Topotecan and Carboplatin in the First-Line Treatment of Patients With Extensive Stage Small Cell Lung Cancer

• Sponsor: SCRI Development Innovations, LLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT00305942
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 61
• Locations: 16
• Arm: 1
• Duration (Months): 44.1
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This proposed phase II trial will investigate the combination of topotecan/carboplatin in the first-line treatment of patients with extensive-stage SCLC. Topotecan/platinum regimens are emerging as common treatments for patients with extensive-stage disease. This trial will be one of the first clinical trials to evaluate a combination of weekly topotecan and carboplatin in the first-line treatment of extensive-stage SCLC.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Small Cell	Drug: Topotecan; Drug: carboplatin	Phase 2

Detailed Description

Eligible patients will receive treatment with carboplatin and topotecan.

Topotecan 4mg/m2 IV on days 1, 8.

Carboplatin AUC=5 IV day 1 only .

• Cycles are repeated every 21 days for > 4 cycles of topotecan and carboplatin (maximum 6 courses). Restaging studies will be performed every 2 cycles (or 6 weeks.)

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Topotecan and Carboplatin in the First-Line Treatment of Patients With Extensive Stage Small Cell Lung Cancer
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Topotecan 4mg/m2 IV on days 1, 8. Carboplatin AUC=5 IV day 1 only . - Cycles are repeated every 21 days for > 4 cycles of topotecan and carboplatin (maximum 6 courses). Restaging studies will be performed every 2 cycles (or 6 weeks.)	Drug: Topotecan; Topotecan 4mg/m2 IV on days 1, 8.; Other Names: Hycamtin ; Drug: carboplatin; Carboplatin AUC=5 IV day 1 only .; Other Names: 41575-94-4

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment [18 months]

   Overall response rate is the percent of patients experiencing a complete or partial response by RECIST v. 1 Criteria. Overall response rate is the percentage of patients with complete response or partial response per RECIST v.1 Criteria. Complete response (CR) = Disappearance of all target lesions, disappearance of all nontarget lesions for at least 4 weeks. Partial Response (PR) = At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters. The final response category assigned represented the best response obtained during treatment.

Secondary Outcome Measures

1. Time to Progression (TTP), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease [18 months]

   Time to progression is defined as the interval between the start date of treatment and the date of occurrence of progressive disease.

2. Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death [18 months]

   Overall survival was measured from the date of study entry until the date of death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have confirmed small cell lung cancer with extensive stage disease. This includes patients with stage IIIB and IV disease.

• Patients with small cell histology are eligible. Large neuroendocrine or mixed small cell and non-small cell histology are not eligible.

• Patients must have measurable or evaluable disease.

• ECOG performance status 0 or 1.

• Patients must have adequate bone marrow, liver and kidney function

• The patients may have had no previous chemotherapy.

• Patients must be able to understand the nature of the study and give written informed consent.

Exclusion Criteria:

• Patients with limited stage disease. This includes IA, IB, IIA, IIB, and IIIA.

• Age < 18 years old.

• History of a prior malignancy within three years with the exception of skin cancer (excluding melanoma), cervical carcinoma in situ, in situ breast carcinoma or stage A/B prostate cancer.

• Female patients who are pregnant or are breast feeding

• History of acute myocardial infarction or stroke within 6 months.

• Uncontrolled hypertension, unstable angina, New York Heart Association grade II or greater CHF, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular disease.

• Patients who have received other investigational drugs within 28 days.

• Patients with CNS involvement (brain or meningeal). The single exception to this is the patient previously treated for brain metastases with radiation therapy, or surgical excision who has no evidence of active residual metastases on brain MRI at the time of study entry.

• Patients with large neuroendocrine tumor or mixed small cell and non-small cell histology

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northeast Alabama Regional Medical Center	Anniston	Alabama	United States	36207
2	Northeast Arkansas Clinic	Jonesboro	Arkansas	United States	72401
3	Florida Cancer Specialists	Fort Myers	Florida	United States	33901
4	Watson Clinic Center for Cancer Care and Research	Lakeland	Florida	United States	33805
5	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
6	Graves-Gilbert Clinic	Bowling Green	Kentucky	United States	42101
7	Consultants in Blood Disorders and Cancer	Louisville	Kentucky	United States	40207
8	Hematology Oncology Life Center	Alexandria	Louisiana	United States	71301
9	Mercy Hospital	Portland	Maine	United States	04101
10	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
11	Montana Cancer Institute Foundation	Missoula	Montana	United States	59802
12	Oncology Hematology Care	Cincinnati	Ohio	United States	45242
13	Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
14	Associates in Hematology Oncology	Chattanooga	Tennessee	United States	37404
15	Family Cancer Center	Collierville	Tennessee	United States	38017
16	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37023

Sponsors and Collaborators

• SCRI Development Innovations, LLC
• GlaxoSmithKline

Investigators

• Principal Investigator: David R. Spigel, MD, SCRI Development Innovations, LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Published article in the Journal of Thoracic Oncology

Publications

None provided.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT00305942
• Other Study ID Numbers: SCRI LUN 117
• First Posted: Mar 22, 2006
• Last Update Posted: Jan 31, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by SCRI Development Innovations, LLC: Lung Cancer; Carcinoma, Small Cell
• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Carcinoma, Small Cell; Carboplatin; Topotecan

Study Results

Participant Flow

Arm/Group Title	Topotecan/Carboplatin
Arm/Group Description	Topotecan 4mg/m2 IV on days 1, 8. Carboplatin AUC=5 IV day 1 only . - Cycles are repeated every 21 days for > 4 cycles of topotecan and carboplatin (maximum 6 courses). Restaging studies will be performed every 2 cycles (or 6 weeks.)
Period Title: Overall Study
STARTED	61
COMPLETED	23
NOT COMPLETED	38

Baseline Characteristics

Arm/Group Title	Topotecan/Carboplatin
Arm/Group Description	Topotecan 4mg/m2 IV on days 1, 8. Carboplatin AUC=5 IV day 1 only . - Cycles are repeated every 21 days for > 4 cycles of topotecan and carboplatin (maximum 6 courses). Restaging studies will be performed every 2 cycles (or 6 weeks.)
Overall Participants	61
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	24 39.3%
>=65 years	37 60.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66 (9.8)
Sex: Female, Male (Count of Participants)
Female	29 47.5%
Male	32 52.5%
Region of Enrollment (participants) [Number]
United States	61 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
Description	Overall response rate is the percent of patients experiencing a complete or partial response by RECIST v. 1 Criteria. Overall response rate is the percentage of patients with complete response or partial response per RECIST v.1 Criteria. Complete response (CR) = Disappearance of all target lesions, disappearance of all nontarget lesions for at least 4 weeks. Partial Response (PR) = At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters. The final response category assigned represented the best response obtained during treatment.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All patients were included in the analysis.

Arm/Group Title	Topotecan/Carboplatin
Arm/Group Description	Topotecan 4mg/m2 IV on days 1, 8. Carboplatin AUC=5 IV day 1 only . - Cycles are repeated every 21 days for > 4 cycles of topotecan and carboplatin (maximum 6 courses). Restaging studies will be performed every 2 cycles (or 6 weeks.)
Measure Participants	61
Number (95% Confidence Interval) [percentage of participants]	57 93.4%

2. Secondary Outcome

Title	Time to Progression (TTP), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease
Description	Time to progression is defined as the interval between the start date of treatment and the date of occurrence of progressive disease.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All patients were assessed for time to progression.

Arm/Group Title	Topotecan/Carboplatin
Arm/Group Description	Topotecan 4mg/m2 IV on days 1, 8. Carboplatin AUC=5 IV day 1 only . - Cycles are repeated every 21 days for > 4 cycles of topotecan and carboplatin (maximum 6 courses). Restaging studies will be performed every 2 cycles (or 6 weeks.)
Measure Participants	61
Median (95% Confidence Interval) [Months]	5.5

3. Secondary Outcome

Title	Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Description	Overall survival was measured from the date of study entry until the date of death.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All patients were assessed for overall survival.

Arm/Group Title	Topotecan/Carboplatin
Arm/Group Description	Topotecan 4mg/m2 IV on days 1, 8. Carboplatin AUC=5 IV day 1 only . - Cycles are repeated every 21 days for > 4 cycles of topotecan and carboplatin (maximum 6 courses). Restaging studies will be performed every 2 cycles (or 6 weeks.)
Measure Participants	61
Median (95% Confidence Interval) [Months]	8.5

Adverse Events

Arm/Group Title	Topotecan/Carboplatin
Arm/Group Description	Topotecan 4mg/m2 IV on days 1, 8. Carboplatin AUC=5 IV day 1 only . - Cycles are repeated every 21 days for > 4 cycles of topotecan and carboplatin (maximum 6 courses). Restaging studies will be performed every 2 cycles (or 6 weeks.)
All Cause Mortality
	Topotecan/Carboplatin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Topotecan/Carboplatin
	Affected / at Risk (%)	# Events
Total	28/61 (45.9%)
Blood and lymphatic system disorders
Hematoma	1/61 (1.6%)	1
Hemoglobin	3/61 (4.9%)	3
Hemorrhage, GI	1/61 (1.6%)	1
Neutrophils	1/61 (1.6%)	1
Pancytopenia (NOS)	2/61 (3.3%)	2
Platelets	3/61 (4.9%)	3
Cardiac disorders
Cardiac ischemia/infarction	1/61 (1.6%)	1
Conduction abnormality - Asystole	1/61 (1.6%)	1
Hypotension	1/61 (1.6%)	1
Gastrointestinal disorders
Gastrointestinal - Other (Gastroenteritis)	1/61 (1.6%)	1
Gastrointestinal - Other (Perforated diverticulum)	1/61 (1.6%)	1
Vomiting	1/61 (1.6%)	1
General disorders
Death not associated with CTCAE term - Disease Progression NOS	6/61 (9.8%)	6
Fever (NOS)	1/61 (1.6%)	1
Infections and infestations
Febrile Neutropenia	2/61 (3.3%)	2
Infection - Other (Cellulitis)	1/61 (1.6%)	1
Infection - Other (Pneumonia)	2/61 (3.3%)	2
Musculoskeletal and connective tissue disorders
Fracture	1/61 (1.6%)	1
Pain - back	1/61 (1.6%)	1
Nervous system disorders
Confusion	1/61 (1.6%)	1
Seizure	1/61 (1.6%)	1
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	1/61 (1.6%)	1
Dyspnea	1/61 (1.6%)	1
Hypoxemia	1/61 (1.6%)	1
Pain - chest	1/61 (1.6%)	1
Pleural effusion	1/61 (1.6%)	1
Pulmonary/Upper Respiratory - Other (Respiratory Failure)	1/61 (1.6%)	1
Other (Not Including Serious) Adverse Events
	Topotecan/Carboplatin
	Affected / at Risk (%)	# Events
Total	53/61 (86.9%)
Blood and lymphatic system disorders
Blood/Bone Marrow-Other	16/61 (26.2%)	26
Edema	11/61 (18%)	23
Hemoglobin	53/61 (86.9%)	200
Leukocytes (WBC)	46/61 (75.4%)	89
Neutrophils (ANC/AGC)	53/61 (86.9%)	156
Platelets	50/61 (82%)	150
Cardiac disorders
Cardiac-Other	4/61 (6.6%)	5
Hypotension	8/61 (13.1%)	11
Gastrointestinal disorders
Anorexia	22/61 (36.1%)	50
Constipation	26/61 (42.6%)	70
Dehydration	10/61 (16.4%)	18
Diarrhea	16/61 (26.2%)	20
Dysphagia	4/61 (6.6%)	5
Mucositis	5/61 (8.2%)	11
Nausea	26/61 (42.6%)	50
Pain (Abdomen-NOS)	6/61 (9.8%)	7
Taste Alteration	4/61 (6.6%)	14
Vomiting	16/61 (26.2%)	23
General disorders
Fatigue	52/61 (85.2%)	184
Fever	4/61 (6.6%)	5
Insomnia	11/61 (18%)	15
Pain	40/61 (65.6%)	96
Pain (NOS)	10/61 (16.4%)	13
Weight Loss	12/61 (19.7%)	23
Infections and infestations
Febrile Neutropenia	6/61 (9.8%)	7
Infection (Lung-Pneumonia)	6/61 (9.8%)	7
Infection (Urinary Tract-NOS)	5/61 (8.2%)	6
Metabolism and nutrition disorders
Alkaline Phospahatase	15/61 (24.6%)	26
ALT, SGPT	6/61 (9.8%)	9
AST, SGOT	9/61 (14.8%)	11
Hyperglycemia	22/61 (36.1%)	36
Hypoalbuminemia	11/61 (18%)	22
Hypocalcemia	7/61 (11.5%)	7
Hypokalemia	9/61 (14.8%)	10
Hyponatremia	9/61 (14.8%)	11
Metabolic/Laboratory - Other	10/61 (16.4%)	12
Musculoskeletal and connective tissue disorders
Arthralgia	10/61 (16.4%)	19
Myalgia	6/61 (9.8%)	12
Pain (back)	13/61 (21.3%)	19
Pain (bone)	13/61 (21.3%)	27
Pain (extremity-limb)	4/61 (6.6%)	7
Pain (joint)	7/61 (11.5%)	11
Nervous system disorders
Confusion	5/61 (8.2%)	7
Dizziness	6/61 (9.8%)	10
Mood Alteration (anxiety)	6/61 (9.8%)	6
Mood Alteration (Depression)	8/61 (13.1%)	12
Pain (headache)	5/61 (8.2%)	5
Sensory Neuropathy	5/61 (8.2%)	10
Respiratory, thoracic and mediastinal disorders
Cough	19/61 (31.1%)	27
Dyspnea	28/61 (45.9%)	52
Pain (chest/thorax-NOS)	11/61 (18%)	20
Pulmonary	22/61 (36.1%)	41
Pulmonary/Upper Respiratory-Other	4/61 (6.6%)	7
Voice Changes/Dysarthria	7/61 (11.5%)	8
Wheezing	5/61 (8.2%)	5
Skin and subcutaneous tissue disorders
Alopecia	14/61 (23%)	38
Skin	12/61 (19.7%)	14
Vascular disorders
Hemorrhage (Lung)	4/61 (6.6%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.