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Platinum Doublet Chemotherapy and Proton Beam Radiation Therapy in Treating Patients With Stage II-III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

Primary Purpose

Recurrent Lung Non-Small Cell Carcinoma, Stage II Lung Non-Small Cell Cancer AJCC v7, Stage IIA Lung Non-Small Cell Carcinoma AJCC v7

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Carboplatin
Cisplatin
Etoposide
Paclitaxel
Pemetrexed
Proton Beam Radiation Therapy
Quality-of-Life Assessment
Questionnaire Administration
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Lung Non-Small Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histological confirmation of non-small cell lung cancer
  • Forced Expiratory volume in 1 second (FEV1)>1.0 L

  • Unresectable stage 2-3 Non-small cell lung cancer (based on CT/positron emission tomography (PET), MRI or CT of brain, and Physical exam).

    • Eligible if recurrence after surgery and now has the equivalent stage 2-3 NSCLC OR had sub totally resected stage 2-3 NSCLC.

  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
  • Negative pregnancy test done ≤7 days prior to registration, for women of childbearing potential only.

  • The following laboratory values in specified ranges:

    • White blood cell count (WBC) ≥3.0 x 109/L,
    • Absolute neutrophil count (ANC) ≥1.5 x 109/L,
    • Hgb ≥9g/dl
    • Plts >100 x 109/L
    • Serum creatinine<1.5 times upper limit of normal (ULN)
    • Serum bilirubin <1.5 times upper limit of normal (ULN)
  • Provide informed written consent.
  • Willing to return to enrolling institution for follow-up for a minimum of 1 year.
  • Ability to undergo potentially curative chemotherapy plus radiotherapy

Exclusion Criteria:

  • Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
  • Weight loss of >10% in the past 6 months
  • Distant metastases (M1 disease)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, lupus, Usual interstitial pneumonitis (UIP), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Receiving any investigational agent, that would be considered as a treatment for the primary neoplasm.
  • Other active malignancy ≤3 years prior to registration. EXCEPTIONS: treated non-melanotic skin cancer, carcinoma-in-situ of the cervix, treated Stage 1-2, Gleason 7 or less, prostate cancer with a stable or undetectable prostate specific antigen (PSA) level, treated stage 1 breast cancer which is controlled and for which the patient received no thoracic radiotherapy (RT).
  • History of myocardial infarction ≤6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
  • Received chemotherapy for lung cancer within 6 months of registration.
  • Previous chest radiotherapy.

Sites / Locations

  • Mayo Clinic in Arizona
  • Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A (platinum doublet chemotherapy, lower dose PBT)

Arm C (platinum doublet chemotherapy, higher dose PBT)

Arm Description

Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo lower dose proton beam radiation therapy daily for a total of 60 Gy for up to 30 weekdays in the absence of disease progression or unacceptable toxicity.

Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo higher dose proton beam radiation therapy daily for a total of 72 Gy for up to 36 weekdays in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Progression free survival (PFS)
A Cox proportional hazards model stratified by stratification factors will be used to model PFS as a function of dose to test for an overall dose effect (a one-sided p-value < 0.10 will be considered as significant evidence of a dose effect). Subsequently, separate Cox models stratified by stratification factors will compare PFS between 72 Gy and 60 Gy (for each, a one-sided p-value < 0.10 will be considered as significant evidence of superiority). Kaplan Meier estimates and curves by dose level will also be generated

Secondary Outcome Measures

Overall survival (OS)
Will be modeled using Cox models. Kaplan-Meier estimates and curves by dose level will also be generated. OS will again be analyzed as exploratory analysis after 50 deaths per primary pairwise comparison have occurred or after all patients have completed follow-up (whichever occurs first).
Incidence of adverse events
Graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns by dose level (60, 72 Gy). Additionally, the relationship of the adverse event(s) to dose level will be taken into consideration.
Local-regional failure
Defined as the time from randomization to the earliest date of documentation of local recurrence. The cumulative incidence of local failure will be estimated using Gray's methodology and compared across dose levels using Fine-Gray quadratic regression (with death as a competing risk).
Distant metastasis
Defined as the time from randomization to the earliest date of documentation of distant metastasis. The cumulative incidence of distant metastasis will be estimated using Gray's methodology and compared across dose levels using Fine-Gray quadratic regression (with death as a competing risk).

Full Information

First Posted
April 25, 2017
Last Updated
July 3, 2023
Sponsor
Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT03132532
Brief Title
Platinum Doublet Chemotherapy and Proton Beam Radiation Therapy in Treating Patients With Stage II-III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
Official Title
Phase II Trial of Standard Platinum Doublet Chemotherapy + Various Proton Beam Therapy (PBT) Doses in Order to Determine the Optimal Dose of PBT for Unresectable Stage 2/3 Non-Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 31, 2017 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomized phase II trial studies how well platinum doublet chemotherapy and proton beam radiation therapy work in treating patients with stage II-III non-small cell lung cancer that cannot be removed by surgery (unresectable). Drugs used in chemotherapy, such as carboplatin, paclitaxel, etoposide, cisplatin, and pemetrexed work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. Giving platinum doublet chemotherapy and proton beam radiation therapy may work better in treating patients with non-small cell lung cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To compare the 1-year progression-free survival rates of 72 gray (Gy) and 60 Gy conventionally fractionated proton beam therapy (PBT) (as part of concurrent combined modality therapy). SECONDARY OBJECTIVES: I. To assess the adverse events, survival, quality of life, and patterns of failure (local regional, distant metastatic) associated with two dose levels of conventionally fractionated PBT (as part of concurrent combined modality therapy). OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo lower dose proton beam radiation therapy daily for a total of 60 Gy for up to 30 weekdays in the absence of disease progression or unacceptable toxicity. ARM C: Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo higher dose proton beam radiation therapy daily for a total of 72 Gy for up to 36 weekdays in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 3 years and then every 6 months for 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Lung Non-Small Cell Carcinoma, Stage II Lung Non-Small Cell Cancer AJCC v7, Stage IIA Lung Non-Small Cell Carcinoma AJCC v7, Stage IIB Lung Non-Small Cell Carcinoma AJCC v7, Stage III Lung Non-Small Cell Cancer AJCC v7, Stage IIIA Lung Non-Small Cell Cancer AJCC v7, Stage IIIB Lung Non-Small Cell Cancer AJCC v7, Unresectable Lung Non-Small Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A (platinum doublet chemotherapy, lower dose PBT)
Arm Type
Experimental
Arm Description
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo lower dose proton beam radiation therapy daily for a total of 60 Gy for up to 30 weekdays in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm C (platinum doublet chemotherapy, higher dose PBT)
Arm Type
Experimental
Arm Description
Patients receive platinum based doublet chemotherapy consisting of low dose carboplatin and paclitaxel, standard etoposide cisplatin or carboplatin or standard pemetrexed with cisplatin or carboplatin weekly for up to 6 weeks at the discretion of the treating medical oncologist. Patients also undergo higher dose proton beam radiation therapy daily for a total of 72 Gy for up to 36 weekdays in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo
Intervention Description
Chemotherapy
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin
Intervention Description
Chemotherapy
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16
Intervention Description
Chemotherapy
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Intervention Description
Chemotherapy
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Other Intervention Name(s)
MTA, Multitargeted Antifolate, Pemfexy
Intervention Description
Chemotherapy
Intervention Type
Radiation
Intervention Name(s)
Proton Beam Radiation Therapy
Other Intervention Name(s)
PBRT, Proton, Proton EBRT, Proton External Beam Radiotherapy, Proton Radiation Therapy, Radiation, Proton Beam
Intervention Description
Undergo PBT
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Progression free survival (PFS)
Description
A Cox proportional hazards model stratified by stratification factors will be used to model PFS as a function of dose to test for an overall dose effect (a one-sided p-value < 0.10 will be considered as significant evidence of a dose effect). Subsequently, separate Cox models stratified by stratification factors will compare PFS between 72 Gy and 60 Gy (for each, a one-sided p-value < 0.10 will be considered as significant evidence of superiority). Kaplan Meier estimates and curves by dose level will also be generated
Time Frame
From randomization to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
Will be modeled using Cox models. Kaplan-Meier estimates and curves by dose level will also be generated. OS will again be analyzed as exploratory analysis after 50 deaths per primary pairwise comparison have occurred or after all patients have completed follow-up (whichever occurs first).
Time Frame
From randomization to death due to any cause, assessed up to 5 years
Title
Incidence of adverse events
Description
Graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns by dose level (60, 72 Gy). Additionally, the relationship of the adverse event(s) to dose level will be taken into consideration.
Time Frame
Up to 5 years
Title
Local-regional failure
Description
Defined as the time from randomization to the earliest date of documentation of local recurrence. The cumulative incidence of local failure will be estimated using Gray's methodology and compared across dose levels using Fine-Gray quadratic regression (with death as a competing risk).
Time Frame
Up to 5 years
Title
Distant metastasis
Description
Defined as the time from randomization to the earliest date of documentation of distant metastasis. The cumulative incidence of distant metastasis will be estimated using Gray's methodology and compared across dose levels using Fine-Gray quadratic regression (with death as a competing risk).
Time Frame
Up to 5 years
Other Pre-specified Outcome Measures:
Title
Quality of life post treatment
Description
Measured using the single item Linear Analogue Self-Assessment scale. Descriptive statistics by dose level at each time point will include means, standard deviations, medians, and ranges for each scale. Descriptive graphical techniques will include mean plots by dose over time for each scale. Mixed models will be used to compare each scale across dose levels at each post-baseline time point while adjusting for the baseline value of scale. Will graphically explore patterns of missing data and will employ pattern mixture models for longitudinal analyses. The lowest number measuring worst and higher number measuring best outcome.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age >= 18 years Histological confirmation of non-small cell lung cancer Forced expiratory volume in 1 second (FEV1) > 1.0 L Unresectable or medically inoperable stage 2-3 non-small cell lung cancer (based on computed tomography/positron emission tomography [CT/PET], magnetic resonance imaging [MRI] or CT of brain, and physical exam); Eligible if recurrence after surgery and now has the equivalent stage 2-3 non-small cell lung cancer (NSCLC) OR had sub totally resected stage 2-3 NSCLC Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only White blood cell (WBC) >= 3.0 x 10^9/L Absolute neutrophil count (ANC) >= 1.5 x 10^9/L Hemoglobin (Hgb) >= 9 g/dl Platelets (plts) > 100 x 10^9/L Serum creatinine < 1.5 x upper limits of normal (ULN) Serum bilirubin < 1.5 x ULN Provide informed written consent Willing to return to enrolling institution for follow-up for a minimum of 1 year Ability to undergo potentially curative chemotherapy plus radiotherapy Exclusion Criteria: Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Weight loss of > 10% in the past 3 months Distant metastases (M1 disease) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, lupus, usual interstitial pneumonitis (UIP), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Receiving any investigational agent, that would be considered as a treatment for the primary neoplasm Active second malignancy History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias Received chemotherapy for lung cancer within 6 months of registration Previous chest radiotherapy that would overlap with the proton field
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven E Schild
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

Platinum Doublet Chemotherapy and Proton Beam Radiation Therapy in Treating Patients With Stage II-III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

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