First-line Treatment Of Subjects With Extensive Disease Small Cell Lung Cancer With Weekly Hycamtin And Paraplatin

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00316186
• Collaborator: (none)
• Enrollment: 33
• Locations: 13
• Arm: 1
• Duration (Months): 47
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study was designed to find the safest and most effective dose of a combination of two chemotherapy drugs, Hycamtin® (topotecan) and Paraplatin® (carboplatin), in people with extensive disease small cell lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer, Small Cell	Drug: topotecan; Drug: carboplatin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Phase II Study of Weekly Intravenous Hycamtin and Carboplatin as First-line Treatment of Chemonaive Subjects With Extensive Disease Small Cell Lung Cancer
• Study Start Date: Jun 1, 2005
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single arm, open label	Drug: topotecan; Hycamtin and Carboplatin as first-line treatment of chemonaive subjects with EX-SCLC.; Drug: carboplatin; Hycamtin and Carboplatin as first-line treatment of chemonaive subjects with EX-SCLC.; Other Names: topotecan

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate, as Determined by Radiologic Evaluation (Utilizing the World Health Organization [WHO] Criteria), Calculated as the Number of Participants With the Indicated Response [Baseline until up to Day 169]

   The categories of tumor response were: complete response (complete disappearance of all known lesions determined by 2 measurements not less than 4 weeks apart), partial response (>50% decrease in measurable lesions for at least 4 weeks with no appearance of new lesions), stable disease (no change in tumor size for at least 8 weeks), progressive disease (>25% increase in measurements of lesions or appearance of new lesions), and not evaluable. The overall response rate was determined using a scan performed within the first 30 days of the first response.

Secondary Outcome Measures

1. Time to Response [From start of treatment to evidence of partial or complete response]

   Time to response is calculated as the time from the start of treatment until first documented evidence of partial or complete response. The study was terminated after the dose-finding run-in component was completed because of slow recruitment and acknowledgement of a competing Phase II study. Data not available, as the activity stage was not done.

2. Response Duration [From time of partial or complete response to disease progression/death]

   Duration of response is calculated as the time from first documented partial or complete response until first documented sign of disease progression or death. The study was terminated after the dose-finding run-in component was completed because of slow recruitment and acknowledgement of a competing Phase II study. Data not available.

3. Time to Progression [From start of treatment to disease progression/death]

   Time to progression is defined as the time from the start of treatment until the first documented sign of disease progression or death due to any cause, if sooner. The study was terminated after the dose-finding run-in component was completed because of slow recruitment and acknowledgement of a competing Phase II study. Data not available.

4. Overall Survival, Calculated as the Number of Subjects Who Died From the Start of Treatment Until Follow-up [Week 1 up to maximum of Day 519]

   Overall survival is defined as the time from the start of treatment until death due to any cause. The study was terminated after the dose-finding run-in component was completed because of slow recruitment and acknowledgement of a competing Phase II study. Data not available, as the activity stage of the study was not conducted.

5. Grade 1 (Mild) Hematological Toxicities [Week 1 through Endpoint (variable based on disease progression or toxicity)]

   Hematology evaluation included hemoglobin, hematocrit, red blood cell count, white blood cell with differential and platelet count. Differential included neutrophils, bands, lymphocytes, monocytes, eosinophils, and basophils. The intensity of each hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs). Hematological toxicities are summarized by Common Terminology Criteria (CTC) V3.0 Maximum Toxicity Grade.

6. Grade 2 (Moderate) Hematological Toxicities [Week 1 through Endpoint (variable based on disease progression or toxicity]

   Hematology evaluation included hemoglobin, hematocrit, red blood cell count, white blood cell with differential and platelet count. Differential included neutrophils, bands, lymphocytes, monocytes, eosinophils, and basophils. The intensity of each hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs). Hematological toxicities are summarized by Common Terminology Criteria (CTC) V3.0 Maximum Toxicity Grade.

7. Grade 3 (Severe) Hematological Toxicities [Week 1 through Endpoint (variable based on disease progression or toxicity]

   Hematology evaluation included hemoglobin, hematocrit, red blood cell count, white blood cell with differential and platelet count. Differential included neutrophils, bands, lymphocytes, monocytes, eosinophils, and basophils. The intensity of each hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs). Hematological toxicities are summarized by Common Terminology Criteria (CTC) V3.0 Maximum Toxicity Grade.

8. Grade 4 (Life-threatening or Disabling) Hematological Toxicities [Week 1 through Endpoint (variable based on disease progression or toxicity]

   Hematology evaluation included hemoglobin, hematocrit, red blood cell count, white blood cell with differential and platelet count. Differential included neutrophils, bands, lymphocytes, monocytes, eosinophils, and basophils. The intensity of each hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs). Hematological toxicities are summarized by Common Terminology Criteria (CTC) V3.0 Maximum Toxicity Grade.

Eligibility Criteria

Criteria

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

Inclusion criteria:

• Adequate contraception methods include: systemic contraceptives or IUD for 3 months prior to start of the study medication or diaphragm plus spermicide; for males, condom plus spermicide; or total abstinence from sexual intercourse during the course of the study

• Women of childbearing potential and sexually active males must practice or use an accepted and effective form of contraception

• Subjects who present with CNS metastases are eligible, provided the attending physician ascertains that the metastases are controlled before the start of chemotherapy, and the subject is asymptomatic on neurologic exam and is not receiving corticosteroid therapy to control symptoms. Continued use of other anti-seizure medication is permitted

• Free of active infection

• At screening, a probable life expectancy of at least 3 months

• No prior chemotherapy for SCLC or any chemotherapy within 5 years of the diagnosis of SCLC. Prior radiation to any symptomatic site is permitted provided that the indicator lesion site(s) are not irradiated, and radiation is completed before chemotherapy is started

• Performance status ECOG 0-1

• Adequate hematologic, renal and hepatic function •Hematologic: ANC 1500/mm3 [1.5 x 109/L], platelet count 100,000/L (100 x 109/L), hemoglobin 9.0 g/dL

• Renal: Serum Creatinine ≤1.5mg/dL (133mol/L) and CrCl 60 ml/min (Cockroft-Gault) [Cockroft, 1976]

CrCl may be calculated using the Cockcroft-Gault formula:

CrCl (ml/min) = Q x (140-age [yr]) x body wt [kg] 72 x serum creatinine [mg/dl] Q = 0.85 for females Q = 1.0 for males CrCl (ml/min) = K x (140-age [yr]) x body wt [kg] Serum creatinine [mol/L] K = 1.0 for females K = 1.23 for males

• Hepatic: Serum bilirubin (1.5 mg/dL), SGOT (AST), SGPT (ALT) and Alkaline Phosphatase 2 times the upper limit of normal (ULN) if liver metastases are absent by abdominal CT or MRI, or 5 times ULN if liver metastases are present

• At least 18 years old

• Written informed consent (subject's written understanding of and agreement to participate in this study.

• Subject with histologically-confirmed extensive small cell lung cancer or unequivocally positive positive cytological evidence (sputum, at least two, or aspirate biopsy)

• Presence of measurable disease according to World Health Organization (WHO)* criteria, as determined by diagnostic tests, including CT scan of the chest and abdomen, or MRI scan of the brain, or CXR, or PET CT, MRI, and/or CXR are the preferred diagnostic methods to evaluate disease during the course of this study. Use of positron-emission tomography (PET) is not required, but is permitted if it is the standard diagnostic tool employed by the institution. Measurable disease - Presence of at least one bidimensionally measurable, non-CNS lesion (indicator lesion). If the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology • Measurable disease, either on CT or MRI scan, requires one diameter 1 cm and one diameter 2 cm. • Measurable disease on CXR requires both diameters 2 cm. • Palpable tumor masses that could not be evaluated radiologically require two diameters 2 cm

• At least 3 weeks since last major surgery (a lesser period is acceptable if decided to be in the best interest of the subject).

• Subjects with central nervous system metastases are eligible as long as the attending doctor determines that the metastases are under control before the start of chemotherapy, and the subject has no symptoms of spreading of disease to the brain, and is not receiving drugs called steroids to control the symptoms.

• Laboratory criteria: Subjects must have adequate bone marrow reserve and adequate kidney and liver function.

Exclusion criteria:

• Concurrent or planned chemotherapy, immunotherapy, radiotherapy, or investigational therapy for the treatment of SCLC. (Concurrent radiation for palliation of bone metastases and CNS lesions must be discussed with and approved by the GlaxoSmithKline Medical Monitor)

• Concurrent severe medical problems other than the diagnosis of SCLC, which would significantly limit full compliance with the study or expose the patient to extreme risk

• Concomitant malignancies or previous malignancies other than SCLC within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or localized low grade prostate cancer (contact GlaxoSmithKline Medical Monitor to discuss enrolment of subjects with low grade prostate cancer)

• Present clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed by CT or MRI brain scan, or corticosteroid treatment to control symptoms of brain metastases

• Uncontrolled infection

• Ongoing tumor or previous tumor other than lung cancer within the last 5 years.

• Symptoms of spreading of the disease to the brain that requires treatment with drugs called steroids

• Severe medical problems other than the diagnosis of SCLC that would limit the ability of the subject to follow study plan or that would expose the subject to extreme risk.

• Ongoing or planned chemotherapy, immunotherapy, radiation treatment, or other experimental drug therapy for the treatment of SCLC.

• Use of investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication

• Women who are pregnant or lactating.

• Women who can become pregnant who refuse to practice an adequate form of birth control.

• Subjects with history of allergic reaction to chemicals related to HYCAMTIN and PARAPLATIN.

• Subjects with pre-existing heart disease, such as congestive heart failure, irregular heartbeats that require treatment, and heart attack within the last 3-months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Tucson	Arizona	United States	85712
2	GSK Investigational Site	Concord	California	United States	94520
3	GSK Investigational Site	Sacramento	California	United States	95819
4	GSK Investigational Site	Boca Raton	Florida	United States	33486
5	GSK Investigational Site	Hollywood	Florida	United States	33021
6	GSK Investigational Site	Chicago	Illinois	United States	60612
7	GSK Investigational Site	Munster	Indiana	United States	46321
8	GSK Investigational Site	Metairie	Louisiana	United States	70006
9	GSK Investigational Site	St. Louis	Missouri	United States	63141
10	GSK Investigational Site	Bronx	New York	United States	10467
11	GSK Investigational Site	Amarillo	Texas	United States	79106
12	GSK Investigational Site	Richmond	Virginia	United States	23230
13	GSK Investigational Site	Poznan		Poland

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00316186
• Other Study ID Numbers: 104864/903
• First Posted: Apr 20, 2006
• Last Update Posted: May 7, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by GlaxoSmithKline: chemonaive; small cell lung cancer; untreated; Lung cancer; HYCAMTIN; first-line; extensive disease
• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Carboplatin; Topotecan

Study Results

Participant Flow

Arm/Group Title	Intravenous Topotecan and Carboplatin
Arm/Group Description	Administered Weekly (Days 1 and 8 for topotecan; Day 1 for carboplatin) every 21 days
Period Title: Overall Study
STARTED	33
COMPLETED	21
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Intravenous Topotecan and Carboplatin
Arm/Group Description	Administered Weekly (Days 1 and 8 for topotecan; Day 1 for carboplatin) every 21 days
Overall Participants	33
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.2 (9.45)
Sex: Female, Male (Count of Participants)
Female	8 24.2%
Male	25 75.8%
Race/Ethnicity, Customized (participants) [Number]
White	33 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate, as Determined by Radiologic Evaluation (Utilizing the World Health Organization [WHO] Criteria), Calculated as the Number of Participants With the Indicated Response
Description	The categories of tumor response were: complete response (complete disappearance of all known lesions determined by 2 measurements not less than 4 weeks apart), partial response (>50% decrease in measurable lesions for at least 4 weeks with no appearance of new lesions), stable disease (no change in tumor size for at least 8 weeks), progressive disease (>25% increase in measurements of lesions or appearance of new lesions), and not evaluable. The overall response rate was determined using a scan performed within the first 30 days of the first response.
Time Frame	Baseline until up to Day 169

Outcome Measure Data

Analysis Population Description

ITT (Intent to Treat): participants that received at least one dose of study drug

Arm/Group Title	Intravenous Topotecan and Carboplatin
Arm/Group Description	Administered Weekly (Days 1 and 8 for topotecan; Day 1 for carboplatin) every 21 days
Measure Participants	33
Complete Response	0 0%
Partial Response	8 24.2%
Stable Disease	11 33.3%
Progressive Disease	6 18.2%
Not Evaluable	8 24.2%

2. Secondary Outcome

Title	Time to Response
Description	Time to response is calculated as the time from the start of treatment until first documented evidence of partial or complete response. The study was terminated after the dose-finding run-in component was completed because of slow recruitment and acknowledgement of a competing Phase II study. Data not available, as the activity stage was not done.
Time Frame	From start of treatment to evidence of partial or complete response

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Topotecan and Carboplatin
Arm/Group Description	Administered Weekly (Days 1 and 8 for topotecan; Day 1 for carboplatin) every 21 days
Measure Participants	0

3. Secondary Outcome

Title	Response Duration
Description	Duration of response is calculated as the time from first documented partial or complete response until first documented sign of disease progression or death. The study was terminated after the dose-finding run-in component was completed because of slow recruitment and acknowledgement of a competing Phase II study. Data not available.
Time Frame	From time of partial or complete response to disease progression/death

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Topotecan and Carboplatin
Arm/Group Description	Administered Weekly (Days 1 and 8 for topotecan; Day 1 for carboplatin) every 21 days
Measure Participants	0

4. Secondary Outcome

Title	Time to Progression
Description	Time to progression is defined as the time from the start of treatment until the first documented sign of disease progression or death due to any cause, if sooner. The study was terminated after the dose-finding run-in component was completed because of slow recruitment and acknowledgement of a competing Phase II study. Data not available.
Time Frame	From start of treatment to disease progression/death

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Topotecan and Carboplatin
Arm/Group Description	Administered Weekly (Days 1 and 8 for topotecan; Day 1 for carboplatin) every 21 days
Measure Participants	0

5. Secondary Outcome

Title	Overall Survival, Calculated as the Number of Subjects Who Died From the Start of Treatment Until Follow-up
Description	Overall survival is defined as the time from the start of treatment until death due to any cause. The study was terminated after the dose-finding run-in component was completed because of slow recruitment and acknowledgement of a competing Phase II study. Data not available, as the activity stage of the study was not conducted.
Time Frame	Week 1 up to maximum of Day 519

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Topotecan and Carboplatin
Arm/Group Description	Administered Weekly (Days 1 and 8 for topotecan; Day 1 for carboplatin) every 21 days
Measure Participants	0

6. Secondary Outcome

Title	Grade 1 (Mild) Hematological Toxicities
Description	Hematology evaluation included hemoglobin, hematocrit, red blood cell count, white blood cell with differential and platelet count. Differential included neutrophils, bands, lymphocytes, monocytes, eosinophils, and basophils. The intensity of each hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs). Hematological toxicities are summarized by Common Terminology Criteria (CTC) V3.0 Maximum Toxicity Grade.
Time Frame	Week 1 through Endpoint (variable based on disease progression or toxicity)

Outcome Measure Data

Analysis Population Description

ITT Population (i.e., participants who had at least one dose of study medication)

Arm/Group Title	Intravenous Topotecan and Carboplatin
Arm/Group Description	Administered Weekly (Days 1 and 8 for topotecan; Day 1 for carboplatin) every 21 days
Measure Participants	32
Anemia	12 36.4%
Neutropenia	1 3%
Thrombocytopenia	15 45.5%
Leukopenia	13 39.4%

7. Secondary Outcome

Title	Grade 2 (Moderate) Hematological Toxicities
Description	Hematology evaluation included hemoglobin, hematocrit, red blood cell count, white blood cell with differential and platelet count. Differential included neutrophils, bands, lymphocytes, monocytes, eosinophils, and basophils. The intensity of each hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs). Hematological toxicities are summarized by Common Terminology Criteria (CTC) V3.0 Maximum Toxicity Grade.
Time Frame	Week 1 through Endpoint (variable based on disease progression or toxicity

Outcome Measure Data

Analysis Population Description

ITT Population (i.e., participants who had at least one dose of study medication)

Arm/Group Title	Intravenous Topotecan and Carboplatin
Arm/Group Description	Administered Weekly (Days 1 and 8 for topotecan; Day 1 for carboplatin) every 21 days
Measure Participants	32
Anemia	14 42.4%
Neutropenia	4 12.1%
Thrombocytopenia	5 15.2%
Leukopenia	10 30.3%

8. Secondary Outcome

Title	Grade 3 (Severe) Hematological Toxicities
Description	Hematology evaluation included hemoglobin, hematocrit, red blood cell count, white blood cell with differential and platelet count. Differential included neutrophils, bands, lymphocytes, monocytes, eosinophils, and basophils. The intensity of each hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs). Hematological toxicities are summarized by Common Terminology Criteria (CTC) V3.0 Maximum Toxicity Grade.
Time Frame	Week 1 through Endpoint (variable based on disease progression or toxicity

Outcome Measure Data

Analysis Population Description

ITT population (i.e., participants who had at least one dose of study medication)

Arm/Group Title	Intravenous Topotecan and Carboplatin
Arm/Group Description	Administered Weekly (Days 1 and 8 for topotecan; Day 1 for carboplatin) every 21 days
Measure Participants	32
Anemia	4 12.1%
Neutropenia	4 12.1%
Thrombocytopenia	2 6.1%
Leukopenia	4 12.1%

9. Secondary Outcome

Title	Grade 4 (Life-threatening or Disabling) Hematological Toxicities
Description	Hematology evaluation included hemoglobin, hematocrit, red blood cell count, white blood cell with differential and platelet count. Differential included neutrophils, bands, lymphocytes, monocytes, eosinophils, and basophils. The intensity of each hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs). Hematological toxicities are summarized by Common Terminology Criteria (CTC) V3.0 Maximum Toxicity Grade.
Time Frame	Week 1 through Endpoint (variable based on disease progression or toxicity

Outcome Measure Data

Analysis Population Description

ITT population (i.e., participants who had at least one dose of study medication)

Arm/Group Title	Intravenous Topotecan and Carboplatin
Arm/Group Description	Administered Weekly (Days 1 and 8 for topotecan; Day 1 for carboplatin) every 21 days
Measure Participants	32
Anemia	2 6.1%
Neutropenia	4 12.1%
Thrombocytopenia	2 6.1%
Leukopenia	0 0%

Adverse Events

Arm/Group Title	Intravenous Topotecan and Carboplatin
Arm/Group Description	Administered Weekly (Days 1 and 8 for topotecan; Day 1 for carboplatin) every 21 days
All Cause Mortality
	Intravenous Topotecan and Carboplatin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Intravenous Topotecan and Carboplatin
	Affected / at Risk (%)	# Events
Total	6/33 (18.2%)
Blood and lymphatic system disorders
Anemia	1/33 (3%)
Gastrointestinal disorders
Gastro-intestinal hemorrhage	1/33 (3%)
General disorders
Pyrexia	1/33 (3%)
Diease under study	1/33 (3%)
Nervous system disorders
Brain Mass	1/33 (3%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/33 (3%)
Respiratory failure	1/33 (3%)
Pulmonary hemorrhage	1/33 (3%)
Other (Not Including Serious) Adverse Events
	Intravenous Topotecan and Carboplatin
	Affected / at Risk (%)	# Events
Total	33/33 (100%)
Blood and lymphatic system disorders
Anemia	12/33 (36.4%)
Neutropenia	14/33 (42.4%)
Thrombocytopenia	13/33 (39.4%)
Leukopenia	2/33 (6.1%)
Cardiac disorders
Dyspnea	2/33 (6.1%)
Dyspnea exertional	2/33 (6.1%)
Eye disorders
Vision Blurred	2/33 (6.1%)
Gastrointestinal disorders
Nausea	5/33 (15.2%)
Constipation	4/33 (12.1%)
Vomiting	3/33 (9.1%)
Abdominal Pain	2/33 (6.1%)
General disorders
Fatigue	6/33 (18.2%)
Pyrexia	2/33 (6.1%)
Back Pain	2/33 (6.1%)
Infections and infestations
Mucosal inflammation	3/33 (9.1%)
Metabolism and nutrition disorders
Hyperuricemia	2/33 (6.1%)
Hypokalemia	2/33 (6.1%)
Nervous system disorders
Neuropathy peripheral	3/33 (9.1%)
Psychiatric disorders
Insomnia	2/33 (6.1%)
Respiratory, thoracic and mediastinal disorders
Chest Pain	4/33 (12.1%)
Cough	2/33 (6.1%)
Productive cough	2/33 (6.1%)
Skin and subcutaneous tissue disorders
Pruritus	2/33 (6.1%)
Rash	2/33 (6.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.