Ph II Adjuvant Carboplatin/Docetaxel in Curatively Resected Stage I-IIIA NSCLC

• Sponsor: UNC Lineberger Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00280735
• Collaborator: Aventis Pharmaceuticals (Industry)
• Enrollment: 75
• Location: 1
• Arm: 1
• Actual Duration (Months): 86
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving carboplatin together with docetaxel after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving carboplatin together with docetaxel works in treating patients with stage I, stage II, or stage III non-small cell lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: carboplatin; Drug: docetaxel	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Evaluate the feasibility of adjuvant carboplatin and docetaxel in patients with resected stage I, II, or IIIA non-small cell lung cancer.

Secondary

• Determine the toxicity of this regimen in these patients.

• Determine the survival patterns of patients treated with this regimen.

• Assess the patterns of recurrence in patients treated with this regimen.

OUTLINE: Patients receive carboplatin IV on day 1 and docetaxel IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial Exploring the Feasibility of Adjuvant Carboplatin/Docetaxel in Curatively Resected Stage I-IIIA Non-Small Cell Lung Cancer
• Actual Study Start Date: May 1, 2004
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Other: Single Arm Trial adjuvant carboplatin plus docetaxel carboplatin area under curve (AUC) = 6 IV on day 1 every 3 weeks for 4 cycles docetaxel 75 mg/m² IV on day 1 every 3 weeks for 4 cycles	Drug: carboplatin; Carboplatin will be given intravenously,once,every 3 weeks. The carboplatin area under curve (AUC) dose will be calculated using the Calvert Equation 19 as follows: Carboplatin dose (mg) = 6x (GFR + 25); Other Names: paraplatin ; Drug: docetaxel; 75 mg/m² intravenously, once, every 3 weeks; Other Names: Taxotere

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Completed Four Cycles of the Carboplatin/Docetaxel Regimen [12 weeks from initiating adjuvant therapy]

   Feasibility was based on the percentage of patients completing four cycles of the carboplatin/docetaxel regimen to a high fraction of patients with curatively resected stage IIIIA non-small cell lung cancer within 12 weeks.

Secondary Outcome Measures

1. Patterns of Recurrence in Patients Treated With This Regimen [Up to 5 years]

   Patterns were assessed with a staging chest computerized tomography (CT), bone or positron emission tomography (PET) scan and brain magnetic resonance imaging (MRI)/CT scan at recurrence.

2. Toxicity in Patients Treated With This Regimen [Day 1 of treatment to 30 days after treatment discontinuation]

   Safety determinations are based on the rate of drug-related adverse events (AEs) reported based upon the toxicity as measured by the NCI Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0).

3. Progression Free Survival [The time between the start of treatment to disease progression or death or the date of last contact, measured up to 18 months]

   Relapse-free survival rate at 18 months. Patients were determined to have progression either by radiographic and/or pathological assessment by local physician per local standard of care monitoring for disease recurrence.

4. Overall Survival [The time between the start of treatment to disease progression or death or the date of last contact, measured up to 18 months]

   Overall survival rate at 18 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically confirmed non-small cell lung cancer

• Stage I-IIIA disease

• Must have undergone a complete resection

• Must begin adjuvant chemotherapy within 8 weeks of surgical resection

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Absolute neutrophil count ≥ 1,500/mm^3

• Hemoglobin ≥ 8.0 g/dL

• Platelet count ≥ 100,000/mm^3

• Serum creatinine normal OR creatinine clearance ≥ 40 mL/min

• Bilirubin normal

• Alkaline phosphatase (AP), Aspartate aminotransferase (AST), and Alanine transaminase (ALT) must meet 1 of the following criteria:

• AP normal AND AST and ALT ≤ 5 times upper limit of normal (ULN)

• AP ≤ 2.5 times ULN AND AST and ALT ≤ 1.5 times ULN

• AP ≤ 5 times ULN AND AST and ALT normal

• Negative pregnancy test

• Fertile patients must use effective contraception during and for at least 3 months after study therapy

Exclusion criteria:

• Patients with a history of severe hypersensitivity to docetaxel or polysorbate 80 are excluded.

• Women who are currently or planning to breast feed.

• Those with peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

• 2-8 weeks since prior surgery and recovered

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of North Carolina Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• UNC Lineberger Comprehensive Cancer Center
• Aventis Pharmaceuticals

Investigators

• Principal Investigator: Mark A. Socinski, MD, Florida Hospital Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UNC Lineberger Comprehensive Cancer Center

Publications

None provided.

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00280735
• Other Study ID Numbers: LCCC 0320
• First Posted: Jan 23, 2006
• Last Update Posted: Jul 11, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by UNC Lineberger Comprehensive Cancer Center: stage I non-small cell lung cancer; stage II non-small cell lung cancer; stage IIIA non-small cell lung cancer
• Additional relevant MeSH terms: Lung Neoplasms; Carboplatin; Docetaxel

Study Results

Participant Flow

Pre-assignment Detail	Of the 75 participants screened for eligibility, 72 went on to treatment and 3 participants withdrew consent prior to treatment.

Arm/Group Title	Single Arm Trial
Arm/Group Description	adjuvant carboplatin plus docetaxel carboplatin area under curve (AUC) = 6 IV on day 1 every 3 weeks for 4 cycles docetaxel 75 mg/m² IV on day 1 every 3 weeks for 4 cycles carboplatin: Carboplatin will be given intravenously,once,every 3 weeks. The carboplatin area under curve (AUC) dose will be calculated using the Calvert Equation 19 as follows: Carboplatin dose (mg) = 6x (GFR + 25) docetaxel: 75 mg/m² intravenously, once, every 3 weeks
Period Title: Overall Study
STARTED	75
Received Treatment	72
Received Adequate Exposure	57
COMPLETED	57
NOT COMPLETED	18

Baseline Characteristics

Arm/Group Title	Single Arm Trial
Arm/Group Description	adjuvant carboplatin plus docetaxel carboplatin area under curve (AUC) = 6 IV on day 1 every 3 weeks for 4 cycles docetaxel 75 mg/m² IV on day 1 every 3 weeks for 4 cycles carboplatin: Carboplatin will be given intravenously,once,every 3 weeks. The carboplatin area under curve (AUC) dose will be calculated using the Calvert Equation 19 as follows: Carboplatin dose (mg) = 6x (GFR + 25) docetaxel: 75 mg/m² intravenously, once, every 3 weeks
Overall Participants	72
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	48 66.7%
Male	24 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 2.8%
Not Hispanic or Latino	68 94.4%
Unknown or Not Reported	2 2.8%
Race/Ethnicity, Customized (Count of Participants)
White	60 83.3%
African American	7 9.7%
Latino	2 2.8%
Asian	1 1.4%
Unknown or Not Reported	2 2.8%
Region of Enrollment (participants) [Number]
United States	72 100%
Eastern Cooperative Oncology Group (ECOG) Performance status (Count of Participants)
0	28 38.9%
1	43 59.7%
2	1 1.4%
Stage (Count of Participants)
Stage I	29 40.3%
Stage II	26 36.1%
Stage IIIA	16 22.2%
Stage IIIB	1 1.4%
Histology (Count of Participants)
Adenocarcinoma	32 44.4%
Squamous cell carcinoma	30 41.7%
Non-small cell-not otherwise specified	7 9.7%
Large cell carcinoma	3 4.2%
Type of surgery (Count of Participants)
Wedge resection	2 2.8%
Lobectomy	52 72.2%
Bi-lobectomy	7 9.7%
Pneumonectomy	11 15.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Completed Four Cycles of the Carboplatin/Docetaxel Regimen
Description	Feasibility was based on the percentage of patients completing four cycles of the carboplatin/docetaxel regimen to a high fraction of patients with curatively resected stage IIIIA non-small cell lung cancer within 12 weeks.
Time Frame	12 weeks from initiating adjuvant therapy

Outcome Measure Data

Analysis Population Description

Patients assigned to treatment

Arm/Group Title	Single Arm Trial
Arm/Group Description	adjuvant carboplatin plus docetaxel carboplatin area under curve (AUC) = 6 IV on day 1 every 3 weeks for 4 cycles docetaxel 75 mg/m² IV on day 1 every 3 weeks for 4 cycles carboplatin: Carboplatin will be given intravenously,once,every 3 weeks. The carboplatin area under curve (AUC) dose will be calculated using the Calvert Equation 19 as follows: Carboplatin dose (mg) = 6x (GFR + 25) docetaxel: 75 mg/m² intravenously, once, every 3 weeks
Measure Participants	72
Count of Participants [Participants]	57 79.2%

2. Secondary Outcome

Title	Patterns of Recurrence in Patients Treated With This Regimen
Description	Patterns were assessed with a staging chest computerized tomography (CT), bone or positron emission tomography (PET) scan and brain magnetic resonance imaging (MRI)/CT scan at recurrence.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Trial
Arm/Group Description	Patients who relapsed
Measure Participants	19
intrathoracic relapse	4 5.6%
intrathoracic and distant relapse	5 6.9%
distant relapse only without brain	2 2.8%
distant relapse within the brain	8 11.1%

3. Secondary Outcome

Title	Toxicity in Patients Treated With This Regimen
Description	Safety determinations are based on the rate of drug-related adverse events (AEs) reported based upon the toxicity as measured by the NCI Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0).
Time Frame	Day 1 of treatment to 30 days after treatment discontinuation

Outcome Measure Data

Analysis Population Description

Patients receiving treatment

Arm/Group Title	Grade 3 %	Grade 4 %	Grade 3/4 %
Arm/Group Description	Percentage of patients receiving treatment who developed this toxicity	Percentage of patients receiving treatment who developed this toxicity	Percentage of patients receiving treatment who developed this toxicity
Measure Participants	72	72	72
Neutropenia	24 33.3%	42 NaN	65 NaN
Thrombocytopenia	1 1.4%	0 NaN	1 NaN
Febrile Neutorpenia	3 4.2%	8 NaN	11 NaN
Nausea	1 1.4%	0 NaN	1 NaN
Vomiting	1 1.4%	0 NaN	1 NaN
Diarrhea	3 4.2%	0 NaN	3 NaN
Infusional reactions	4 5.6%	0 NaN	4 NaN
Dehydration	1 1.4%	0 NaN	1 NaN
Fatigue/asthenia	5.5 7.6%	0 NaN	5.5 NaN
Syncope	5.5 7.6%	0 NaN	5.5 NaN
Arrythmia	0 0%	1 NaN	1 NaN
Proteinuria	0 0%	1 NaN	1 NaN
Infection	0 0%	3 NaN	3 NaN
Dyspnea	0 0%	1 NaN	1 NaN

4. Secondary Outcome

Title	Progression Free Survival
Description	Relapse-free survival rate at 18 months. Patients were determined to have progression either by radiographic and/or pathological assessment by local physician per local standard of care monitoring for disease recurrence.
Time Frame	The time between the start of treatment to disease progression or death or the date of last contact, measured up to 18 months

Outcome Measure Data

Analysis Population Description

Participants receiving treatment

Arm/Group Title	Single Arm Trial
Arm/Group Description	adjuvant carboplatin plus docetaxel carboplatin area under curve (AUC) = 6 IV on day 1 every 3 weeks for 4 cycles docetaxel 75 mg/m² IV on day 1 every 3 weeks for 4 cycles carboplatin: Carboplatin will be given intravenously,once,every 3 weeks. The carboplatin area under curve (AUC) dose will be calculated using the Calvert Equation 19 as follows: Carboplatin dose (mg) = 6x (GFR + 25) docetaxel: 75 mg/m² intravenously, once, every 3 weeks
Measure Participants	72
Number [percentage of participants]	86 119.4%

5. Secondary Outcome

Title	Overall Survival
Description	Overall survival rate at 18 months.
Time Frame	The time between the start of treatment to disease progression or death or the date of last contact, measured up to 18 months

Outcome Measure Data

Analysis Population Description

Participants receiving treatment

Arm/Group Title	Single Arm Trial
Arm/Group Description	adjuvant carboplatin plus docetaxel carboplatin area under curve (AUC) = 6 IV on day 1 every 3 weeks for 4 cycles docetaxel 75 mg/m² IV on day 1 every 3 weeks for 4 cycles carboplatin: Carboplatin will be given intravenously,once,every 3 weeks. The carboplatin area under curve (AUC) dose will be calculated using the Calvert Equation 19 as follows: Carboplatin dose (mg) = 6x (GFR + 25) docetaxel: 75 mg/m² intravenously, once, every 3 weeks
Measure Participants	72
Number [percentage of participants]	86 119.4%

Adverse Events

Time Frame	30 days following cessation of treatment
Arm/Group Title	Single Arm Trial
Arm/Group Description	adjuvant carboplatin plus docetaxel carboplatin area under curve (AUC) = 6 IV on day 1 every 3 weeks for 4 cycles docetaxel 75 mg/m² IV on day 1 every 3 weeks for 4 cycles carboplatin: Carboplatin will be given intravenously,once,every 3 weeks. The carboplatin area under curve (AUC) dose will be calculated using the Calvert Equation 19 as follows: Carboplatin dose (mg) = 6x (GFR + 25) docetaxel: 75 mg/m² intravenously, once, every 3 weeks
All Cause Mortality
	Single Arm Trial
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Single Arm Trial
	Affected / at Risk (%)	# Events
Total	19/72 (26.4%)
Blood and lymphatic system disorders
Febrile neutropenia	8/72 (11.1%)	9
Cardiac disorders
Cardiac ischemia/infarction	2/72 (2.8%)	2
Supraventricular and nodal arrhythmia - Atrial fibrillation	1/72 (1.4%)	1
Supraventricular and nodal arrhythmia - Supraventricular arrhythmia not otherwise specified (NOS)	1/72 (1.4%)	1
Gastrointestinal disorders
Diarrhea	3/72 (4.2%)	3
Nausea	2/72 (2.8%)	2
Vomiting	2/72 (2.8%)	2
Infections and infestations
Infections, Other (Specify, _Neutropenic sepsis)	1/72 (1.4%)	1
Investigations
Neutrophils/granulocytes (ANC/AGC)	6/72 (8.3%)	8
Leukocytes (total WBC)	1/72 (1.4%)	1
Metabolism and nutrition disorders
Dehydration	2/72 (2.8%)	2
Glucose, serum-high (hyperglycemia)	1/72 (1.4%)	1
Nervous system disorders
Syncope (fainting)	2/72 (2.8%)	3
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/72 (1.4%)	1
Vascular disorders
Hypotension	1/72 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Single Arm Trial
	Affected / at Risk (%)	# Events
Total	63/72 (87.5%)
Blood and lymphatic system disorders
Hemoglobin	4/72 (5.6%)
Febrile neutropenia	1/72 (1.4%)
Cardiac disorders
Supraventricular and nodal arrhythmia - Supraventricular arrhythmia NOS	1/72 (1.4%)
Cardiac ischemia/infarction	3/72 (4.2%)
Eye disorders
Dry eye syndrome	1/72 (1.4%)
Gastrointestinal disorders
Constipation	1/72 (1.4%)
Diarrhea	9/72 (12.5%)
Heartburn/dyspepsia	5/72 (6.9%)
Mucositis/stomatitis (functional/symptomatic) - Oral cavity	2/72 (2.8%)
Nausea	13/72 (18.1%)
Ulcer, GI - Stomach	1/72 (1.4%)
Vomiting	2/72 (2.8%)
General disorders
Constitutional Symptoms - Other (Specify- Weakness)	1/72 (1.4%)
Fatigue (asthenia, lethargy, malaise)	15/72 (20.8%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	1/72 (1.4%)
Edema: limb	3/72 (4.2%)
Pain -Chest	3/72 (4.2%)
Pain - Other (Specify, _Thoracotomy site)	2/72 (2.8%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	6/72 (8.3%)
Investigations
Leukocytes (total WBC)	4/72 (5.6%)
Neutrophils/granulocytes (ANC/AGC)	42/72 (58.3%)
Platelets	1/72 (1.4%)
ALT, SGPT (serum glutamic pyruvic transaminase)	1/72 (1.4%)
AST, SGOT(serum glutamic oxaloacetic transaminase)	1/72 (1.4%)
Metabolism and nutrition disorders
Anorexia	4/72 (5.6%)
Dehydration	2/72 (2.8%)
Albumin, serum-low (hypoalbuminemia)	1/72 (1.4%)
Calcium, serum-low (hypocalcemia)	1/72 (1.4%)
Glucose, serum-high (hyperglycemia)	2/72 (2.8%)
Magnesium, serum-low (hypomagnesemia)	2/72 (2.8%)
Potassium, serum-high (hyperkalemia)	1/72 (1.4%)
Potassium, serum-low (hypokalemia)	1/72 (1.4%)
Sodium, serum-low (hyponatremia)	1/72 (1.4%)
Musculoskeletal and connective tissue disorders
Pain - Back	2/72 (2.8%)
Pain - bone	3/72 (4.2%)
Pain - Joint	3/72 (4.2%)
Pain - Muscle	4/72 (5.6%)
Nervous system disorders
Taste alteration (dysgeusia)	4/72 (5.6%)
Dizziness	1/72 (1.4%)
Neuropathy: motor	1/72 (1.4%)
Neuropathy: sensory	3/72 (4.2%)
Syncope (fainting)	1/72 (1.4%)
Psychiatric disorders
Insomnia	3/72 (4.2%)
Mood alteration - Anxiety	1/72 (1.4%)
Renal and urinary disorders
Proteinuria	1/72 (1.4%)
Renal/Genitourinary - Other (Specify, __UTI)	1/72 (1.4%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	2/72 (2.8%)
Cough	4/72 (5.6%)
Dyspnea (shortness of breath)	5/72 (6.9%)
Hiccoughs (hiccups, singultus)	1/72 (1.4%)
Pulmonary/Upper Respiratory - Other (Specify, _paranasal sinus reaction; runny nose/chills)	2/72 (2.8%)
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	1/72 (1.4%)
Skin and subcutaneous tissue disorders
Dry skin	2/72 (2.8%)
Hair loss/alopecia (scalp or body)	18/72 (25%)
Rash/desquamation	1/72 (1.4%)
Vascular disorders
Flushing	3/72 (4.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.