Study of Oral Topotecan With Bevacizumab for Recurrent Small Cell Lung Cancer

An Open-label, Multicenter, Non-comparative, Phase II Study of Oral Topotecan in Combination With Bevacizumab for Second-line Treatment in Subjects With Relapsed Small-cell Lung Cancer (SCLC)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00698516

Enrollment

Registered

2008-06-17

Start date

2008-07-31

Completion date

2010-05-31

Last updated

2012-03-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lung Cancer, Small Cell, Recurrent Small-cell Lung Cancer (SCLC)

Keywords

Bevacizumab, Small Cell Lung Cancer (SCLC), Topotecan

Brief summary

Combination of Hycamtin (topotecan) and Avastin (bevacizumab) could allow killing of both endothelial and neoplastic cells. We postulate that addition of bevacizumab to topotecan will increase delivery of topotecan to tumor cells and may enhance activity of topotecan in patients with previously treated small cell lung cancer and improve progression free survival.

Interventions

DRUGOral Hycamtin (topotecan) Capsules + IV Avastin (bevacizumab)

2.3 mg/m2 daily x 5 oral topotecan and 15 mg/kg IV bevacizumab on day 1 of every 21 days cycle.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Histologically or cytologically confirmed diagnosis of SCLC. * First recurrence of SCLC after therapy with one prior chemotherapy regimen at initial diagnosis. * Relapsed SCLC of any duration (both sensitive and resistant relapse). * ECOG performance status of \</= 2. * Adequate bone marrow reserve, hepatic, renal, and cardiovascular function. * No prior therapy with bevacizumab or any other VEGF inhibitor or topotecan

Exclusion criteria

* Uncontrolled emesis, regardless of etiology. * Active uncontrolled infection. * GI conditions or drugs that could impact absorption of oral topotecan. * Known hypersensitivity to any component of topotecan capsule or compounds chemically related to topotecan. * Uncontrolled hypertension with BP\>150/100. * Prior h/o hypertensive crisis or encephalopathy. * NYHA Grade II or greater congestive heart failure. * H/O myocardial infarction within 6 months. * H/O stroke or TIA within 6 months. * H/O thrombotic or hemorrhagic disorders. * Clinically significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months. * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days. * Anticipation of need for major surgical procedure during the study. * Minor surgical procedures within 7 days prior to treatment start (placement of vascular access devices is permitted). * H/O abdominal fistula, GI perforation, or intra-abdominal abscess within prior 6 months. Serious, non-healing wound, active ulcer, or untreated bone fracture. - H/O hemoptysis within prior 1 month. * Concurrent radiotherapy. * H/O whole lung radiation within 90 days prior to start of treatment. * Presence or h/o central nervous system or brain metastases. * H/o another malignancy other than SCLC. * Concurrent chemotherapy, immunotherapy, or investigational therapy for the treatment of small cell lung cancer.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Progression-free Survival (PFS) at 3 Months	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.

Secondary

Measure	Time frame	Description
Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)	Baseline to disease progression or death (up to 82.4 weeks)	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.
Number of Participants With a Tumor Response (CR and PR)	Baseline to disease progression or death (up to 82.4 weeks)	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.
PFS - Overall	Baseline to disease progression or death (up to 82.4 weeks)	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.
Time to Tumor Response (CR and PR)	Baseline to disease progression or death (up to 82.4 weeks)	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).
Overall Survival	Baseline to disease progression or death (up to 82.4 weeks)	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.
Duration of Tumor Response (CR and PR)	Baseline to disease progression or death (up to 82.4 weeks)	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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.	50
Total	50

Arm

Count

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.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Study Termination	2
Overall Study	Withdrawal by Subject	3

Baseline characteristics

Characteristic	Topotecan and Bevacizumab
Age Continuous	60.8 Years STANDARD_DEVIATION 10.75
Race/Ethnicity, Customized African American/African Heritage	6 participants
Race/Ethnicity, Customized White	43 participants
Race/Ethnicity, Customized White and Mixed Race	1 participants
Sex: Female, Male Female	26 Participants
Sex: Female, Male Male	24 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	50 / 50
serious Total, serious adverse events	18 / 50

Outcome results

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.

Time frame: 3 months

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

Arm	Measure	Value (NUMBER)
Topotecan and Bevacizumab	Percentage of Participants With Progression-free Survival (PFS) at 3 Months	65 percentageof participants

p-value: 0.01795% CI: [49.3, 76.9]Z statistic

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.