Preoperative Therapy in Patients With Stages IB, II, IIIA, and Selected IIIB Patients With Non-Small Cell Lung Cancer

• Sponsor: SCRI Development Innovations, LLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT00193427
• Collaborator: Aventis Pharmaceuticals (Industry), Eli Lilly and Company (Industry)
• Enrollment: 75
• Location: 1
• Arm: 1
• Duration (Months): 56
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

This trial is designed to study the role of docetaxel/gemcitabine, an active and relatively non-toxic combination in advanced NSCLC. This study will help to better define optimal preoperative regimens for patients with resectable NSCLC. Since both of these drugs are potent radio-sensitizers, the concurrent use with radiation therapy at these weekly doses may produce not only radio-sensitization, but also considerable antitumor efficacy.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: Docetaxel; Drug: Gemcitabine; Drug: Carboplatin; Radiation: Radiation	Phase 2

Detailed Description

Upon determination of eligibility, patients will receive:

Pre-operative

• Docetaxel

• Gemcitabine Post-operative

• Docetaxel

• Carboplatin

• Radiation Therapy

Patients with stage IB and II NSCLC who achieved clear margins will not receive any further therapy. Patients with incomplete resection, resection margins of a T3 tumor that are positive or close, stage IIIA AND IIIB NSCLC or disease judged unresectable after preoperative chemotherapy will receive postoperative treatment

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 of Preoperative (Neo-adjuvant) Therapy in Patients With Stages IB, II, IIIA, and Selected IIIB Patients With Non-Small Cell Lung Cancer
• Study Start Date: Apr 1, 2004
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Intervention Patients with potentially resectable clinical stage IB, II, and selected III NSCLC received gemcitabine 1000 mg/m2 days 1, 8 and docetaxel 30 mg/m2 days 1, 8 every 21 days for 3 cycles. Patients were restaged after treatment and resected 3-6 weeks later. If patients were inoperable, had incomplete resections or N2 disease, docetaxel 20 mg/m2 and carboplatin AUC = 1.5 weekly x 7 and radiation to 63 Gy was administered

Drug: Docetaxel; 30mg/m2 administered on days 1 and 8, 21-cycle days, 3 cycles; Other Names: Taxotere ; Drug: Gemcitabine; 1000 mg/m2 administered by 30-minute IV infusion on day 1 and 8, 21-cycle days, 3 cycles; Other Names: Gemzar ; Drug: Carboplatin; AUC = 1.5 weekly x 7; Other Names: Paraplatin ; Radiation: Radiation; To 63 Gy

Outcome Measures

Primary Outcome Measures

1. Pathologic Complete Response Rate [18 months]

   A pathological complete response (pCR) was defined as having no residual cancer at the primary site or in regional lymph nodes on pathologic review.

Secondary Outcome Measures

1. Progression Free Survival (PFS) [19 months]

   Progression-free survival was calculated as the elapsed time between the date of study registration and the date of recurrence or death from any cause.

2. Overall Response Rate (ORR) [18 months]

   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.

3. Overall Survival (OS) [18 months]

   Overall survival was calculated as the elapsed time bewteen date of study registration and 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:

To be included in this study, you must meet the following criteria:

• Histologically confirmed non-small cell lung cancer

• Must be operable candidate

• Clinical stage IB, II, and select III non-small cell lung cancer are eligible

• Measurable or evaluable disease

• Able to perform activities of daily living with minimal assistance

• Must be > 18 years of age

• Adequate bone marrow, liver or kidney

• No previous chemotherapy or radiation therapy for non-small cell lung cancer

• Moderate to severe peripheral neuropathy

• Understand the nature of this study and give written informed consent.

Exclusion Criteria:

You cannot participate in this study if any of the following apply to you:

• Stage IV disease

• History of prior malignancy within five years

• Women who are pregnant or breast-feeding

Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37023

Sponsors and Collaborators

• SCRI Development Innovations, LLC
• Aventis Pharmaceuticals
• Eli Lilly and Company

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT00193427
• Other Study ID Numbers: SCRI LUN 76
• First Posted: Sep 19, 2005
• Last Update Posted: Mar 3, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Lung Neoplasms; Gemcitabine; Carboplatin; Docetaxel

Study Results

Participant Flow

Arm/Group Title	Intervention
Arm/Group Description	Patients with potentially resectable clinical stage IB, II, and selected III NSCLC received gemcitabine 1000 mg/m2 days 1, 8 and docetaxel 30 mg/m2 days 1, 8 every 21 days for 3 cycles. Patients were restaged after treatment and resected 3-6 weeks later. If patients were inoperable, had incomplete resections or N2 disease, docetaxel 20 mg/m2 and carboplatin AUC = 1.5 weekly x 7 and radiation to 63 Gy was administered
Period Title: Overall Study
STARTED	75
COMPLETED	26
NOT COMPLETED	49

Baseline Characteristics

Arm/Group Title	Intervention
Arm/Group Description	Patients with potentially resectable clinical stage IB, II, and selected III NSCLC received gemcitabine 1000 mg/m2 days 1, 8 and docetaxel 30 mg/m2 days 1, 8 every 21 days for 3 cycles. Patients were restaged after treatment and resected 3-6 weeks later. If patients were inoperable, had incomplete resections or N2 disease, docetaxel 20 mg/m2 and carboplatin AUC = 1.5 weekly x 7 and radiation to 63 Gy was administered
Overall Participants	75
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62
Sex: Female, Male (Count of Participants)
Female	28 37.3%
Male	47 62.7%
Region of Enrollment (participants) [Number]
United States	75 100%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response Rate
Description	A pathological complete response (pCR) was defined as having no residual cancer at the primary site or in regional lymph nodes on pathologic review.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All patients who underwent a thoracotomy were assigned a pathologic response category.

Arm/Group Title	Intervention
Arm/Group Description	Patients with potentially resectable clinical stage IB, II, and selected III NSCLC received gemcitabine 1000 mg/m2 days 1, 8 and docetaxel 30 mg/m2 days 1, 8 every 21 days for 3 cycles. Patients were restaged after treatment and resected 3-6 weeks later. If patients were inoperable, had incomplete resections or N2 disease, docetaxel 20 mg/m2 and carboplatin AUC = 1.5 weekly x 7 and radiation to 63 Gy was administered
Measure Participants	38
Number [Percentage of participants]	0 0%

2. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Progression-free survival was calculated as the elapsed time between the date of study registration and the date of recurrence or death from any cause.
Time Frame	19 months

Outcome Measure Data

Analysis Population Description

All patients were assessed for progression free survival after a median follow up of 19 months.

Arm/Group Title	Intervention
Arm/Group Description	Patients with potentially resectable clinical stage IB, II, and selected III NSCLC received gemcitabine 1000 mg/m2 days 1, 8 and docetaxel 30 mg/m2 days 1, 8 every 21 days for 3 cycles. Patients were restaged after treatment and resected 3-6 weeks later. If patients were inoperable, had incomplete resections or N2 disease, docetaxel 20 mg/m2 and carboplatin AUC = 1.5 weekly x 7 and radiation to 63 Gy was administered.
Measure Participants	67
Median (95% Confidence Interval) [Months]	9.9

3. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	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.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Patients who were assessable after completion of 9 weeks of treatment were evaluated and assigned a response category.

Arm/Group Title	Intervention
Arm/Group Description	Patients with potentially resectable clinical stage IB, II, and selected III NSCLC received gemcitabine 1000 mg/m2 days 1, 8 and docetaxel 30 mg/m2 days 1, 8 every 21 days for 3 cycles. Patients were restaged after treatment and resected 3-6 weeks later. If patients were inoperable, had incomplete resections or N2 disease, docetaxel 20 mg/m2 and carboplatin AUC = 1.5 weekly x 7 and radiation to 63 Gy was administered
Measure Participants	67
Number [percentage of participants]	30 40%

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival was calculated as the elapsed time bewteen date of study registration and the date of death.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All patients were assessed for overall survival after a median follow-up of 19 months.

Arm/Group Title	Intervention
Arm/Group Description	Patients with potentially resectable clinical stage IB, II, and selected III NSCLC received gemcitabine 1000 mg/m2 days 1, 8 and docetaxel 30 mg/m2 days 1, 8 every 21 days for 3 cycles. Patients were restaged after treatment and resected 3-6 weeks later. If patients were inoperable, had incomplete resections or N2 disease, docetaxel 20 mg/m2 and carboplatin AUC = 1.5 weekly x 7 and radiation to 63 Gy was administered
Measure Participants	67
Median (95% Confidence Interval) [Months]	18

Adverse Events

Arm/Group Title	Intervention
Arm/Group Description	Patients with potentially resectable clinical stage IB, II, and selected III NSCLC received gemcitabine 1000 mg/m2 days 1, 8 and docetaxel 30 mg/m2 days 1, 8 every 21 days for 3 cycles. Patients were restaged after treatment and resected 3-6 weeks later. If patients were inoperable, had incomplete resections or N2 disease, docetaxel 20 mg/m2 and carboplatin AUC = 1.5 weekly x 7 and radiation to 63 Gy was administered
All Cause Mortality
	Intervention
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Intervention
	Affected / at Risk (%)	# Events
Total	39/75 (52%)
Blood and lymphatic system disorders
Edema	1/75 (1.3%)
Cardiac disorders
Cardiac General - Other (Coronary Artery Disease)	1/75 (1.3%)
Cardiac ischemia/infarction	1/75 (1.3%)
Cardiopulmonary arrest	1/75 (1.3%)
Gastrointestinal disorders
Anorexia	1/75 (1.3%)
Colitis	2/75 (2.7%)
Dehydration	2/75 (2.7%)
Dysphagia	1/75 (1.3%)
Obstruction, GI - Bowel NOS	1/75 (1.3%)
General disorders
Death not associated with CTCAE term (Death NOS)	2/75 (2.7%)
Death not associated with CTCAE term (Disease Progression NOS)	4/75 (5.3%)
Infections and infestations
Febrile neutropenia	2/75 (2.7%)
Infection - Other (bronchitis)	1/75 (1.3%)
Infection with normal ANC - Lung (pnemonia)	1/75 (1.3%)
Infection with unknown ANC - Lung (pnemonia)	3/75 (4%)
Nervous system disorders
CNS cerebrovascular ischemia	1/75 (1.3%)
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome (ARDS)	1/75 (1.3%)
Dyspnea	2/75 (2.7%)
Hemorrhage, pulmonary/upper respiratory	1/75 (1.3%)
Hypoxia	1/75 (1.3%)
Pulmonary/Upper Respiratory - Other (Acute respiratory failure)	2/75 (2.7%)
Pulmonary/Upper Respiratory - Other (Chronic Obstructive Pulmonary Disease)	4/75 (5.3%)
Surgical and medical procedures
Intra-operative injury - Heart	1/75 (1.3%)
Vascular disorders
Thrombosis/thrombus/embolism	2/75 (2.7%)
Other (Not Including Serious) Adverse Events
	Intervention
	Affected / at Risk (%)	# Events
Total	75/75 (100%)
Blood and lymphatic system disorders
Hemoglobin	50/75 (66.7%)
Edema	11/75 (14.7%)
Hemorrhage, pulmonary/upper respiratory	5/75 (6.7%)
Leukocytes	46/75 (61.3%)
Neutrophils	39/75 (52%)
Platelets	51/75 (68%)
Cardiac disorders
Hypotension	5/75 (6.7%)
Gastrointestinal disorders
Anorexia	32/75 (42.7%)
Constipation	22/75 (29.3%)
Dehydration	8/75 (10.7%)
dysphagia	7/75 (9.3%)
Esophagitis	4/75 (5.3%)
Mucositis	10/75 (13.3%)
Nausea	36/75 (48%)
Radiation esophagitis	14/75 (18.7%)
Taste Alteration	7/75 (9.3%)
Vomiting	12/75 (16%)
General disorders
Fatigue	72/75 (96%)
Fever	5/75 (6.7%)
Insomnia	11/75 (14.7%)
Pain (NOS)	28/75 (37.3%)
Weight Loss	4/75 (5.3%)
Infections and infestations
Infection	27/75 (36%)
Metabolism and nutrition disorders
Hyperglycemia	9/75 (12%)
Musculoskeletal and connective tissue disorders
Pain - joint	8/75 (10.7%)
Pain - muscles	5/75 (6.7%)
Nervous system disorders
Neuropathy - sensory	6/75 (8%)
Psychiatric disorders
Mood alteration - anxiety	6/75 (8%)
Respiratory, thoracic and mediastinal disorders
Cough	7/75 (9.3%)
Dyspnea	4/75 (5.3%)
Pulmonary Symptoms	28/75 (37.3%)
Skin and subcutaneous tissue disorders
Alopecia	24/75 (32%)
Skin toxicity	22/75 (29.3%)

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.