A Phase II Trial Combining Hypofractionated Radiation Boost With Conventionally-Fractionated Chemoradiation in Locally Advanced Non-small Cell Lung Cancer Not Suitable for Surgery
Overview
- Phase
- Phase 2
- Intervention
- hypofractionated radiation therapy
- Conditions
- Recurrent Non-small Cell Lung Cancer
- Sponsor
- Ohio State University Comprehensive Cancer Center
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Primary Tumor Control Rate, as Measured From the Time of Treatment Completion Until the First Documented Date of Local Failure
- Status
- Completed
- Last Updated
- 10 months ago
Overview
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.
Investigators
Eric Miller
Principal Investigator
Ohio State University Comprehensive Cancer Center
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
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
Arms & Interventions
Treatment (hypofractionated radiation boost, chemoradiation)
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: hypofractionated radiation therapy
Treatment (hypofractionated radiation boost, chemoradiation)
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: cisplatin
Treatment (hypofractionated radiation boost, chemoradiation)
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: etoposide
Treatment (hypofractionated radiation boost, chemoradiation)
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: 3-dimensional conformal radiation therapy
Treatment (hypofractionated radiation boost, chemoradiation)
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: laboratory biomarker analysis
Outcomes
Primary Outcomes
Primary Tumor Control Rate, as Measured From the Time of Treatment Completion Until the First Documented Date of Local Failure
Time Frame: At 12 months following chemo/radiation therapy
Primary tumor control rate at 12 months, as well its 95% confidence interval, will be reported for all eligible subjects received treatment.
Secondary Outcomes
- Number of Adverse Events(Up to 30 days after completion of treatment, up to 5 years)
- Tolerability Measured by the Number of Patients Who Discontinue Treatment(Up to 5 years)
- Regional Control(Up to 24 months)
- Distant Control(Up to 24 months)
- Disease-free Survival (DFS)(From date of treatment initiation to progression, assessed up to 24 months)
- Overall Survival (OS)(Up to 24 months)
- Objective Response Rate as Measured by Response Evaluation Criteria in Solid Tumors Criteria(At 3 months and 6 months)
- Changes in Tumor Perfusion Measured by MR-DCE/PWI Amp and Kep(Baseline to the end of week 1)
- Changes in Tumor Perfusion Measured by MR-DCE/PWI Kpe and Kel(Baseline to the end of week 1)
- Changes in Diffusion Measured by MR-diffusion(Baseline to the end of week 1)
- Changes in Hypoxia Measured by BOLD Sequences(Baseline to the end of week 1)