Trial Outcomes & Findings for Bendamustine as Second-Line Therapy in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer (NCT NCT00984542)

Last Updated: 2014-03-12

Results Overview

Estimated probable duration from on-study date to date of disease progression, using the Kaplan-Meier method with censoring (see analysis population description for additional details). Disease progression is defined under RECIST v1.1 as \>=20% increase in sum of longest diameters of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

On-study to date of progression, measured following cycle 2, 4, and 6 of a 21-day cycle for 6 cycles, (during 126 days)

Results posted on

2014-03-12

Participant Flow

This study opened to accrual in September 2009 and closed to accrual in February 2012

59 patients consented, 9 were determined to be ineligible to participate

Participant milestones

Participant milestones
Measure	Bendamustine Bendamustine 120 mg/m2 of body surface area intravenously on days 1 and 2 of a 21-day treatment cycle for a maximum of six cycles
Overall Study STARTED	50
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	41

Reasons for withdrawal

Reasons for withdrawal
Measure	Bendamustine Bendamustine 120 mg/m2 of body surface area intravenously on days 1 and 2 of a 21-day treatment cycle for a maximum of six cycles
Overall Study disease progression	19
Overall Study toxicity	7
Overall Study Death	7
Overall Study complicating disease	3
Overall Study Withdrawal by Subject	3
Overall Study clinical deterioration	2

Baseline Characteristics

Bendamustine as Second-Line Therapy in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bendamustine n=50 Participants Bendamustine 120 mg/m2 of body surface area intravenously on days 1 and 2 of a 21-day treatment cycle for a maximum of six cycles
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=5 Participants
Age, Categorical >=65 years	16 Participants n=5 Participants
Age, Continuous	62 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants
Region of Enrollment United States	50 participants n=5 Participants

PRIMARY outcome

Timeframe: On-study to date of progression, measured following cycle 2, 4, and 6 of a 21-day cycle for 6 cycles, (during 126 days)

Population: All patients are included in the analysis on intention-to treat basis. Analysis is by Kaplan-Meier method, where progression is an event, with censoring for non-progressed patients at greater of off-study date, last known alive date, or date of death not attributable to disease progression.

Outcome measures

Outcome measures
Measure	Bendamustine n=50 Participants Bendamustine 120 mg/m2 of body surface area intravenously on days 1 and 2 of a 21-day treatment cycle for a maximum of six cycles
Time to Progression	123 days Interval 98.0 to 138.0

SECONDARY outcome

Timeframe: Day 1 of each 21-day cycle for 6 cycles and at 30 days after end of treatment, at 156 days

Population: Total number of patients reported with any toxicity

Number of patients with worst-grade toxicity at each of five grades following NCI Common Toxicity Criteria with grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening/disabling, 5 = death.

Outcome measures

Outcome measures
Measure	Bendamustine n=50 Participants Bendamustine 120 mg/m2 of body surface area intravenously on days 1 and 2 of a 21-day treatment cycle for a maximum of six cycles
Number of Patients With Each Worst-grade Toxicity Number of patients with worst-grade toxicity of 1	1 participants
Number of Patients With Each Worst-grade Toxicity Number of patients with worst-grade toxicity of 2	14 participants
Number of Patients With Each Worst-grade Toxicity Number of patients with worst-grade toxicity of 3	21 participants
Number of Patients With Each Worst-grade Toxicity Number of patients with worst-grade toxicity of 4	5 participants
Number of Patients With Each Worst-grade Toxicity Number of patients with worst-grade toxicity of 5	9 participants

SECONDARY outcome

Timeframe: On-treatment date to date of disease progression, following cycle 2, 4, and 6 of a 21-day cycle for 6 cycles, (assessed up to 126 days)

Population: All patients with best overall response data; patients are excluded if best overall response data is missing or if the patient is non-evaluable for best overall response. 8 patients were not evaluable.

Number of patients in each response category, per RECIST v1.1, summarized as follows for target lesion criteria (see RECIST v1.1 for additional details): complete response (CR),disappearance of target lesions; partial response (PR), \>=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), \>=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.

Outcome measures

Outcome measures
Measure	Bendamustine n=42 Participants Bendamustine 120 mg/m2 of body surface area intravenously on days 1 and 2 of a 21-day treatment cycle for a maximum of six cycles
Best Response Complete Response	1 participants
Best Response Partial Response	10 participants
Best Response Progressive Disease	14 participants
Best Response Stable Disease	17 participants

SECONDARY outcome

Timeframe: On-study date to lesser of date of progression or date of death from any cause ,measured following cycle 2, 4, 6 of a 21-day cycle for 6 cycles, (assessed up to 126 days)

Population: All patients are included in the analysis on intention-to-treat basis. Analysis is by Kaplan-Meier method, where either death or progression is an event, with censoring for non-progressed, non-expired patients at greater of off-study date or last known alive date.

Estimated probable duration of life without disease progression, from on-study date to earlier of progression date or date of death from any cause, using the Kaplan-Meier method with censoring (see analysis population description for additional details). Disease progression is defined under RECIST v1.1 as \>=20% increase in sum of longest diameters of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions.

Outcome measures

Outcome measures
Measure	Bendamustine n=50 Participants Bendamustine 120 mg/m2 of body surface area intravenously on days 1 and 2 of a 21-day treatment cycle for a maximum of six cycles
Progression-free Survival	98 days Interval 61.0 to 114.0

SECONDARY outcome

Timeframe: On study to date of death from any cause or last date known alive, measured every 6-8 weeks from the end of treatment, up to 31 months

Population: All patients are included in the analysis on intention-to-treat basis. Analysis is by Kaplan-Meier method, where death is an event, with censoring for non-expired patients at greater of off-study date or last known alive date.

Estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method with censoring (see analysis population description for additional details)

Outcome measures

Outcome measures
Measure	Bendamustine n=50 Participants Bendamustine 120 mg/m2 of body surface area intravenously on days 1 and 2 of a 21-day treatment cycle for a maximum of six cycles
Overall Survival	144 days Interval 110.0 to 182.0

Adverse Events

Bendamustine

Serious events: 27 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bendamustine n=50 participants at risk Bendamustine 120 mg/m2 of body surface area intravenously on days 1 and 2 of a 21-day treatment cycle for a maximum of six cycles
Cardiac disorders atrial fibrillation	4.0% 2/50 • Number of events 2
Cardiac disorders troponin levels postive	2.0% 1/50 • Number of events 1
Vascular disorders clot, left upper arm	2.0% 1/50 • Number of events 1
General disorders chills	2.0% 1/50 • Number of events 1
Investigations creatine	2.0% 1/50 • Number of events 1
General disorders death not associated with CTCAE term-NOS	2.0% 1/50 • Number of events 1
General disorders death not associated with CTCAE term-disease progression	18.0% 9/50 • Number of events 9
Gastrointestinal disorders diarrhea	6.0% 3/50 • Number of events 3
Respiratory, thoracic and mediastinal disorders dyspnea	10.0% 5/50 • Number of events 5
General disorders fatigue	6.0% 3/50 • Number of events 3
General disorders fever in the absence of neutropenia, where neutropenia is defined as ANC < 1.0 x 10e9/L	4.0% 2/50 • Number of events 2
Musculoskeletal and connective tissue disorders hip fracture	6.0% 3/50 • Number of events 3
Metabolism and nutrition disorders glucose, serum-low	2.0% 1/50 • Number of events 1
Blood and lymphatic system disorders hemoglobin	6.0% 3/50 • Number of events 3
Respiratory, thoracic and mediastinal disorders hypoxia	4.0% 2/50 • Number of events 2
Infections and infestations infection-other	2.0% 1/50 • Number of events 1
Respiratory, thoracic and mediastinal disorders infection-documented with Grade 3 or 4 neutrophils-pneumonia	4.0% 2/50 • Number of events 2
Respiratory, thoracic and mediastinal disorders infection with normal ANC or Grade 1 or 2 neutrophils-bronchus	2.0% 1/50 • Number of events 1
Respiratory, thoracic and mediastinal disorders infection with normal ANC or Grade 1 or 2 neutrophils-lung	4.0% 2/50 • Number of events 2
Respiratory, thoracic and mediastinal disorders infection with unknown ANC-lung	2.0% 1/50 • Number of events 1
Gastrointestinal disorders nausea	8.0% 4/50 • Number of events 4
Blood and lymphatic system disorders neutrophils/granulocytes	4.0% 2/50 • Number of events 2
Gastrointestinal disorders pain-abdomen NOS	2.0% 1/50 • Number of events 1
Cardiac disorders chest pain	2.0% 1/50 • Number of events 1
Musculoskeletal and connective tissue disorders pain-right hip	2.0% 1/50 • Number of events 1
General disorders pain NOS	2.0% 1/50 • Number of events 1
Cardiac disorders pericardial effusion-non-malignant	2.0% 1/50 • Number of events 1
Respiratory, thoracic and mediastinal disorders pleural effusion	4.0% 2/50 • Number of events 2
Respiratory, thoracic and mediastinal disorders pneumonitis/pulmonary infiltrates	2.0% 1/50 • Number of events 1
Metabolism and nutrition disorders potassium, serum-low	2.0% 1/50 • Number of events 1
Respiratory, thoracic and mediastinal disorders acute respiratory distress	2.0% 1/50 • Number of events 1
Respiratory, thoracic and mediastinal disorders bilateral basilar pneumonia	2.0% 1/50 • Number of events 1
Respiratory, thoracic and mediastinal disorders pulomonary emboli-multiple	2.0% 1/50 • Number of events 1
Respiratory, thoracic and mediastinal disorders right lower lobe lung collapse	2.0% 1/50 • Number of events 1
Renal and urinary disorders acute renal failure	2.0% 1/50 • Number of events 1
Metabolism and nutrition disorders hyponatremia	2.0% 1/50 • Number of events 1
Nervous system disorders somnolence	2.0% 1/50 • Number of events 1
Vascular disorders superior vena cava syndrome	4.0% 2/50 • Number of events 2
Blood and lymphatic system disorders thrombocytopenia	4.0% 2/50 • Number of events 2
Gastrointestinal disorders vomiting	4.0% 2/50 • Number of events 2
Respiratory, thoracic and mediastinal disorders hemoptysis	2.0% 1/50 • Number of events 1
Respiratory, thoracic and mediastinal disorders pneumonia	8.0% 4/50 • Number of events 4

Other adverse events

Other adverse events
Measure	Bendamustine n=50 participants at risk Bendamustine 120 mg/m2 of body surface area intravenously on days 1 and 2 of a 21-day treatment cycle for a maximum of six cycles
Metabolism and nutrition disorders albumin, serum-low	12.0% 6/50 • Number of events 7
Investigations alkaline phosphatase	8.0% 4/50 • Number of events 5
Investigations Alanine aminotransferase, serum glutamic pyruvic transaminase (ALT, SGPT)	8.0% 4/50 • Number of events 5
Metabolism and nutrition disorders anorexia	32.0% 16/50 • Number of events 20
Investigations aspartate transaminase, serum glutamic oxaloacetic transaminase (AST, SGOT)	12.0% 6/50 • Number of events 7
Gastrointestinal disorders constipation	18.0% 9/50 • Number of events 9
General disorders constitutional symptoms-other	30.0% 15/50 • Number of events 51
Respiratory, thoracic and mediastinal disorders cough	16.0% 8/50 • Number of events 8
Skin and subcutaneous tissue disorders dermatology/skin-other	10.0% 5/50 • Number of events 7
Gastrointestinal disorders diarrhea	18.0% 9/50 • Number of events 13
Nervous system disorders dizziness	10.0% 5/50 • Number of events 7
Respiratory, thoracic and mediastinal disorders dyspnea	26.0% 13/50 • Number of events 13
General disorders edema-limb	8.0% 4/50 • Number of events 4
General disorders fatigue	50.0% 25/50 • Number of events 39
Metabolism and nutrition disorders calcium, serum-low	8.0% 4/50 • Number of events 4
Gastrointestinal disorders gastrointestinal-other	6.0% 3/50 • Number of events 3
Metabolism and nutrition disorders glucose, serum-high	16.0% 8/50 • Number of events 15
Blood and lymphatic system disorders hemoglobin	52.0% 26/50 • Number of events 49
Vascular disorders hypotension	6.0% 3/50 • Number of events 3
Psychiatric disorders insomnia	10.0% 5/50 • Number of events 5
Blood and lymphatic system disorders leukocytes	22.0% 11/50 • Number of events 26
Metabolism and nutrition disorders magnesium, serum-low	10.0% 5/50 • Number of events 8
Metabolism and nutrition disorders metabolic, laboratory-other	30.0% 15/50 • Number of events 31
Psychiatric disorders depression	6.0% 3/50 • Number of events 3
Gastrointestinal disorders mucositis (functional/symptomatic)-oral cavity	6.0% 3/50 • Number of events 3
Gastrointestinal disorders nausea	42.0% 21/50 • Number of events 24
Nervous system disorders neurology-other	6.0% 3/50 • Number of events 3
Nervous system disorders neuropathy-sensory	6.0% 3/50 • Number of events 4
Blood and lymphatic system disorders neutrophils/granulocytes	12.0% 6/50 • Number of events 9
Gastrointestinal disorders pain-abdomen NOS	8.0% 4/50 • Number of events 4
Musculoskeletal and connective tissue disorders pain-back	14.0% 7/50 • Number of events 7
Musculoskeletal and connective tissue disorders pain-extremity, limb	6.0% 3/50 • Number of events 3
Musculoskeletal and connective tissue disorders pain-joint	12.0% 6/50 • Number of events 6
Blood and lymphatic system disorders platelets	34.0% 17/50 • Number of events 31
Metabolism and nutrition disorders potassium, serum-low	12.0% 6/50 • Number of events 9
Respiratory, thoracic and mediastinal disorders pulmonary/upper respiratory-other	14.0% 7/50 • Number of events 11
Investigations sodium, serum-low	18.0% 9/50 • Number of events 14
Gastrointestinal disorders vomiting	28.0% 14/50 • Number of events 19
Investigations weight loss	20.0% 10/50 • Number of events 13

Additional Information

Leora Horn, MD

Vanderbilt-Ingram Cancer Center

Phone: 615-936-2033

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place