Carboplatin, Paclitaxel, Selenomethionine, and Radiation Therapy in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00526890
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 47
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Selenomethionine may slow the growth of tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with selenomethionine and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well selenomethionine works when given together with carboplatin, paclitaxel, and radiation therapy in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Dietary Supplement: selenomethionine; Drug: carboplatin; Drug: paclitaxel; Other: laboratory biomarker analysis; Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the safety and tolerability of selenomethionine in combination with chemotherapy and radiotherapy in patients with unresectable stage IIIA or IIIB non-small cell lung cancer.

• Determine if the incidence of excessive adverse events, in the form of esophagitis, pneumonitis, and myelosuppression, can be reduced with this regimen.

Secondary

• Estimate response rate, failure-free survival, and overall survival of these patients.

• Correlate selenium levels with degree of observed adverse events.

OUTLINE: This is a multicenter study.

Patients receive oral selenomethionine twice daily for 1 week and then once daily for 6 weeks. Patients also receive paclitaxel IV over 1 hour once weekly and carboplatin IV over 30 minutes once weekly for 6 weeks and undergo radiotherapy 5 days a week for 6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and weekly during treatment and analyzed by absorption spectrophotometry for selenium measurement of drug concentration

After the completion of study treatment, patients are followed periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination With Radiation for Patients With Unresectable Stage III Non-Small Cell Lung Cancer: A Phase II, Multi-Center Trial
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CPSR Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination with Radiation	Dietary Supplement: selenomethionine; Oral Twice daily; Drug: carboplatin; Weekly IV; Drug: paclitaxel; Weekly IV; Other: laboratory biomarker analysis; Correlative Study; Radiation: radiation therapy; Undergoing radiation Therapy

Outcome Measures

Primary Outcome Measures

1. Incidence of Grade 3-4 Esophagitis [During study treatment, up to 6 weeks]

2. Incidence of Grade 3-4 Pneumonitis [During study treatment, up to 6 weeks]

3. Incidence of Grade 3-4 Myelosuppression [During study treatment, up to 6 weeks]

Secondary Outcome Measures

1. Response Rate [1 month post-treatment, then q 3 months x 4]

   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. Failure-free Survival [Post-treatment follow-up every 3 months x4, then per institute standard of practice every 6 months for 2 years, then yearly therafter.]

3. Overall Survival [Post-treatment follow-up every 3 months x4, then per institute standard of practice every 6 months for 2 years, then yearly therafter]

4. Selenium Level by Incidence of SAE [Pre-treatment and every week for 6 weeks prior to chemotherapy.]

   Median Selenium level by Incidence of SAE. Mann-Whitney-Wilcoxon test was used to test the correlation between selenium levels and serious adverse events.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), including any of the following histologic subtypes:

• Squamous cell carcinoma

• Adenocarcinoma (including bronchoalveolar cell carcinoma)

• Large cell anaplastic carcinoma (including giant and clear cell carcinoma)

• Stage IIIA disease OR selected stage IIIB disease

• T1-2, N2 disease OR T3, N2 or T4, N0-N2 disease (if based on tumor closeness to the carina, invasion of the mediastinum, or invasion of the chest wall)

• Contralateral mediastinal disease (N3) allowed if all gross disease can be encompassed in the radiation boost field

• Tumors adjacent to a vertebral body allowed unless there is demonstrable bone invasion

• All gross disease must be able to be encompassed in the radiation boost field

• No direct invasion of a vertebrae body

• Unresectable or inoperable disease

• Measurable disease

• Suitable for radiotherapy, as deemed by the radiation oncologist

• No scalene, supraclavicular, or contralateral hilar node involvement

• Pleural effusion allowed provided it is transudate, cytologically negative, and non-bloody, and, according to the radiation oncologist, the tumor can be encompassed within a reasonable radiation field

• Pleural effusion seen on chest CT scan, but not on chest x-ray, that is too small to tap is allowed

• No exudative, bloody, or cytologically malignant effusions

• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• ANC ≥ 1,500/mm³

• Platelet count ≥ 75,000/mm³

• Total bilirubin ≤ 1.5 mg/dL

• Creatinine normal

• Alkaline phosphatase AND AST or ALT meeting 1 of the following criteria:

• Alkaline phosphatase normal AND AST or ALT ≤ 5 times upper limit of normal (ULN)

• Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN

• Alkaline phosphatase ≤ 5 times ULN AND AST or ALT normal

• Able to swallow oral medications

• No peripheral neuropathy > grade 1

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to selenomethionine or agents formulated with Cremophor EL

• No concurrent uncontrolled illness including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Clinically significant cardiac arrhythmia

• Psychiatric illness or social situations that would limit compliance with study requirements

• No currently "active" second malignancy other than non-melanoma skin cancer

• Patients are considered not to have an "active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse

• Not pregnant

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• At least 2 weeks since prior formal exploratory thoracotomy (N2 node identified making patient ineligible for surgery)

• No prior chemotherapy or radiotherapy for NSCLC

• No prior taxanes or platinum drugs

• No other concurrent investigational agents or anticancer therapy

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent chemotherapy or hormonal therapy, except for the following:

• Steroids administered for adrenal failure or septic shock

• Hormones administered for non-disease-related conditions (e.g., insulin for diabetes)

• Glucocorticosteroids administered as antiemetics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001

Sponsors and Collaborators

• Roswell Park Cancer Institute

Investigators

• Principal Investigator: Jorge Gomez, MD, Roswell Park Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT00526890
• Other Study ID Numbers: CDR0000562780; RPCI-I-65605
• First Posted: Sep 10, 2007
• Last Update Posted: Nov 28, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by Roswell Park Cancer Institute: squamous cell lung cancer; adenocarcinoma of the lung; bronchoalveolar cell lung cancer; large cell lung cancer; stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; adenosquamous cell lung cancer
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Selenium; Paclitaxel; Carboplatin

Study Results

Participant Flow

Arm/Group Title	CPSR
Arm/Group Description	Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination with Radiation
Period Title: Overall Study
STARTED	16
COMPLETED	14
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	CPSR
Arm/Group Description	Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination with Radiation
Overall Participants	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.25 (9.22)
Sex: Female, Male (Count of Participants)
Female	11 68.8%
Male	5 31.3%

Outcome Measures

1. Primary Outcome

Title	Incidence of Grade 3-4 Esophagitis
Time Frame	During study treatment, up to 6 weeks

Outcome Measure Data

Analysis Population Description

Treated with Study Therapy

Arm/Group Title	CPSR
Arm/Group Description	Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination with Radiation
Measure Participants	16
Number (95% Confidence Interval) [percentage of participants]	18.75 117.2%

2. Primary Outcome

Title	Incidence of Grade 3-4 Pneumonitis
Time Frame	During study treatment, up to 6 weeks

Outcome Measure Data

Analysis Population Description

Patients treated with study therapy

Arm/Group Title	CPSR
Arm/Group Description	Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination with Radiation
Measure Participants	16
Number (95% Confidence Interval) [percentage of participants]	0 0%

3. Primary Outcome

Title	Incidence of Grade 3-4 Myelosuppression
Time Frame	During study treatment, up to 6 weeks

Outcome Measure Data

Analysis Population Description

Patients Treated with Study Therapy

Arm/Group Title	CPSR
Arm/Group Description	Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination with Radiation
Measure Participants	16
Number (95% Confidence Interval) [percentage of participants]	12.50 78.1%

4. Secondary Outcome

Title	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	1 month post-treatment, then q 3 months x 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CPSR
Arm/Group Description	Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination with Radiation
Measure Participants	16
Number (95% Confidence Interval) [percentage of patients]	50

5. Secondary Outcome

Title	Failure-free Survival
Time Frame	Post-treatment follow-up every 3 months x4, then per institute standard of practice every 6 months for 2 years, then yearly therafter.

Outcome Measure Data

Analysis Population Description

Patients treated with study therapy

Arm/Group Title	CPSR
Arm/Group Description	Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination with Radiation
Measure Participants	16
Median (95% Confidence Interval) [months]	9.0

6. Secondary Outcome

Title	Overall Survival
Time Frame	Post-treatment follow-up every 3 months x4, then per institute standard of practice every 6 months for 2 years, then yearly therafter

Outcome Measure Data

Analysis Population Description

Patients treated with study therapy

Arm/Group Title	CPSR
Arm/Group Description	Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination with Radiation
Measure Participants	16
Median (95% Confidence Interval) [months]	14.5

7. Secondary Outcome

Title	Selenium Level by Incidence of SAE
Description	Median Selenium level by Incidence of SAE. Mann-Whitney-Wilcoxon test was used to test the correlation between selenium levels and serious adverse events.
Time Frame	Pre-treatment and every week for 6 weeks prior to chemotherapy.

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	CPSR
Arm/Group Description	Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination with Radiation
Measure Participants	16
No SAE	1435.0
SAE	1803.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CPSR
	Comments	Mann-Whitney-Wilcoxon test was used to test the correlation between selenium levels and serious adverse events.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3149
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Arm/Group Title	CPSR
Arm/Group Description	Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination with Radiation
All Cause Mortality
	CPSR
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	CPSR
	Affected / at Risk (%)	# Events
Total	4/16 (25%)
Cardiac disorders
Atrial fibrillation - Grade 2	1/16 (6.3%)	1
Gastrointestinal disorders
Oesophagitis - Grade 3	1/16 (6.3%)	1
Infections and infestations
Urinary tract infection - Grade 3	1/16 (6.3%)	1
Metabolism and nutrition disorders
Hypokalaemia - Grade 4	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	CPSR
	Affected / at Risk (%)	# Events
Total	16/16 (100%)
Blood and lymphatic system disorders
Anaemia - Grade 1	7/16 (43.8%)	9
Anaemia - Grade 2	4/16 (25%)	5
Anaemia - Grade 3	1/16 (6.3%)	1
Leukopenia - Grade 1	8/16 (50%)	8
Leukopenia - Grade 2	6/16 (37.5%)	6
Leukopenia - Grade 3	2/16 (12.5%)	2
Neutropenia - Grade 1	3/16 (18.8%)	3
Neutropenia - Grade 2	2/16 (12.5%)	2
Thrombocytopenia - Grade 1	2/16 (12.5%)	2
Cardiac disorders
Arrhythmia - Grade 1	1/16 (6.3%)	1
Tachycardia - Grade 1	2/16 (12.5%)	2
Ear and labyrinth disorders
Ear pain - Grade 2	1/16 (6.3%)	1
Gastrointestinal disorders
Abdominal pain - Grade 1	1/16 (6.3%)	1
Abdominal pain - Grade 2	1/16 (6.3%)	1
Breath odour - Grade 1	1/16 (6.3%)	1
Chapped lips - Grade 1	1/16 (6.3%)	1
Constipation - Grade 1	5/16 (31.3%)	6
Constipation - Grade 2	2/16 (12.5%)	2
Diarrhoea - Grade 1	1/16 (6.3%)	1
Diarrhoea - Grade 2	1/16 (6.3%)	1
Dyspepsia - Grade 1	2/16 (12.5%)	2
Dyspepsia - Grade 2	1/16 (6.3%)	1
Dysphagia - Grade 1	1/16 (6.3%)	1
Nausea - Grade 1	2/16 (12.5%)	2
Nausea - Grade 2	1/16 (6.3%)	1
Oesophageal pain - Grade 2	1/16 (6.3%)	1
Oesophagitis - Grade 1	5/16 (31.3%)	6
Oesophagitis - Grade 2	9/16 (56.3%)	10
Oesophagitis - Grade 3	2/16 (12.5%)	2
Stomatitis - Grade 3	1/16 (6.3%)	1
General disorders
Chest pain - Grade 1	1/16 (6.3%)	1
Fatigue - Grade 1	6/16 (37.5%)	7
Fatigue - Grade 2	3/16 (18.8%)	4
Fatigue - Grade 3	1/16 (6.3%)	1
Mucosal inflammation - Grade 2	1/16 (6.3%)	1
Oedema peripheral - Grade 1	1/16 (6.3%)	1
Oedema peripheral - Grade 2	1/16 (6.3%)	1
Pain - Grade 1	1/16 (6.3%)	1
Pain - Grade 2	2/16 (12.5%)	2
Pyrexia - Grade 1	1/16 (6.3%)	3
Infections and infestations
Bacterial infection - Grade 2	1/16 (6.3%)	1
Herpes zoster - Grade 2	1/16 (6.3%)	1
Infection - Grade 2	1/16 (6.3%)	1
Lower respiratory tract infection - Grade 1	1/16 (6.3%)	1
Lower respiratory tract infection - Grade 2	1/16 (6.3%)	1
Urinary tract infection - Grade 1	1/16 (6.3%)	1
Urinary tract infection - Grade 2	1/16 (6.3%)	1
Injury, poisoning and procedural complications
Contusion - Grade 1	1/16 (6.3%)	1
Radiation pneumonitis - Grade 1	1/16 (6.3%)	1
Radiation pneumonitis - Grade 2	3/16 (18.8%)	3
Radiation skin injury - Grade 1	1/16 (6.3%)	1
Radiation skin injury - Grade 2	1/16 (6.3%)	1
Thermal burn - Grade 1	2/16 (12.5%)	2
Investigations
Blood alkaline phosphatase increased - Grade 1	1/16 (6.3%)	1
Weight decreased - Grade 1	1/16 (6.3%)	1
Weight decreased - Grade 2	1/16 (6.3%)	1
Metabolism and nutrition disorders
Anorexia - Grade 2	2/16 (12.5%)	2
Decreased appetite - Grade 1	1/16 (6.3%)	1
Dehydration - Grade 3	1/16 (6.3%)	1
Hypercholesterolaemia - Grade 1	1/16 (6.3%)	1
Hyperglycaemia - Grade 1	7/16 (43.8%)	10
Hyperglycaemia - Grade 2	5/16 (31.3%)	7
Hyperglycaemia - Grade 3	6/16 (37.5%)	6
Hyperkalaemia - Grade 1	2/16 (12.5%)	2
Hypernatraemia - Grade 1	1/16 (6.3%)	1
Hypertriglyceridaemia - Grade 1	1/16 (6.3%)	1
Hypoalbuminaemia - Grade 1	1/16 (6.3%)	1
Hypoalbuminaemia - Grade 2	1/16 (6.3%)	1
Hypocalcaemia - Grade 2	1/16 (6.3%)	1
Hypokalaemia - Grade 1	4/16 (25%)	4
Hypokalaemia - Grade 3	1/16 (6.3%)	1
Hypomagnesaemia - Grade 1	2/16 (12.5%)	2
Hyponatraemia - Grade 1	4/16 (25%)	4
Musculoskeletal and connective tissue disorders
Arthralgia - Grade 2	1/16 (6.3%)	1
Back pain - Grade 1	1/16 (6.3%)	1
Limb discomfort - Grade 1	1/16 (6.3%)	1
Muscular weakness - Grade 2	1/16 (6.3%)	1
Musculoskeletal chest pain - Grade 1	1/16 (6.3%)	1
Myalgia - Grade 1	1/16 (6.3%)	1
Nervous system disorders
Dizziness - Grade 1	1/16 (6.3%)	1
Dysgeusia - Grade 1	1/16 (6.3%)	1
Extrapyramidal disorder - Grade 2	1/16 (6.3%)	1
Headache - Grade 2	1/16 (6.3%)	1
Neuropathy peripheral - Grade 1	1/16 (6.3%)	1
Peripheral sensory neuropathy - Grade 1	1/16 (6.3%)	1
Psychiatric disorders
Insomnia - Grade 2	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough - Grade 1	2/16 (12.5%)	3
Dyspnoea - Grade 2	1/16 (6.3%)	1
Haemoptysis - Grade 1	1/16 (6.3%)	1
Hypoxia - Grade 3	1/16 (6.3%)	1
Pharyngolaryngeal pain - Grade 1	1/16 (6.3%)	1
Pleural effusion - Grade 1	1/16 (6.3%)	1
Pleuritic pain - Grade 1	1/16 (6.3%)	1
Productive cough - Grade 2	1/16 (6.3%)	1
Pulmonary embolism - Grade 3	1/16 (6.3%)	1
Rhinorrhoea - Grade 1	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders
Alopecia - Grade 1	1/16 (6.3%)	1
Hyperhidrosis - Grade 1	1/16 (6.3%)	1
Night sweats - Grade 1	2/16 (12.5%)	2
Vascular disorders
Deep vein thrombosis - Grade 3	1/16 (6.3%)	1
Hypotension - Grade 2	1/16 (6.3%)	1
Orthostatic hypotension - Grade 1	1/16 (6.3%)	1
Orthostatic hypotension - Grade 2	1/16 (6.3%)	1
Orthostatic hypotension - Grade 3	1/16 (6.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.