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

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

Status
Terminated
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00526890
Enrollment
16
Registered
2007-09-10
Start date
2006-10-31
Completion date
2010-09-30
Last updated
2017-11-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lung Cancer

Keywords

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

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.

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.

Interventions

DIETARY_SUPPLEMENTselenomethionine

Oral Twice daily

DRUGcarboplatin

Weekly IV

DRUGpaclitaxel

Weekly IV

OTHERlaboratory biomarker analysis

Correlative Study

RADIATIONradiation therapy

Undergoing radiation Therapy

Sponsors

Roswell Park Cancer Institute
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No

Inclusion criteria

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

Design outcomes

Primary

MeasureTime frame
Incidence of Grade 3-4 EsophagitisDuring study treatment, up to 6 weeks
Incidence of Grade 3-4 PneumonitisDuring study treatment, up to 6 weeks
Incidence of Grade 3-4 MyelosuppressionDuring study treatment, up to 6 weeks

Secondary

MeasureTime frameDescription
Response Rate1 month post-treatment, then q 3 months x 4Per 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.
Selenium Level by Incidence of SAEPre-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.
Failure-free SurvivalPost-treatment follow-up every 3 months x4, then per institute standard of practice every 6 months for 2 years, then yearly therafter.
Overall SurvivalPost-treatment follow-up every 3 months x4, then per institute standard of practice every 6 months for 2 years, then yearly therafter

Countries

United States

Participant flow

Participants by arm

ArmCount
CPSR
Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination with Radiation
16
Total16

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyAdverse Event2

Baseline characteristics

CharacteristicCPSR
Age, Continuous63.25 years
STANDARD_DEVIATION 9.22
Sex: Female, Male
Female
11 Participants
Sex: Female, Male
Male
5 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
16 / 16
serious
Total, serious adverse events
4 / 16

Outcome results

Primary

Incidence of Grade 3-4 Esophagitis

Time frame: During study treatment, up to 6 weeks

Population: Treated with Study Therapy

ArmMeasureValue (NUMBER)
CPSRIncidence of Grade 3-4 Esophagitis18.75 percentage of participants
Primary

Incidence of Grade 3-4 Myelosuppression

Time frame: During study treatment, up to 6 weeks

Population: Patients Treated with Study Therapy

ArmMeasureValue (NUMBER)
CPSRIncidence of Grade 3-4 Myelosuppression12.50 percentage of participants
Primary

Incidence of Grade 3-4 Pneumonitis

Time frame: During study treatment, up to 6 weeks

Population: Patients treated with study therapy

ArmMeasureValue (NUMBER)
CPSRIncidence of Grade 3-4 Pneumonitis0 percentage of participants
Secondary

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.

Population: Patients treated with study therapy

ArmMeasureValue (MEDIAN)
CPSRFailure-free Survival9.0 months
Secondary

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

Population: Patients treated with study therapy

ArmMeasureValue (MEDIAN)
CPSROverall Survival14.5 months
Secondary

Response Rate

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

ArmMeasureValue (NUMBER)
CPSRResponse Rate50 percentage of patients
Secondary

Selenium Level by Incidence of SAE

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.

Population: All treated and eligible patients

ArmMeasureGroupValue (MEDIAN)
CPSRSelenium Level by Incidence of SAENo SAE1435.0 ng/mL
CPSRSelenium Level by Incidence of SAESAE1803.6 ng/mL
Comparison: Mann-Whitney-Wilcoxon test was used to test the correlation between selenium levels and serious adverse events.p-value: 0.3149Wilcoxon (Mann-Whitney)

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026