Berka GmbH; Pneumologie	Bad Berka		Germany	99437
31	Helios Klinikum Emil von Behring GmbH	Berlin		Germany	14165
32	LungenClinic Großhansdorf GmbH	Großhansdorf		Germany	22927
33	Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin I	Halle (Saale)		Germany	06120
34	Asklepios Klinik Harburg; Thoraxzentrum	Hamburg		Germany	21075
35	Thoraxklinik Heidelberg gGmbH	Heidelberg		Germany	69126
36	Stiftung Kathol. Krankenhaus Marienhospital Herne Klinik Mitte Frauenklinik	Herne		Germany	44625
37	Klinikum Leverkusen; Med. Klinik III / Onkologie	Leverkusen		Germany	51375
38	Ludwig-Maximilians Uni Klinik Innenstadt; Medizinische Klinik	Muenchen		Germany	80336
39	St. James Hospital; Oncology	Dublin		Ireland	8
40	Arcispedale Santa Maria Nuova; Oncologia	Reggio Emilia	Emilia-Romagna	Italy	42100
41	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria	Italy	16132
42	Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia	Milano	Lombardia	Italy	20162
43	Az. Osp. S. Luigi Gonzaga; Malattie Apparato Respiratorio 5 Ad Indirizzo Oncologico	Orbassano	Piemonte	Italy	10043
44	Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica	Sant'Andrea Delle Fratte (PG)	Umbria	Italy	06132
45	Medical University of Gdansk	Gdansk		Poland	80-952
46	SK Przemienienia Panskiego UM im.K.Marcinkowskiego	Poznan		Poland	60-569
47	Specjalistyczny Szpital Im. Prof. A. Sokolowskiego; Oddziall Chemioterapii	Szczecin		Poland	70-891
48	Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii	Warszawa		Poland	02-781
49	Hospital Universitario Puerta de Hierro; Servicio de Oncologia	Majadahonda	Madrid	Spain	28222
50	Hospital de Cruces; Servicio de Oncologia	Bilbao	Vizcaya	Spain	48903
51	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona		Spain	08036
52	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona		Spain	08041
53	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga		Spain	29010
54	Royal Surrey County Hospital; St. Lukes Cancer Centre	Guildford		United Kingdom	GU2 7XX
55	Wythenshawe Hospital; North West Lung Centre	Manchester		United Kingdom	M23 9LT
56	Sir Bobby Robson Cancer Research Centre	Newcastle Upon Tyne		United Kingdom	NE7 7DN
57	New Cross Hospital; Deansley Centre	Wolverhampton		United Kingdom	WV10 0QP

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT00760929

Other Study ID Numbers:

NO21160
2008-001736-12

First Posted:

Sep 26, 2008

Last Update Posted:

Jan 5, 2021

Last Verified:

Dec 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Additional relevant MeSH terms:

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Erlotinib Hydrochloride

Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	A screening examination was to be performed between -28 and 1 days before first day of treatment.
Pre-assignment Detail	Safety population was used for the participant flow. All randomized participants who received at least one treatment. Two patients randomized to placebo QW actually received R1507 9 mg/kg QW.

Arm/Group Title	Placebo for R1507 (9mg/kg iv)	Placebo for R1507 (16mg/kg iv)	R1507 (9mg/kg iv)	R1507 (16mg/kg iv)
Arm/Group Description	Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression.	Participants received the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
Period Title: Overall Study
STARTED	26	29	59	57
COMPLETED	0	1	1	2
NOT COMPLETED	26	28	58	55

Baseline Characteristics

Arm/Group Title	Placebo for R1507 (9mg/kg iv)	Placebo for R1507 (16mg/kg iv)	R1507 (9mg/kg iv)	R1507 (16mg/kg iv)	Total
Arm/Group Description	Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression.	Participants received the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	Total of all reporting groups
Overall Participants	26	29	59	57	171
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.0 (8.01)	62.3 (8.26)	60.3 (10.45)	60.5 (9.82)	61.0 (9.56)
Sex: Female, Male (Count of Participants)
Female	9 34.6%	11 37.9%	18 30.5%	19 33.3%	57 33.3%
Male	17 65.4%	18 62.1%	41 69.5%	38 66.7%	114 66.7%
Race/Ethnicity, Customized (Count of Participants)
Black	0 0%	1 3.4%	1 1.7%	1 1.8%	3 1.8%
Hispanic	0 0%	1 3.4%	1 1.7%	0 0%	2 1.2%
White	26 100%	27 93.1%	57 96.6%	56 98.2%	166 97.1%
Smoking Status (Count of Participants)
Current smoker	3 11.5%	6 20.7%	8 13.6%	5 8.8%	22 12.9%
Never smoked	3 11.5%	4 13.8%	6 10.2%	7 12.3%	20 11.7%
Past smoker	20 76.9%	19 65.5%	45 76.3%	45 78.9%	129 75.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Progression Free Survival (PFS)
Description	PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]) based on RECIST tumor response criteria or died from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants who had not died or progressed at the time of the final analysis were censored at the date of last contact.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description
All-treated population: All participants enrolled in the study who had been randomly assigned to one of the four study treatments were included. For analysis, participants receiving both weekly and every 3 weeks of placebo were combined and evaluated as one group.

Arm/Group Title	Placebo	R1507 (9mg/kg iv)	R1507 (16mg/kg iv)
Arm/Group Description	Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression or the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
Measure Participants	57	57	57
Progression-Free & Alive	18 69.2%	16 55.2%	21 35.6%
Progressed, Died, or Unknown	39 150%	41 141.4%	36 61%

2. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the median time, in weeks, from the date of randomization to the date of death, due to any cause. Participants who have not died at the time of the final analysis will be censored at the date the participant was last known to be alive. The 90% CI was estimated using Kaplan-Meier methodology.
Time Frame	From baseline up to 20 months

Outcome Measure Data

Analysis Population Description
All-treated population: All participants enrolled in the study who had been randomly assigned to one of the four study treatments were included. For analysis, participants receiving both weekly and every 3 weeks of placebo were combined and evaluated as one group.

Arm/Group Title	Placebo	R1507 (9mg/kg iv)	R1507 (16mg/kg iv)
Arm/Group Description	Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression or the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
Measure Participants	57	57	57
Median (90% Confidence Interval) [Weeks]	35.1	35.1	52.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, R1507 (9mg/kg iv)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4301
	Comments
	Method	Wald Test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	() 90% 0.58 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, R1507 (16mg/kg iv)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0342
	Comments
	Method	Wald Test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.61
	Confidence Interval	() 90% 0.42 to 0.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Objective Response Rate
Description	Objective response rate (ORR) was defined by RECIST criteria as the best response achieved by a patient over the course of the trial, which includes 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, stable disease (SD), or progressive disease (PD). PR was defined as ≥ 30% decrease in sum of longest diameter of all target lesions, from baseline sum. CR was defined as disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. PD = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on the study.
Time Frame	From baseline up to 20 months

Outcome Measure Data

Analysis Population Description
All-treated population: All participants enrolled in the study who had been randomly assigned to one of the four study treatments were included. For analysis, participants receiving both weekly and every 3 weeks of placebo were combined and evaluated as one group.

Arm/Group Title	Placebo	R1507 (9mg/kg iv)	R1507 (16mg/kg iv)
Arm/Group Description	Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression or the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
Measure Participants	57	57	57
Number (95% Confidence Interval) [Percentage of Participants]	8.8 33.8%	7 24.1%	7 11.9%

4. Secondary Outcome

Title	Duration of Response
Description	Duration of response was defined as the time from the first documented complete response (CR) or partial response (PR) to the first documented disease progression (PD) or death, whichever occurs first. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs taking as reference the Baseline SLD. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs.
Time Frame	From baseline up to 20 months

Outcome Measure Data

Analysis Population Description
All-treated population: All participants enrolled in the study who had been randomly assigned to one of the four study treatments were included. For analysis, participants receiving both weekly and every 3 weeks of placebo were combined and evaluated as one group.

Arm/Group Title	Placebo	R1507 (9mg/kg iv)	R1507 (16mg/kg iv)
Arm/Group Description	Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression or the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
Measure Participants	5	4	4
Mean (Standard Deviation) [days]	260.40 (140.56)	215.50 (91.70)	257.75 (130.07)

5. Secondary Outcome

Title	Time to Response
Description	This is defined for participants with objective response, as the date of randomization to the date of first CR or PR which will be the date the response is first radiographically documented following initiation of therapy (the date of the actual imaging modality).
Time Frame	From baseline up to 20 months

Outcome Measure Data

Analysis Population Description
All-treated population: All participants enrolled in the study who had been randomly assigned to one of the four study treatments were included. For analysis, participants receiving both weekly and every 3 weeks of placebo were combined and evaluated as one group.

Arm/Group Title	Placebo	R1507 (9mg/kg iv)	R1507 (16mg/kg iv)
Arm/Group Description	Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression or the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.	Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.	Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
Measure Participants	5	4	4
Mean (Standard Deviation) [days]	42.40 (4.34)	65.25 (22.95)	85.25 (34.70)

Adverse Events

	Placebo for R1507 (9mg/kg iv)		Placebo for R1507 (16mg/kg iv)		R1507 (9mg/kg iv)		R1507 (16mg/kg iv)
Time Frame	Baseline up to 20 months
Adverse Event Reporting Description	Multiple occurrences of the same adverse event in one individual counted only once. Safety population was used for the participant flow. All randomized participants who received at least one treatment. Two patients randomized to placebo QW actually received R1507 9 mg/kg QW.

Arm/Group Title	Placebo for R1507 (9mg/kg iv)		Placebo for R1507 (16mg/kg iv)		R1507 (9mg/kg iv)		R1507 (16mg/kg iv)
Arm/Group Description	Participants received a placebo equivalent to R1507 (9mg/kg iv) intravenously every week until disease progression.		Participants received the placebo equivalent to R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.		Participants received R1507 (9mg/kg iv) intravenously every week until disease progression.		Participants received R1507 (16 mg/kg iv) intravenously every 3 weeks until disease progression.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/26 (76.9%)		22/29 (75.9%)		43/59 (72.9%)		34/57 (59.6%)
Serious Adverse Events
	Placebo for R1507 (9mg/kg iv)		Placebo for R1507 (16mg/kg iv)		R1507 (9mg/kg iv)		R1507 (16mg/kg iv)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/26 (19.2%)		3/29 (10.3%)		18/59 (30.5%)		14/57 (24.6%)
Blood and lymphatic system disorders
THROMBOCYTOPENIA	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
Cardiac disorders
MYOCARDIAL INFARCTION	0/26 (0%)	0	0/29 (0%)	0	2/59 (3.4%)	2	1/57 (1.8%)	1
ANGINA PECTORIS	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
ATRIAL FLUTTER	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
TACHYCARDIA	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
Gastrointestinal disorders
COLITIS	1/26 (3.8%)	1	1/29 (3.4%)	1	0/59 (0%)	0	0/57 (0%)	0
DIARRHOEA	0/26 (0%)		0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
DUODENAL ULCER HAEMORRHAGE	0/26 (0%)	0	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
LARGE INTESTINE PERFORATION	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
NAUSEA	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
PERITONITIS	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
STOMATITIS	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
General disorders
CHEST PAIN	0/26 (0%)	0	1/29 (3.4%)	1	0/59 (0%)	0	1/57 (1.8%)	1
GENERAL PHYSICAL HEALTH DETERIORATION	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	1/57 (1.8%)	1
ASTHENIA	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
FATIGUE	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
Hepatobiliary disorders
CHOLELITHIASIS	0/26 (0%)	0	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
Infections and infestations
INFECTION	0/26 (0%)	0	0/29 (0%)	0	2/59 (3.4%)	2	1/57 (1.8%)	1
PNEUMONIA	1/26 (3.8%)	1	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
BACTERAEMIA	1/26 (3.8%)	1	0/29 (0%)	0	0/59 (0%)	0	0/57 (0%)	0
BACTERIAL INFECTION	0/26 (0%)	0	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
BRONCHITIS	1/26 (3.8%)	1	0/29 (0%)	0	0/59 (0%)	0	0/57 (0%)	0
BRONCHOPNEUMONIA	1/26 (3.8%)	1	0/29 (0%)	0	0/59 (0%)	0	0/57 (0%)	0
CELLULITIS	0/26 (0%)	0	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
DEVICE RELATED INFECTION	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
LOWER RESPIRATORY TRACT INFECTION	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
LUNG INFECTION	0/26 (0%)	0	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
SEPSIS	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
Metabolism and nutrition disorders
DECREASED APPETITE	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
FAILURE TO THRIVE	0/26 (0%)	0	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
HYPOVOLAEMIA	0/26 (0%)	0	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
NECK PAIN	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR PAIN	0/26 (0%)	0	1/29 (3.4%)	1	0/59 (0%)	0	0/57 (0%)	0
Nervous system disorders
ATAXIA	0/26 (0%)	0	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
CONVULSION	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
NEURALGIA	0/26 (0%)	0	1/29 (3.4%)	1	0/59 (0%)	0	0/57 (0%)	0
TRANSIENT ISCHAEMIC ATTACK	0/26 (0%)	0	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	1/57 (1.8%)	1
PNEUMONITIS	1/26 (3.8%)	1	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
RESPIRATORY FAILURE	1/26 (3.8%)	1	0/29 (0%)	0	1/59 (1.7%)	1	1/57 (1.8%)	1
CHRONIC OBSTRUCTIVE PULMONARY	0/26 (0%)		0/29 (0%)	0	0/59 (0%)	0	0/57 (0%)	0
EPISTAXIS	0/26 (0%)		0/29 (0%)	0	1/59 (1.7%)	1	1/57 (1.8%)	1
HAEMOTHORAX	0/26 (0%)		0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
PLEURAL EFFUSION	1/26 (3.8%)	1	0/29 (0%)	0	0/59 (0%)	0	0/57 (0%)	0
PNEUMOTHORAX	1/26 (3.8%)	1	0/29 (0%)	0	0/59 (0%)	0	0/57 (0%)	0
PULMONARY EMBOLISM	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
Skin and subcutaneous tissue disorders
EXFOLIATIVE RASH	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
RASH	0/26 (0%)	0	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
Vascular disorders
DEEP VEIN THROMBOSIS	0/26 (0%)	0	0/29 (0%)	0	1/59 (1.7%)	1	0/57 (0%)	0
PHLEBITIS	0/26 (0%)	0	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
THROMBOSIS	0/26 (0%)	0	0/29 (0%)	0	0/59 (0%)	0	1/57 (1.8%)	1
Other (Not Including Serious) Adverse Events
	Placebo for R1507 (9mg/kg iv)		Placebo for R1507 (16mg/kg iv)		R1507 (9mg/kg iv)		R1507 (16mg/kg iv)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/26 (100%)		27/29 (93.1%)		57/59 (96.6%)		56/57 (98.2%)
Blood and lymphatic system disorders
ANAEMIA	3/26 (11.5%)	3	4/29 (13.8%)	4	4/59 (6.8%)	4	1/57 (1.8%)	1
Gastrointestinal disorders
DIARRHOEA	10/26 (38.5%)	10	13/29 (44.8%)	13	30/59 (50.8%)	30	32/57 (56.1%)	32
NAUSEA	6/26 (23.1%)	6	4/29 (13.8%)	4	20/59 (33.9%)	20	19/57 (33.3%)	19
VOMITING	6/26 (23.1%)	6	5/29 (17.2%)	5	14/59 (23.7%)	14	7/57 (12.3%)	7
STOMATITIS	3/26 (11.5%)	3	3/29 (10.3%)	3	9/59 (15.3%)	9	15/57 (26.3%)	15
CONSTIPATION	3/26 (11.5%)	3	1/29 (3.4%)	1	9/59 (15.3%)	9	4/57 (7%)	4
DYSPEPSIA	1/26 (3.8%)	1	2/29 (6.9%)	2	6/59 (10.2%)	6	7/57 (12.3%)	7
ABDOMINAL PAIN	1/26 (3.8%)	1	0/29 (0%)	0	3/59 (5.1%)	3	3/57 (5.3%)	3
General disorders
FATIGUE	4/26 (15.4%)	4	7/29 (24.1%)	7	22/59 (37.3%)	22	23/57 (40.4%)	23
MUCOSAL INFLAMMATION	0/26 (0%)	0	4/29 (13.8%)	4	7/59 (11.9%)	7	11/57 (19.3%)	11
ASTHENIA	6/26 (23.1%)	6	2/29 (6.9%)	2	10/59 (16.9%)	10	2/57 (3.5%)	2
PYREXIA	1/26 (3.8%)	1	1/29 (3.4%)	1	3/59 (5.1%)	3	4/57 (7%)	4
Hepatobiliary disorders
HYPERBILIRUBINAEMIA	1/26 (3.8%)	1	3/29 (10.3%)	3	0/59 (0%)	0	2/57 (3.5%)	2
Infections and infestations
PARONYCHIA	0/26 (0%)	0	2/29 (6.9%)	2	5/59 (8.5%)	5	5/57 (8.8%)	5
NASOPHARYNGITIS	0/26 (0%)	0	2/29 (6.9%)	2	6/59 (10.2%)	6	2/57 (3.5%)	2
URINARY TRACT INFECTION	3/26 (11.5%)	3	0/29 (0%)	0	3/59 (5.1%)	3	2/57 (3.5%)	2
INFECTION	0/26 (0%)	0	1/29 (3.4%)	1	2/59 (3.4%)	2	2/57 (3.5%)	2
Investigations
WEIGHT DECREASED	1/26 (3.8%)	1	1/29 (3.4%)	1	15/59 (25.4%)	15	9/57 (15.8%)	9
BLOOD CREATININE INCREASED	0/26 (0%)	0	0/29 (0%)	0	2/59 (3.4%)	2	6/57 (10.5%)	6
Metabolism and nutrition disorders
DECREASED APPETITE	4/26 (15.4%)	4	8/29 (27.6%)	8	13/59 (22%)	13	22/57 (38.6%)	22
DEHYDRATION	1/26 (3.8%)	4	1/29 (3.4%)	1	3/59 (5.1%)	3	5/57 (8.8%)	5
HYPERGLYCAEMIA	0/26 (0%)	0	0/29 (0%)	0	2/59 (3.4%)	2	5/57 (8.8%)	5
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS	2/26 (7.7%)	2	1/29 (3.4%)	1	8/59 (13.6%)	8	12/57 (21.1%)	12
BACK PAIN	2/26 (7.7%)	2	4/29 (13.8%)	4	1/59 (1.7%)	1	4/57 (7%)	4
ARTHRALGIA	1/26 (3.8%)	1	1/29 (3.4%)	1	6/59 (10.2%)	6	2/57 (3.5%)	2
MUSCULOSKELETAL CHEST PAIN	2/26 (7.7%)	2	1/29 (3.4%)	1	2/59 (3.4%)	2	2/57 (3.5%)	2
MUSCULAR WEAKNESS	2/26 (7.7%)	2	0/29 (0%)	0	0/59 (0%)	0	0/57 (0%)	0
Nervous system disorders
DYSGEUSIA	2/26 (7.7%)	2	2/29 (6.9%)	2	7/59 (11.9%)	7	6/57 (10.5%)	6
DIZZINESS	4/26 (15.4%)	4	3/29 (10.3%)	3	5/59 (8.5%)	5	2/57 (3.5%)	2
HEADACHE	1/26 (3.8%)	1	1/29 (3.4%)	1	4/59 (6.8%)	4	6/57 (10.5%)	6
PARAESTHESIA	3/26 (11.5%)	12	1/29 (3.4%)	3	2/59 (3.4%)	3	1/57 (1.8%)	2
NEUROPATHY PERIPHERAL	3/26 (11.5%)	3	0/29 (0%)	0	2/59 (3.4%)	2	1/57 (1.8%)	1
Psychiatric disorders
DEPRESSION	0/26 (0%)	0	3/29 (10.3%)	3	0/59 (0%)	0	0/57 (0%)	0
HALLUCINATION	0/26 (0%)	0	2/29 (6.9%)	2	0/59 (0%)	0	0/57 (0%)	0
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	7/26 (26.9%)	7	4/29 (13.8%)	4	8/59 (13.6%)	8	10/57 (17.5%)	10
COUGH	6/26 (23.1%)	6	3/29 (10.3%)	3	9/59 (15.3%)	9	10/57 (17.5%)	10
EPISTAXIS	0/26 (0%)	0	1/29 (3.4%)	1	10/59 (16.9%)	10	12/57 (21.1%)	12
HAEMOPTYSIS	1/26 (3.8%)	1	1/29 (3.4%)	1	4/59 (6.8%)	4	4/57 (7%)	4
DYSPHONIA	1/26 (3.8%)	1	3/29 (10.3%)	3	1/59 (1.7%)	1	2/57 (3.5%)	2
Skin and subcutaneous tissue disorders
RASH	14/26 (53.8%)	14	16/29 (55.2%)	16	32/59 (54.2%)	32	42/57 (73.7%)	42
PRURITUS	2/26 (7.7%)	2	3/29 (10.3%)	3	5/59 (8.5%)	5	7/57 (12.3%)	7
DRY SKIN	3/26 (11.5%)	3	4/29 (13.8%)	4	5/59 (8.5%)	5	4/57 (7%)	4
NAIL DISORDER	1/26 (3.8%)	1	0/29 (0%)	0	2/59 (3.4%)	2	5/57 (8.8%)	5
DERMATITIS ACNEIFORM	0/26 (0%)	0	0/29 (0%)	0	3/59 (5.1%)	3	4/57 (7%)	4
ACNE	2/26 (7.7%)	2	1/29 (3.4%)	1	1/59 (1.7%)	1	1/57 (1.8%)	1
ALOPECIA	0/26 (0%)	0	2/29 (6.9%)	2	2/59 (3.4%)	2	2/57 (3.5%)	2
DERMATITIS	0/26 (0%)	0	0/29 (0%)	0	4/59 (6.8%)	4	0/57 (0%)	0
Vascular disorders
DEEP VEIN THROMBOSIS	0/26 (0%)	0	0/29 (0%)	0	4/59 (6.8%)	4	1/57 (1.8%)	1

Limitations/Caveats

Development of the study drug R1570 was discontinued based on the available clinical data and the large number of molecules targeting the pathway. Not all efficacy parameters described in the protocol were assessed.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

Name/Title	Study Director
Organization	F. Hoffmann-La Roche AG
Phone	+41 616878333
Email	global.trial_information@roche.com

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT00760929

Other Study ID Numbers:

NO21160
2008-001736-12

First Posted:

Sep 26, 2008

Last Update Posted:

Jan 5, 2021

Last Verified:

Dec 1, 2020

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).

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact