Study of Oral Topotecan With Bevacizumab for Recurrent Sm... | NCT00698516

NCT00698516

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
Open label, Single arm	Experimental	Oral topotecan + IV Bevacizumab	Drug: Oral Hycamtin (topotecan) Capsules + IV Avastin (bevacizumab)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Oral Hycamtin (topotecan) Capsules + IV Avastin (bevacizumab)	Drug	2.3 mg/m2 daily x 5 oral topotecan and 15 mg/kg IV bevacizumab on day 1 of every 21 days cycle.	Open label, Single arm

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Progression-free Survival (PFS) at 3 Months	PFS = time from initiation of drug to time of first disease progression/death due to any cause. Progression assessed using Response Evaluation Criteria (RECIST): >=20% increase in sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since treatment started, or appearance of new lesion(s). If participant did not progress or die, the time of initiation of post-treatment anti-cancer therapy or time of last contact used. PFS at 3 months calculated by taking the Kaplan-Meier (KM) estimate at 90 days from the initiation of treatment. SE = standard error.	3 months

Secondary Outcomes

Measure	Description	Time Frame
PFS - Overall	Progression-free survival at any site was defined as the time from initiation of investigational product to the time of first documented disease progression or death due to any cause. Progression was assessed using the RECIST guidelines: >= 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since treatment started, or appearance of new lesion (s). For participants who did not progress or die, the time of initiation of post-treatment anti-cancer therapy or the time of last contact was used.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Jonesboro	Arkansas	72401	United States
GSK Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
23391616	Derived	Spigel DR, Waterhouse DM, Lane S, Legenne P, Bhatt K. Efficacy and safety of oral topotecan and bevacizumab combination as second-line treatment for relapsed small-cell lung cancer: an open-label multicenter single-arm phase II study. Clin Lung Cancer. 2013 Jul;14(4):356-63. doi: 10.1016/j.cllc.2012.12.003. Epub 2013 Feb 4.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Topotecan and Bevacizumab	Participants were to receive oral topotecan 2.3 milligrams (mg)/meters squared (m^2)/day for 5 consecutive days (Days 1 to 5) and intravenous (IV) bevacizumab 15 mg/kilograms (kg) on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GlaxoSmithKline's study physician was needed for participants who required treatment beyond 8 cycles.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Topotecan and Bevacizumab	Participants were to receive oral topotecan 2.3 milligrams (mg)/meters squared (m^2)/day for 5 consecutive days (Days 1 to 5) and intravenous (IV) bevacizumab 15 mg/kilograms (kg) on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GlaxoSmithKline's study physician was needed for participants who required treatment beyond 8 cycles.

Units	Counts
Participants	BG00050

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00060.8± 10.75

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00026
Male	BG00024

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

White

Title	Measurements
	BG00043

African American/African Heritage

Title	Measurements
	BG000

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Progression-free Survival (PFS) at 3 Months

PFS = time from initiation of drug to time of first disease progression/death due to any cause. Progression assessed using Response Evaluation Criteria (RECIST): >=20% increase in sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since treatment started, or appearance of new lesion(s). If participant did not progress or die, the time of initiation of post-treatment anti-cancer therapy or time of last contact used. PFS at 3 months calculated by taking the Kaplan-Meier (KM) estimate at 90 days from the initiation of treatment. SE = standard error.

Intent-to-Treat (ITT) Population: all participants who received at least one dose of study medication

Posted

Number

percentageof participants

3 months

ID	Title	Description
OG000	Topotecan and Bevacizumab	Participants were to receive oral topotecan 2.3 milligrams (mg)/meters squared (m^2)/day for 5 consecutive days (Days 1 to 5) and intravenous (IV) bevacizumab 15 mg/kilograms (kg) on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GlaxoSmithKline's study physician was needed for participants who required treatment beyond 8 cycles.

Units	Counts
Participants	OG00050

Title

Denominators

Categories

Title	Measurements
	OG00065

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000		Z statistic	Z statistic was used to reject the null hypothesis provided Z>=1.65, where Z = (KM estimate at 3 months - null hypothesis value [50%])/Greenwood SE.	0.017	Historical data in target population showed 3-month PFS rates of <=50%. Oral topotecan with IV bevacizumab would provide clinically meaningful improvement in 3-month PFS if it could demonstrate a 40% improvement relative to the historical data.	Greenwood variance	65.0	Standard Error of the Mean	7.07	2-Sided	95	49.3	76.9				No	Superiority or Other

Secondary

PFS - Overall

Progression-free survival at any site was defined as the time from initiation of investigational product to the time of first documented disease progression or death due to any cause. Progression was assessed using the RECIST guidelines: >= 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since treatment started, or appearance of new lesion (s). For participants who did not progress or die, the time of initiation of post-treatment anti-cancer therapy or the time of last contact was used.

ITT Population

Posted

Median

95% Confidence Interval

weeks

Baseline to disease progression or death (up to 82.4 weeks)

ID	Title	Description
OG000	Topotecan and Bevacizumab: Resistant Participants	Participants were to receive oral topotecan 2.3 milligrams (mg)/meters squared (m^2)/day for 5 consecutive days (Days 1 to 5) and intravenous (IV) bevacizumab 15 mg/kilograms (kg) on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GlaxoSmithKline's study physician was needed for participants who required treatment beyond 8 cycles. The time to progression from the end of prior chemotherapy was <= 90 days; therefore, these participants were termed "resistant".
OG001	Topotecan and Bevacizumab: Sensitive Participants

Secondary

Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)

Tumor response was determined using the RECIST guidelines.CR, disappearance of all target lesions; PR, >=30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since treatment started; PD, >=20% increase in sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

ITT Population

Posted

Number

participants

Baseline to disease progression or death (up to 82.4 weeks)

ID	Title	Description
OG000	Topotecan and Bevacizumab: Resistant Participants	Participants were to receive oral topotecan 2.3 milligrams (mg)/meters squared (m^2)/day for 5 consecutive days (Days 1 to 5) and intravenous (IV) bevacizumab 15 mg/kilograms (kg) on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GlaxoSmithKline's study physician was needed for participants who required treatment beyond 8 cycles. The time to progression from the end of prior chemotherapy was <= 90 days; therefore, these participants were termed "resistant".
OG001	Topotecan and Bevacizumab: Sensitive Participants

Secondary

Number of Participants With a Tumor Response (CR and PR)

Tumor response was determined using the RECIST guidelines. CR: disappearance of all target lesions. PR: >=30% decrease in sum of LD of target lesions, taking as reference the baseline sum LD.

ITT Population

Posted

Number

participants

Baseline to disease progression or death (up to 82.4 weeks)

ID	Title	Description
OG000	Topotecan and Bevacizumab: Resistant Participants	Participants were to receive oral topotecan 2.3 milligrams (mg)/meters squared (m^2)/day for 5 consecutive days (Days 1 to 5) and intravenous (IV) bevacizumab 15 mg/kilograms (kg) on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GlaxoSmithKline's study physician was needed for participants who required treatment beyond 8 cycles. The time to progression from the end of prior chemotherapy was <= 90 days; therefore, these participants were termed "resistant".
OG001	Topotecan and Bevacizumab: Sensistive Participants	Participants were to receive oral topotecan 2.3 milligrams (mg)/meters squared (m^2)/day for 5 consecutive days (Days 1 to 5) and intravenous (IV) bevacizumab 15 mg/kilograms (kg) on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GlaxoSmithKline's study physician was needed for participants who required treatment beyond 8 cycles. The time to progression from the end of prior chemotherapy was >90 days; therefore, these participants were termed "sensitive".

Secondary

Duration of Tumor Response (CR and PR)

Tumor response was determined using the RECIST guidelines. CR: disappearance of all target lesions. PR: >=30% decrease in sum of LD of target lesions, taking as reference the baseline sum LD. Duration of response is defined as the time from start of response (CR or PR) until progression or death due to any cause. For participants who did not progress or die, the time of initiation of post-treatment anti-cancer therapy or the time of last contact was used.

Participants from the ITT Population who had CR and PR

Posted

Median

95% Confidence Interval

weeks

Baseline to disease progression or death (up to 82.4 weeks)

ID	Title	Description
OG000	Topotecan and Bevacizumab	Participants were to receive oral topotecan 2.3 milligrams (mg)/meters squared (m^2)/day for 5 consecutive days (Days 1 to 5) and intravenous (IV) bevacizumab 15 mg/kilograms (kg) on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GlaxoSmithKline's study physician was needed for participants who required treatment beyond 8 cycles.

Units	Counts
Participants

Secondary

Time to Tumor Response (CR and PR)

Tumor response was determined using the RECIST guidelines. CR: disappearance of all target lesions. PR: >=30% decrease in sum of LD of target lesions, taking as reference the baseline sum LD. Time to response is defined as the time from initiation of investigational product to the time of first documented response (CR or PR).

Participants from the ITT Population who had CR and PR

Posted

Median

95% Confidence Interval

weeks

Baseline to disease progression or death (up to 82.4 weeks)

ID	Title	Description
OG000	Topotecan and Bevacizumab	Participants were to receive oral topotecan 2.3 milligrams (mg)/meters squared (m^2)/day for 5 consecutive days (Days 1 to 5) and intravenous (IV) bevacizumab 15 mg/kilograms (kg) on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GlaxoSmithKline's study physician was needed for participants who required treatment beyond 8 cycles.

Units	Counts
Participants	OG000

Secondary

Overall Survival

Overall survival is defined as the time from initiation of investigational product to death due to any cause. For participants who did not die, the time of last contact was used.

ITT Population

Posted

Median

95% Confidence Interval

weeks

Baseline to disease progression or death (up to 82.4 weeks)

ID	Title	Description
OG000	Topotecan and Bevacizumab: Resistant Participants	Participants were to receive oral topotecan 2.3 milligrams (mg)/meters squared (m^2)/day for 5 consecutive days (Days 1 to 5) and intravenous (IV) bevacizumab 15 mg/kilograms (kg) on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GlaxoSmithKline's study physician was needed for participants who required treatment beyond 8 cycles. The time to progression from the end of prior chemotherapy was <= 90 days; therefore, these participants were termed "resistant".
OG001	Topotecan and Bevacizumab: Sensitive Participants	Participants were to receive oral topotecan 2.3 milligrams (mg)/meters squared (m^2)/day for 5 consecutive days (Days 1 to 5) and intravenous (IV) bevacizumab 15 mg/kilograms (kg) on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GlaxoSmithKline's study physician was needed for participants who required treatment beyond 8 cycles. The time to progression from the end of prior chemotherapy was >90 days; therefore, these participants were termed "sensitive".

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Topotecan and Bevacizumab	Participants were to receive oral topotecan 2.3 mg/m^2/day for 5 consecutive days (Days 1 to 5) and IV bevacizumab 15 mg/kg on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GSK's study physician was needed for subjects who required treatment beyond 8 cycles.			18	50	50	50

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected50 at risk
Sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected50 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Neutropenic infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected50 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Pain	General disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected50 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected50 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected50 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected50 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected50 at risk
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected50 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA	Systematic Assessment	EG0002 affected50 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Mental status changes	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Pericardial effusion	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk
Somnolence	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected50 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00030 affected50 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00027 affected50 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00019 affected50 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00017 affected50 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0006 affected50 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0004 affected50 at risk
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0004 affected50 at risk
Oral pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected50 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG00032 affected50 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG00012 affected50 at risk
Pain	General disorders	MedDRA	Systematic Assessment	EG0004 affected50 at risk
Chills	General disorders	MedDRA	Systematic Assessment	EG0003 affected50 at risk
Gait disturbance	General disorders	MedDRA	Systematic Assessment	EG0003 affected50 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0003 affected50 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00027 affected50 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00022 affected50 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00021 affected50 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00011 affected50 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0003 affected50 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00024 affected50 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00014 affected50 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0007 affected50 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0006 affected50 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0004 affected50 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00015 affected50 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00014 affected50 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00013 affected50 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0006 affected50 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0004 affected50 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0008 affected50 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0006 affected50 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0005 affected50 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0004 affected50 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0003 affected50 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0003 affected50 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0003 affected50 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG00010 affected50 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG00010 affected50 at risk
Dysgeusia	Nervous system disorders	MedDRA	Systematic Assessment	EG0006 affected50 at risk
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0006 affected50 at risk
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0006 affected50 at risk
Confusional state	Psychiatric disorders	MedDRA	Systematic Assessment	EG0005 affected50 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0004 affected50 at risk
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0008 affected50 at risk
Platelet count decreased	Investigations	MedDRA	Systematic Assessment	EG0004 affected50 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected50 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected50 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected50 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0006 affected50 at risk
Proteinuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0004 affected50 at risk
Fall	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0003 affected50 at risk
Hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0003 affected50 at risk

ID	Term
D055752	Small Cell Lung Carcinoma

Ancestor Terms

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D019772	Topotecan
D002214	Capsules
D000068258	Bevacizumab

Ancestor Terms

ID	Term
D002166	Camptothecin
D000470	Alkaloids
D006571	Heterocyclic Compounds
D004304	Dosage Forms
D004364	Pharmaceutical Preparations
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

Participants were to receive oral topotecan 2.3 milligrams (mg)/meters squared (m^2)/day for 5 consecutive days (Days 1 to 5) and intravenous (IV) bevacizumab 15 mg/kilograms (kg) on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GlaxoSmithKline's study physician was needed for participants who required treatment beyond 8 cycles. The time to progression from the end of prior chemotherapy was >90 days; therefore, these participants were termed "sensitive".