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Hypofractionated Boost Before Chemoradiation for Patients With Stage II-III Non-small Cell Lung Cancer Unsuitable for Surgery

Primary Purpose

Recurrent Non-small Cell Lung Cancer, Stage IIA Non-small Cell Lung Cancer, Stage IIB Non-small Cell Lung Cancer

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
hypofractionated radiation therapy
cisplatin
etoposide
3-dimensional conformal radiation therapy
laboratory biomarker analysis
Sponsored by
Ohio State University Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Non-small Cell Lung Cancer focused on measuring Non-small cell, Lung Cancer, Chemoradiation

Eligibility Criteria

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

Inclusion Criteria:

  • All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0) =< grade 1 (except alopecia) at the time of enrollment
  • Adequate baseline organ function obtained within 30 days of study registration
  • Absolute neutrophil count >= 1.5 x 10^9/L
  • Hemoglobin >= 9 g/dL
  • Platelets >= 100 x 10^9/L
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
  • Creatinine =< 1.5 ULN AND
  • Calculated creatinine >= 50 mL/min (calculated by the Cockcroft-Gault formula) or
  • 24-hour urine creatinine clearance >= 50 mL/min
  • Non-small cell lung cancer (NSCLC), histologically and/or cytologically proven
  • Clinical American Joint Committee on Cancer (AJCC) stage (7th edition) IIA-IIIB NSCLC (T1-4N1-3M0)
  • Patients must be considered unresectable or medically-inoperable
  • Patients must have primary tumor =< 6 cm as defined by CT largest axial dimension
  • Within 60 days of registration: patients must have fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)-CT scan (or CT chest/abdomen/pelvis with IV contrast), and magnetic resonance imaging (MRI) brain with IV contrast (or CT scan of the brain with contrast); a non-contrast MRI scans of the chest/abdomen/pelvis or brain are permitted for workup if patient has allergy to CT contrast or renal insufficiency
  • Within 30 days of registration: patients must have vital signs, history/physical examination, laboratory studies (complete blood count panel [CBCP] with differential, chemistries including liver function tests, creatinine clearance [CrCl] assessment, pregnancy test if needed within 14 days of registration)
  • If a pleural effusion is present and visible on both CT scan AND chest x-ray, the investigator should exclude malignant disease by pleurocentesis to confirm cytologically-negative pleural fluid; if fluid is exudative or cytologically positive for tumor cells, patient is excluded
  • Patients with effusions that are minimal (i.e. not visible on chest x-ray) and that are too small to safely tap are eligible.
  • Life expectancy of at least 12 weeks in the opinion of investigator
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 30 days of registration
  • Patients must have measurable primary tumor (undetectable NSCLC primary tumor is ineligible)
  • Patients must be a minimum of 3 weeks from thoracotomy (if performed) and well-healed before starting treatment
  • Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
  • Women of child-bearing potential (WOCBP) must have a negative pregnancy test within 14 days of registration; urine human gonadotropin (HCG) is an acceptable pregnancy assessment
  • Nursing women may participate only if nursing is discontinued
  • Women/men of reproductive potential must be counseled on contraception/abstinence while receiving the study treatment

Exclusion Criteria:

  • Patients with contralateral hilar involvement (greater than 1.5 cm on short axis or positive on PET scan, or biopsy-proven)
  • Documented or pathologically-proven metastatic disease
  • Presence of nodules considered neoplastic in the same lobe or other ipsilateral lobe as the primary tumor (stage T3-4), unless the nodule can be encompassed in the stereotactic boost (gross tumor volume [GTV]boost) without exceeding a total GTVboost size of 6 cm as defined by CT largest axial dimension
  • Presence of nodules considered neoplastic in contralateral lobes (M1a)
  • Patients with history of pneumonectomy
  • Prior cytotoxic chemotherapy or molecularly-targeted agents (e.g. erlotinib, crizotinib), unless > 2 years prior
  • Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, or carcinoma in situ of the cervix; patients with a previous malignancy without evidence of disease for >= 3 years will be allowed to enter the trial
  • History of active connective tissue disease (scleroderma) or idiopathic pulmonary fibrosis
  • History of previous radiation therapy which would result in overlapping radiation fields
  • Uncontrolled neuropathy grade 2 or greater, regardless of cause
  • Subjects who are breast-feeding and plan to continue breast-feeding during therapy, or have a positive pregnancy test will be excluded from the study; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Medical contraindication to MR imaging (e.g. pacemakers, metallic implants, aneurysm clips, known contrast allergy to Gadolinium contrast, pregnancy, nursing mothers, weight greater than 350 pounds) [first 10 patients]
  • Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator; this could include severe, active co-morbidities such as:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last months
    • Transmural myocardial infarction within the last 6 months
    • Acquired immune deficiency syndrome (AIDS) based upon the current CDC definition; note, however, that HIV testing is not required for entry to protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved may be significantly immunosuppressive
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration
    • Hepatic insufficiency resulting in jaundice and/or coagulation defects

Sites / Locations

  • Ohio State University Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (hypofractionated radiation boost, chemoradiation)

Arm Description

Patients undergo hypofractionated radiation boost over 2 fractions (at least 40 hours apart) during week 1. Beginning week 2, patients receive cisplatin IV on days 8, 15, 36, and 43; and etoposide IV over 60 minutes on days 8-12 and 36-40. Patients also undergo standard 3-D conformal radiation therapy QD 5 days a week for a total of 30 fractions. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Primary tumor control rate, as measured from the time of treatment completion until the first documented date of local failure
Primary tumor control rate at 12 months, as well its 95% confidence interval, will be reported for all eligible subjects received treatment.

Secondary Outcome Measures

Frequency of all adverse events, with special attention to grade 3-5 esophagitis, pneumonitis, and cardiac adverse events as defined by the National Cancer Institution Common Terminology Criteria for Adverse Events CTCAE version 4.0
Tolerability measured by the number of patients who discontinue treatment
Regional control
Distant control
Progression-free survival (PFS)
Kaplan-Meier (K-M) analysis will be used to estimate PFS.
Overall survival (OS)
K-M analysis will be used to estimate OS.
Objective response rate as measured by Response Evaluation Criteria in Solid Tumors criteria
Changes in tumor perfusion measured by MR-DCE/PWI
Changes in perfusion will be tested by comparing mean values pre- and post-hypofractionated boost radiation using a paired t-test.
Changes in diffusion measured by MR-diffusion
Changes in diffusion will be tested by comparing mean values pre- and post-hypofractionated boost radiation using a paired t-test.
Changes in hypoxia measured by BOLD sequences
Changes in hypoxia will be tested by comparing mean values pre- and post-hypofractionated boost radiation using a paired t-test.

Full Information

First Posted
October 7, 2014
Last Updated
March 21, 2023
Sponsor
Ohio State University Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT02262325
Brief Title
Hypofractionated Boost Before Chemoradiation for Patients With Stage II-III Non-small Cell Lung Cancer Unsuitable for Surgery
Official Title
A Phase II Trial Combining Hypofractionated Radiation Boost With Conventionally-Fractionated Chemoradiation in Locally Advanced Non-small Cell Lung Cancer Not Suitable for Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 8, 2015 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University Comprehensive Cancer Center

4. Oversight

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

5. Study Description

Brief Summary
This phase II trial studies how well giving a hypofractionated boost to the primary tumor before standard chemotherapy and radiation therapy works in treating patients with stage II or III non-small cell lung cancer that cannot be removed by surgery. Advances in radiation oncology have allowed better radiation targeting which may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin and etoposide, 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 x-rays to kill tumor cells. Giving more precise and targeted radiation before standard chemotherapy and radiation therapy may kill more tumor cells and prevent the cancer from coming back in the location in which it started.
Detailed Description
PRIMARY OBJECTIVES: I. To estimate the primary tumor control rate at 12 months. SECONDARY OBJECTIVES: I. To further establish safety and tolerability of this regimen. II. To estimate the rates of regional, distant control as well as progression-free survival and overall survival. III. To evaluate the objective response rate (ORR) to this regimen. IV. To evaluate the response of tumors to stereotactic (high-dose) radiation using magnetic resonance tumor perfusion imaging modalities (magnetic resonance [MR]-dynamic contrast-enhanced [DCE]/perfusion weighted imaging [PWI], MR-diffusion, blood oxygenation level dependent [BOLD] sequences). OUTLINE: Patients will receive a hypofractionated boost to the primary tumor over 2 fractions (at least 40 hours apart) during week 1. Beginning week 2, patients receive cisplatin intravenously (IV) on days 8, 15, 36, and 43; and etoposide IV over 60 minutes on days 8-12 and 36-40. If carboplatin and paclitaxel is administered concurrently with radiotherapy, 2 cycles of carboplatin (AUC=6 mg/min/mL IV on day 1, 22) and paclitaxel (200 mg/m2 IV on day 1, 22) consolidation chemotherapy are required, to be administered starting 4-6 weeks after concurrent chemoradiation has ended. Each cycle is 21 days long. If cisplatin and etoposide is administered concurrently with radiotherapy, consolidation chemotherapy is not allowed. Patients also undergo standard conformal radiation therapy once daily (QD) 5 days a week for a total of 30 fractions. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Non-small Cell Lung Cancer, Stage IIA Non-small Cell Lung Cancer, Stage IIB Non-small Cell Lung Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer
Keywords
Non-small cell, Lung Cancer, Chemoradiation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (hypofractionated radiation boost, chemoradiation)
Arm Type
Experimental
Arm Description
Patients undergo hypofractionated radiation boost over 2 fractions (at least 40 hours apart) during week 1. Beginning week 2, patients receive cisplatin IV on days 8, 15, 36, and 43; and etoposide IV over 60 minutes on days 8-12 and 36-40. Patients also undergo standard 3-D conformal radiation therapy QD 5 days a week for a total of 30 fractions. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention Type
Radiation
Intervention Name(s)
hypofractionated radiation therapy
Other Intervention Name(s)
SBRT
Intervention Description
Radiation boost in week 1 (days 1-5)
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
CACP, CDDP, CPDD, DDP
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
EPEG, VP-16, VP-16-213
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
3-dimensional conformal radiation therapy
Other Intervention Name(s)
3D conformal radiation therapy, 3D-CRT
Intervention Description
Undergo 3-dimensional conformal radiation therapy
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Primary tumor control rate, as measured from the time of treatment completion until the first documented date of local failure
Description
Primary tumor control rate at 12 months, as well its 95% confidence interval, will be reported for all eligible subjects received treatment.
Time Frame
At 12 months following chemo/RT
Secondary Outcome Measure Information:
Title
Frequency of all adverse events, with special attention to grade 3-5 esophagitis, pneumonitis, and cardiac adverse events as defined by the National Cancer Institution Common Terminology Criteria for Adverse Events CTCAE version 4.0
Time Frame
Up to 30 days after completion of treatment
Title
Tolerability measured by the number of patients who discontinue treatment
Time Frame
Up to 5 years
Title
Regional control
Time Frame
Up to 24 months
Title
Distant control
Time Frame
Up to 24 months
Title
Progression-free survival (PFS)
Description
Kaplan-Meier (K-M) analysis will be used to estimate PFS.
Time Frame
From date of treatment initiation to progression, assessed up to 24 months
Title
Overall survival (OS)
Description
K-M analysis will be used to estimate OS.
Time Frame
Up to 24 months
Title
Objective response rate as measured by Response Evaluation Criteria in Solid Tumors criteria
Time Frame
Up to 5 years
Title
Changes in tumor perfusion measured by MR-DCE/PWI
Description
Changes in perfusion will be tested by comparing mean values pre- and post-hypofractionated boost radiation using a paired t-test.
Time Frame
Baseline to the end of week 1
Title
Changes in diffusion measured by MR-diffusion
Description
Changes in diffusion will be tested by comparing mean values pre- and post-hypofractionated boost radiation using a paired t-test.
Time Frame
Baseline to the end of week 1
Title
Changes in hypoxia measured by BOLD sequences
Description
Changes in hypoxia will be tested by comparing mean values pre- and post-hypofractionated boost radiation using a paired t-test.
Time Frame
Baseline to the end of week 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0) =< grade 1 (except alopecia) at the time of enrollment Adequate baseline organ function obtained within 30 days of study registration Absolute neutrophil count >= 1.5 x 10^9/L Hemoglobin >= 9 g/dL Platelets >= 100 x 10^9/L Total bilirubin =< 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN Creatinine =< 1.5 ULN AND Calculated creatinine >= 50 mL/min (calculated by the Cockcroft-Gault formula) or 24-hour urine creatinine clearance >= 50 mL/min Non-small cell lung cancer (NSCLC), histologically and/or cytologically proven Clinical American Joint Committee on Cancer (AJCC) stage (7th edition) IIA-IIIB NSCLC (T1-4N1-3M0) Patients must be considered unresectable or medically-inoperable Patients must have primary tumor =< 6 cm as defined by CT largest axial dimension Within 60 days of registration: patients must have fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)-CT scan (or CT chest/abdomen/pelvis with IV contrast), and magnetic resonance imaging (MRI) brain with IV contrast (or CT scan of the brain with contrast); a non-contrast MRI scans of the chest/abdomen/pelvis or brain are permitted for workup if patient has allergy to CT contrast or renal insufficiency Within 30 days of registration: patients must have vital signs, history/physical examination, laboratory studies (complete blood count panel [CBCP] with differential, chemistries including liver function tests, creatinine clearance [CrCl] assessment, pregnancy test if needed within 14 days of registration) If a pleural effusion is present and visible on both CT scan AND chest x-ray, the investigator should exclude malignant disease by pleurocentesis to confirm cytologically-negative pleural fluid; if fluid is exudative or cytologically positive for tumor cells, patient is excluded Patients with effusions that are minimal (i.e. not visible on chest x-ray) and that are too small to safely tap are eligible. Life expectancy of at least 12 weeks in the opinion of investigator Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 30 days of registration Patients must have measurable primary tumor (undetectable NSCLC primary tumor is ineligible) Patients must be a minimum of 3 weeks from thoracotomy (if performed) and well-healed before starting treatment Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed Women of child-bearing potential (WOCBP) must have a negative pregnancy test within 14 days of registration; urine human gonadotropin (HCG) is an acceptable pregnancy assessment Nursing women may participate only if nursing is discontinued Women/men of reproductive potential must be counseled on contraception/abstinence while receiving the study treatment Exclusion Criteria: Patients with contralateral hilar involvement (greater than 1.5 cm on short axis or positive on PET scan, or biopsy-proven) Documented or pathologically-proven metastatic disease Presence of nodules considered neoplastic in the same lobe or other ipsilateral lobe as the primary tumor (stage T3-4), unless the nodule can be encompassed in the stereotactic boost (gross tumor volume [GTV]boost) without exceeding a total GTVboost size of 6 cm as defined by CT largest axial dimension Presence of nodules considered neoplastic in contralateral lobes (M1a) Patients with history of pneumonectomy Prior cytotoxic chemotherapy or molecularly-targeted agents (e.g. erlotinib, crizotinib), unless > 2 years prior Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, or carcinoma in situ of the cervix; patients with a previous malignancy without evidence of disease for >= 3 years will be allowed to enter the trial History of active connective tissue disease (scleroderma) or idiopathic pulmonary fibrosis History of previous radiation therapy which would result in overlapping radiation fields Uncontrolled neuropathy grade 2 or greater, regardless of cause Subjects who are breast-feeding and plan to continue breast-feeding during therapy, or have a positive pregnancy test will be excluded from the study; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Medical contraindication to MR imaging (e.g. pacemakers, metallic implants, aneurysm clips, known contrast allergy to Gadolinium contrast, pregnancy, nursing mothers, weight greater than 350 pounds) [first 10 patients] Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator; this could include severe, active co-morbidities such as: Unstable angina and/or congestive heart failure requiring hospitalization within the last months Transmural myocardial infarction within the last 6 months Acquired immune deficiency syndrome (AIDS) based upon the current CDC definition; note, however, that HIV testing is not required for entry to protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved may be significantly immunosuppressive Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration Hepatic insufficiency resulting in jaundice and/or coagulation defects
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Miller, MD
Organizational Affiliation
Ohio State University Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://cancer.osu.edu
Description
The Jamesline

Learn more about this trial

Hypofractionated Boost Before Chemoradiation for Patients With Stage II-III Non-small Cell Lung Cancer Unsuitable for Surgery

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