Effects of Carboplatin and Gemcitabine on Stage IIIB Pleural Effusion and Stage IV Lung Cancer

• Sponsor: Susanne Arnold (Other)
• Overall Status: Completed
• CT.gov ID: NCT00247416
• Collaborator: Kentucky Lung Cancer Research Program (Other)
• Enrollment: 60
• Locations: 7
• Arms: 2
• Duration (Months): 47
• Patients Per Site: 8.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to find better treatment for lung cancer and to find out what effects the combined treatment of carboplatin and gemcitabine when given with or without dexamethasone have on cancer.

This study will determine if dexamethasone, when given before standard chemotherapy will increase the cancer fighting effects and reduce the side effects of chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Stage IV Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer	Drug: Gemcitabine; Drug: Dexamethasone; Drug: Carboplatin	Phase 2

Detailed Description

Subjects enrolled in the study will be placed in one of two treatment arms. All subjects have a 50-50 chance of being placed into either treatment arm. Treatment Arm 1 will receive chemotherapy alone, Treatment Arm 2 will receive chemotherapy with dexamethasone given pre-treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Trail of Carboplatin and Gemcitabine Untreated Stage IIIB-pleural Effusion and Stage IV Lung Cancer
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: 1 No Dex No Dexamethasone	Drug: Gemcitabine; Gemcitabine 1000 mg/m^2 intravenously over 30 minutes on days 5 and 12.; Other Names: Gemzar ; Drug: Carboplatin; AUC 6.0 intravenously over 30 minutes on day 5.
Experimental: 2 Dex Dexamethasone	Drug: Gemcitabine; Gemcitabine 1000 mg/m^2 intravenously over 30 minutes on days 5 and 12.; Other Names: Gemzar ; Drug: Dexamethasone; 16 mg bid for 4 days prior to each chemotherapy start.; Drug: Carboplatin; AUC 6.0 intravenously over 30 minutes on day 5.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Reduction in Grade 3/4 Neutropenia [continuous throughout treatment, up to 25 weeks]

   Reduction grade 3/4 neutropenia

Secondary Outcome Measures

1. Effect of Dexamethasone Pre-treatment on Response Rate. [Pre-treatment, pre-cycles 3 & 5, and up to 4 weeks after last treatment]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

2. Effect of Dexamethasone Pre-treatment on Overall Survival. [Pre-treatment, pre-cycles 3 & 5,4 weeks after last treatment, every 3 months, an average of 471 days]

   Overall survival

3. Progression-free Survival [Pre-treatment, pre-cycles 3 & 5,4 weeks after last treatment, and every 3 months, an average of 471 days]

   progression-free survival

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Untreated, stage IIIB with pleural effusion

• Untreated, Stage IV, non-small cell lung cancer

• Recurrent after surgery if no previous radiation therapy or chemotherapy were administered as part of their primary treatment, except for palliative radiotherapy

• 18 years of age or older

• ECOG PS 0, 1 or 2

• At Least one target lesion according to the RECIST Criteria

• Adequate organ and marrow function

Exclusion Criteria:

• Previous cancer history unless they have had curative treatment completed at least 5 years prior to entry.

• No previous radiotherapy, chemotherapy or immunotherapy for NSCLC, except for radiation therapy to the brain to control metastasis, bone to control pain, or lung to relieve bronchial obstruction.

• No radiation therapy for any previous cancer to more than 25% of bone marrow.

• Uncontrolled, intercurrent illness

• Non-study corticosteroids

• Pregnant women

• Peripheral neuropathy greater than grade 1

• Uncontrolled seizures, central nervous system disorders

• Major surgery within 4 weeks of the start of study treatment

• Lack of complete recovery from major surgery.

• Glaucoma

• Lack of physical integrity of upper gastrointestinal tract, inability to swallow tablets

• Severe acquired or hereditary immunodeficiency

• Patients with brain metastases must receive definitive treatment (radiation, surgery or both) and be clinically and radiologically stable for 4 weeks & off corticosteroids for at least 2 weeks prior to randomization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Commonwealth Cancer Center	Danville	Kentucky	United States	40422
2	Markey Cancer Center	Lexington	Kentucky	United States	40536
3	Brown Cancer Center	Louisville	Kentucky	United States	40202
4	St. Claire Regional Medical Center	Morehead	Kentucky	United States	40351
5	Montgomery Cancer Center	Mt. Sterling	Kentucky	United States	40353
6	Owensboro Medical HealthCare System	Owensboro	Kentucky	United States	42303
7	West Kentucky Hematology & Oncology Group, PSC	Paducah	Kentucky	United States	42003

Sponsors and Collaborators

• Susanne Arnold
• Kentucky Lung Cancer Research Program

Investigators

• Principal Investigator: John Rinehart, Lucille P. Markey Cancer Center at University of Kentucky

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Susanne Arnold, Sponsor/Investigator, University of Kentucky
• ClinicalTrials.gov Identifier: NCT00247416
• Other Study ID Numbers: CTN-0501
• First Posted: Nov 1, 2005
• Last Update Posted: Mar 7, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by Susanne Arnold, Sponsor/Investigator, University of Kentucky: Untreated; Lung; Cancer; non-small cell; gemcitabine; gemzar; carboplatin; dexamethasone
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Pleural Effusion; Gemcitabine; Dexamethasone; Carboplatin

Study Results

Participant Flow

Pre-assignment Detail	Total number of patients enrolled is 60. However, 1 patient enrolled to trial was discontinued from trial prior to receipt of any study therapies; patient was randomized to arm 1 (control, no dexamethasone pretreatment) but received no study therapies or procedures.

Arm/Group Title	Arm 1, Control, no Dexamethasone Pretreatment	Arm 2, Dexamethasone Pretreatment Test Arm
Arm/Group Description	Patients with stage 4 untreated non-small cell lung cancer received carboplatin (AUC 6, day 1) and gemcitabine (1000 mg/m2 days 1, 8) for up to 6 cycles with no dexamethasone pretreatment.	Patients with stage 4 untreated non-small cell lung cancer received carboplatin (AUC 6, day 1) and gemcitabine (1000 mg/m2 days 1, 8) for up to 6 cycles with dexamethasone pretreatment.Dexamethasone pretreatment = dexamethasone 16 mg, bid 4 days before and day of each chemotherapy treatment (days 1 and 8).
Period Title: Overall Study
STARTED	26	33
COMPLETED	25	31
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Arm 1, Control, no Dexamethasone Pretreatment	Arm 2, Dexamethasone Pretreatment Test Arm	Total
Arm/Group Description	Patients with stage 4 untreated non-small cell lung cancer received carboplatin (AUC 6, day 1) and gemcitabine (1000 mg/m2 days 1, 8) for up to 6 cycles with no dexamethasone pretreatment.	Patients with stage 4 untreated non-small cell lung cancer received carboplatin (AUC 6, day 1) and gemcitabine (1000 mg/m2 days 1, 8) for up to 6 cycles with dexamethasone pretreatment.Dexamethasone pretreatment = dexamethasone 16 mg, bid 4 days before and day of each chemotherapy treatment (days 1 and 8).	Total of all reporting groups
Overall Participants	25	31	56
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 72%	27 87.1%	45 80.4%
>=65 years	7 28%	4 12.9%	11 19.6%
Sex: Female, Male (Count of Participants)
Female	13 52%	14 45.2%	27 48.2%
Male	12 48%	17 54.8%	29 51.8%
Region of Enrollment (participants) [Number]
United States	25 100%	31 100%	56 100%

Outcome Measures

1. Secondary Outcome

Title	Effect of Dexamethasone Pre-treatment on Response Rate.
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Pre-treatment, pre-cycles 3 & 5, and up to 4 weeks after last treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 No Dex	2 Dex
Arm/Group Description	No Dexamethasone Gemcitabine: Gemcitabine 1000 mg/m^2 intravenously over 30 minutes on days 5 and 12. Carboplatin: AUC 6.0 intravenously over 30 minutes on day 5.	Dexamethasone Gemcitabine: Gemcitabine 1000 mg/m^2 intravenously over 30 minutes on days 5 and 12. Dexamethasone: 16 mg bid for 4 days prior to each chemotherapy start. Carboplatin: AUC 6.0 intravenously over 30 minutes on day 5.
Measure Participants	25	31
Number (95% Confidence Interval) [percentage of responders out of total]	8	26

2. Primary Outcome

Title	Percentage of Participants With Reduction in Grade 3/4 Neutropenia
Description	Reduction grade 3/4 neutropenia
Time Frame	continuous throughout treatment, up to 25 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1, Control, no Dexamethasone Pretreatment	Arm 2, Dexamethasone Pretreatment Test Arm
Arm/Group Description	Patients with stage 4 untreated non-small cell lung cancer received carboplatin (AUC 6, day 1) and gemcitabine (1000 mg/m2 days 1, 8) for up to 6 cycles with no dexamethasone pretreatment.	Patients with stage 4 untreated non-small cell lung cancer received carboplatin (AUC 6, day 1) and gemcitabine (1000 mg/m2 days 1, 8) for up to 6 cycles with dexamethasone pretreatment.Dexamethasone pretreatment = dexamethasone 16 mg, bid 4 days before and day of each chemotherapy treatment (days 1 and 8).
Measure Participants	25	31
Number [percentage of participants]	40 160%	13 41.9%

3. Secondary Outcome

Title	Effect of Dexamethasone Pre-treatment on Overall Survival.
Description	Overall survival
Time Frame	Pre-treatment, pre-cycles 3 & 5,4 weeks after last treatment, every 3 months, an average of 471 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1, Control, no Dexamethasone Pretreatment	Arm 2, Dexamethasone Pretreatment Test Arm
Arm/Group Description	Patients with stage 4 untreated non-small cell lung cancer received carboplatin (AUC 6, day 1) and gemcitabine (1000 mg/m2 days 1, 8) for up to 6 cycles with no dexamethasone pretreatment.	Patients with stage 4 untreated non-small cell lung cancer received carboplatin (AUC 6, day 1) and gemcitabine (1000 mg/m2 days 1, 8) for up to 6 cycles with dexamethasone pretreatment.Dexamethasone pretreatment = dexamethasone 16 mg, bid 4 days before and day of each chemotherapy treatment (days 1 and 8).
Measure Participants	25	31
Median (95% Confidence Interval) [days]	291	378

4. Secondary Outcome

Title	Progression-free Survival
Description	progression-free survival
Time Frame	Pre-treatment, pre-cycles 3 & 5,4 weeks after last treatment, and every 3 months, an average of 471 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1, Control, no Dexamethasone Pretreatment	Arm 2, Dexamethasone Pretreatment Test Arm
Arm/Group Description	Patients with stage 4 untreated non-small cell lung cancer received carboplatin (AUC 6, day 1) and gemcitabine (1000 mg/m2 days 1, 8) for up to 6 cycles with no dexamethasone pretreatment.	Patients with stage 4 untreated non-small cell lung cancer received carboplatin (AUC 6, day 1) and gemcitabine (1000 mg/m2 days 1, 8) for up to 6 cycles with dexamethasone pretreatment.Dexamethasone pretreatment = dexamethasone 16 mg, bid 4 days before and day of each chemotherapy treatment (days 1 and 8).
Measure Participants	25	31
Median (95% Confidence Interval) [days]	101	122

Adverse Events

Arm/Group Title	1 No Dexamethasone		2 Dexamethasone
Arm/Group Description	Patients with stage 4 untreated non-small cell lung cancer received carboplatin (AUC 6, day 1) and gemcitabine (1000 mg/m2 days 1, 8) for up to 6 cycles with no dexamethasone pretreatment.		Patients with stage 4 untreated non-small cell lung cancer received carboplatin (AUC 6, day 1) and gemcitabine (1000 mg/m2 days 1, 8) for up to 6 cycles with dexamethasone pretreatment.Dexamethasone pretreatment = dexamethasone 16 mg, bid 4 days before and day of each chemotherapy treatment (days 1 and 8).
All Cause Mortality
	1 No Dexamethasone		2 Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	1 No Dexamethasone		2 Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/26 (26.9%)		12/33 (36.4%)
Blood and lymphatic system disorders
ANEMIA	0/26 (0%)		1/33 (3%)
LEUKOPENIA	0/26 (0%)		1/33 (3%)
THROMBOCYTOPENIA	1/26 (3.8%)		2/33 (6.1%)
Cardiac disorders
HEART ARREST	1/26 (3.8%)		1/33 (3%)
Gastrointestinal disorders
CONSTIPATION	2/26 (7.7%)		0/33 (0%)
DIARRHEA	0/26 (0%)		1/33 (3%)
DUODENAL ULCER	0/26 (0%)		1/33 (3%)
NAUSEA	1/26 (3.8%)		1/33 (3%)
RECTAL DISORDER	0/26 (0%)		1/33 (3%)
VOMITING	1/26 (3.8%)		0/33 (0%)
General disorders
MEDICATION ERROR	0/26 (0%)		1/33 (3%)
SEPSIS	0/26 (0%)		3/33 (9.1%)
Metabolism and nutrition disorders
HYPERGLYCEMIA	0/26 (0%)		1/33 (3%)
Musculoskeletal and connective tissue disorders
PATHOLOGICAL FRACTURE	1/26 (3.8%)		0/33 (0%)
Nervous system disorders
CEREBROVASCULAR ACCIDENT	0/26 (0%)		1/33 (3%)
DIZZINESS	1/26 (3.8%)		0/33 (0%)
Renal and urinary disorders
URINARY TRACT INFECTION	0/26 (0%)		1/33 (3%)
Respiratory, thoracic and mediastinal disorders
APNEA	0/26 (0%)		1/33 (3%)
COUGH INCREASED	0/26 (0%)		1/33 (3%)
DYSPNEA	1/26 (3.8%)		1/33 (3%)
HYPOXIA	0/26 (0%)		1/33 (3%)
PNEUMONIA	2/26 (7.7%)		3/33 (9.1%)
PULMONARY EMBOLUS	0/26 (0%)		3/33 (9.1%)
Vascular disorders
DEEP THROMBOPHLEBITIS	0/26 (0%)		1/33 (3%)
HYPOTENSION	0/26 (0%)		1/33 (3%)
MESENTERIC VENOUS OCCLUSION	0/26 (0%)		1/33 (3%)
THROMBOSIS	0/26 (0%)		1/33 (3%)
Other (Not Including Serious) Adverse Events
	1 No Dexamethasone		2 Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/26 (100%)		33/33 (100%)
Blood and lymphatic system disorders
ANEMIA	18/26 (69.2%)		24/33 (72.7%)
ECCHYMOSIS	3/26 (11.5%)		0/33 (0%)
HYPOCHROMIC ANEMIA	0/26 (0%)		3/33 (9.1%)
LEUKOCYTOSIS	0/26 (0%)		10/33 (30.3%)
LEUKOPENIA	18/26 (69.2%)		19/33 (57.6%)
PANCYTOPENIA	2/26 (7.7%)		0/33 (0%)
PETECHIA	3/26 (11.5%)		0/33 (0%)
THROMBOCYTHEMIA	0/26 (0%)		5/33 (15.2%)
THROMBOCYTOPENIA	18/26 (69.2%)		24/33 (72.7%)
Cardiac disorders
TACHYCARDIA	3/26 (11.5%)		0/33 (0%)
Endocrine disorders
CUSHINGS SYNDROME	0/26 (0%)		3/33 (9.1%)
Eye disorders
CONJUNCTIVITIS	0/26 (0%)		2/33 (6.1%)
Gastrointestinal disorders
ANOREXIA	5/26 (19.2%)		9/33 (27.3%)
CHOLECYSTITIS	2/26 (7.7%)		0/33 (0%)
CONSTIPATION	12/26 (46.2%)		18/33 (54.5%)
DIARRHEA	5/26 (19.2%)		8/33 (24.2%)
DYSPEPSIA	0/26 (0%)		2/33 (6.1%)
DYSPHAGIA	0/26 (0%)		2/33 (6.1%)
FLATULENCE	0/26 (0%)		2/33 (6.1%)
MOUTH ULCERATION	0/26 (0%)		4/33 (12.1%)
NAUSEA	16/26 (61.5%)		20/33 (60.6%)
ORAL MONILIASIS	0/26 (0%)		5/33 (15.2%)
RECTAL DISORDER	0/26 (0%)		2/33 (6.1%)
STOMATITIS	3/26 (11.5%)		9/33 (27.3%)
ULCERATIVE STOMATITIS	0/26 (0%)		2/33 (6.1%)
VOMITING	12/26 (46.2%)		7/33 (21.2%)
General disorders
ABDOMINAL PAIN	0/26 (0%)		3/33 (9.1%)
ACCIDENTAL INJURY	2/26 (7.7%)		0/33 (0%)
ASTHENIA	17/26 (65.4%)		23/33 (69.7%)
BACK PAIN	2/26 (7.7%)		3/33 (9.1%)
CHEST PAIN	3/26 (11.5%)		6/33 (18.2%)
FACE EDEMA	0/26 (0%)		2/33 (6.1%)
FEVER	7/26 (26.9%)		5/33 (15.2%)
HEADACHE	2/26 (7.7%)		3/33 (9.1%)
INJECTION SITE PAIN	3/26 (11.5%)		0/33 (0%)
INJECTION SITE REACTION	2/26 (7.7%)		0/33 (0%)
LAB TEST ABNORMAL	4/26 (15.4%)		7/33 (21.2%)
MUCOUS MEMBRANE DISORDER	2/26 (7.7%)		2/33 (6.1%)
PAIN	11/26 (42.3%)		7/33 (21.2%)
Infections and infestations
INFECTION FUNGAL	2/26 (7.7%)		0/33 (0%)
Metabolism and nutrition disorders
ALKALINE PHOSPHATASE INCREASED	0/26 (0%)		2/33 (6.1%)
BUN INCREASED	0/26 (0%)		3/33 (9.1%)
CREATININE INCREASED	0/26 (0%)		3/33 (9.1%)
DEHYDRATION	6/26 (23.1%)		0/33 (0%)
EDEMA	2/26 (7.7%)		6/33 (18.2%)
GOUT	2/26 (7.7%)		0/33 (0%)
HYPERCALCEMIA	0/26 (0%)		3/33 (9.1%)
HYPERGLYCEMIA	4/26 (15.4%)		14/33 (42.4%)
HYPOCALCEMIA	0/26 (0%)		3/33 (9.1%)
HYPOKALEMIA	6/26 (23.1%)		13/33 (39.4%)
HYPONATREMIA	3/26 (11.5%)		6/33 (18.2%)
HYPOPROTEINEMIA	3/26 (11.5%)		15/33 (45.5%)
PERIPHERAL EDEMA	4/26 (15.4%)		10/33 (30.3%)
RESPIRATORY ALKALOSIS	0/26 (0%)		2/33 (6.1%)
SGOT INCREASED	2/26 (7.7%)		7/33 (21.2%)
SGPT INCREASED	2/26 (7.7%)		8/33 (24.2%)
WEIGHT LOSS	2/26 (7.7%)		3/33 (9.1%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	0/26 (0%)		2/33 (6.1%)
MYASTHENIA	0/26 (0%)		5/33 (15.2%)
PATHOLOGICAL FRACTURE	2/26 (7.7%)		0/33 (0%)
Nervous system disorders
ANXIETY	2/26 (7.7%)		3/33 (9.1%)
CONFUSION	0/26 (0%)		2/33 (6.1%)
DEPRESSION	2/26 (7.7%)		2/33 (6.1%)
DIZZINESS	2/26 (7.7%)		4/33 (12.1%)
HYPERTENSION	3/26 (11.5%)		2/33 (6.1%)
INSOMNIA	10/26 (38.5%)		15/33 (45.5%)
NEUROPATHY	4/26 (15.4%)		4/33 (12.1%)
PARESTHESIA	0/26 (0%)		2/33 (6.1%)
URINARY RETENTION	0/26 (0%)		2/33 (6.1%)
VASODILATATION	4/26 (15.4%)		7/33 (21.2%)
Renal and urinary disorders
KIDNEY FUNCTION ABNORMAL	0/26 (0%)		2/33 (6.1%)
URINARY TRACT INFECTION	2/26 (7.7%)		2/33 (6.1%)
Respiratory, thoracic and mediastinal disorders
COUGH INCREASED	10/26 (38.5%)		10/33 (30.3%)
DYSPNEA	13/26 (50%)		13/33 (39.4%)
EPISTAXIS	3/26 (11.5%)		2/33 (6.1%)
HEMOPTYSIS	4/26 (15.4%)		0/33 (0%)
HICCUP	0/26 (0%)		2/33 (6.1%)
HYPOVENTILATION	0/26 (0%)		2/33 (6.1%)
LUNG DISORDER	5/26 (19.2%)		2/33 (6.1%)
LUNG EDEMA	0/26 (0%)		2/33 (6.1%)
PHARYNGITIS	0/26 (0%)		4/33 (12.1%)
PNEUMONIA	2/26 (7.7%)		4/33 (12.1%)
RHINITIS	3/26 (11.5%)		3/33 (9.1%)
SINUSITIS	2/26 (7.7%)		0/33 (0%)
Skin and subcutaneous tissue disorders
ALOPECIA	0/26 (0%)		5/33 (15.2%)
RASH	8/26 (30.8%)		6/33 (18.2%)
SWEATING	0/26 (0%)		7/33 (21.2%)
Vascular disorders
HYPOTENSION	0/26 (0%)		2/33 (6.1%)
PALLOR	0/26 (0%)		2/33 (6.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.