Clinical trial NCT01459497: Hypofractionated Image-Guided Radiation Therapy (IGRT) in Patients With Stage II-III Non-Small Cell Lung Cancer
Official title: Phase III Randomized Study of Standard Versus Accelerated Hypofractionated Image-Guided Radiation Therapy (IGRT) in Patients With Stage II-III Non-Small Cell Lung Cancer and Poor Performance Status
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Keywords: non-small cell lung cancer
Stages II or III non-small cell lung cancer
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2011-10-25
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is designed to determine whether an accelerated course of hypofractionated radiation therapy with daily image guidance and motion assessment/control will allow more effective treatment of poor performance status patients with stage II-III NSCLC, who would benefit from local therapy compared to standard radiation therapy (60 Gy in 2 Gy per fraction).

Detailed description: The study is designed to determine whether an accelerated course of hypofractionated radiation therapy with daily image guidance and motion assessment/control will allow more effective treatment of poor performance status patients with stage II-III NSCLC, who would benefit from local therapy compared to standard radiation therapy (60 Gy in 2 Gy per fraction). Poor performance status patients can be a heterogeneous group, with tumor-related factors, other co-morbidities, or advanced age placing patients in the category. These patients have traditionally been underrepresented in clinical trials, and thus no prospective study has evaluated the efficacy of other radiotherapy dose fractionations in these patients. One phase III trial of "poor-risk" locally advanced NSCLC (RTOG 93-04) included just over 40% Karnofsky performance status 60-70 patients and showed median survival times of 9.5 and 10.3 months with 60Gy of conventional radiation therapy alone or with recombinant β-interferon \[18\]. 1 year overall survival was just 44% in these patients.

This study includes randomization to two arms. Arm A (experimental arm) will include IGRT, 60 Gy in 15 fractions (3 weeks). Arm B will include conventional radiation, 60-66 Gy in 30-33 fractions (6 weeks) with optional concurrent with carboplatin/taxol .

The experimental arm dose for this trial is based on a dose escalation trial at University of Texas Southwestern evaluating the maximum tolerated dose of hypofractionated IGRT in this patient population (Phase I study IRB #072010-050). Doses were escalated from 3 Gy per fraction (total dose 45 Gy) to 4 Gy per fraction (total dose 60 Gy) and evaluation for treatment related toxicity was being performed. Critical structure dose constraints will be expressed as organ dose-volume limits, with limits formulated with the approval of the study investigators using known tolerance data, radiobiological conversion models, and norms used in current practice at academic centers \[27\].

Randomization Schema:

Patients will be allocated to the treatment using a randomized permuted block within strata to balance for patient factors other than institution. The stratifying variables are Zubrod performance status (2 vs. \> 2) and stage (II vs. III).

Eligibility criteria: Inclusion Criteria:

* All patients must be willing and capable to provide informed consent to participate in the protocol.
* Patients must have appropriate staging studies identifying them as AJCC stage II or III non small cell lung cancer, (according to AJCC Staging, 6th edition; see appendix III), or recurrent non small cell lung cancer. Histologic confirmation of cancer will be required by biopsy or cytology within 6 months of study entry.
* Patients must have the potential for benefit from local therapy (at the discretion of the investigator).
* The patient's Zubrod performance status must be 2 or greater OR patients with Zubrod performance status 0-1 and weight loss \>10% are considered eligible. In addition, patients determined to be medically unfit or refusing combined modality therapy are eligible.
* Age ≥ 18.
* Patients must have measurable or evaluable disease.
* Women of childbearing potential and male participants must agree to use an effective method of contraception.
* Patients must sign study specific informed consent prior to study entry.
* Patients must not have plans for concurrent chemoradiation therapy.
* Patients must complete all required pretreatment evaluations

Exclusion Criteria:

* Total (aggregate) gross tumor volume \> 500 cm3 (500 cc's or 0.5 Liters)
* Prior radiotherapy to the region of the study cancer that would result in direct overlap of radiation therapy fields.
* Chemotherapy given within one week of study registration.
* Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus.

Primary outcomes:
measure: Overall Survival of Standard Radiation (CFRT) Versus Accelerated, Hypofractionated, Image-guided Conformal Radiotherapy (IGRT) in Treatment of Stage II-III NSCLC in Patients With Poor Performance Status at 1 Year.
timeFrame: 1 year
Secondary outcomes:
measure: Toxicities of Two Radiotherapy Treatment Regimens in Patients With Stage II-III Non-Small Cell Lung Cancer (NSCLC) and Poor Performance Status
timeFrame: 60 months
measure: Time to Local Progression of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status
timeFrame: 60 months
measure: Disease-free Survival of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.
timeFrame: 60 months
measure: Quality of Life of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.
timeFrame: 6 months
measure: Cost Effectiveness of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.
timeFrame: 2 years
measure: Quality Adjusted Life Survival Time of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.
timeFrame: 20 months
measure: Quality Adjusted Life Survival Time of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.
timeFrame: 20 months
Other outcomes:
Locations:
city: Austin
country: United States
facility: Georgetown Cancer Center (Austin Cancer Center)
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: Irving
country: United States
facility: Baylor Research Institute Dallas, Baylor Irving
state: Texas
city: Sherman
country: United States
facility: Texas Oncology - Sherman
state: Texas
city: Temple
country: United States
facility: Scott & White Memorial Temple
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Puneeth Iyengar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: puneeth.iyengar@utsouthwestern.edu
name: Puneeth Iyengar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Iyengar P, Zhang-Velten E, Court L, Westover K, Yan Y, Lin MH, Xiong Z, Patel M, Rivera D, Chang J, Saunders M, Shivnani A, Lee A, Hughes R, Gerber D, Dowell J, Gao A, Heinzerling J, Li Y, Ahn C, Choy H, Timmerman R. Accelerated Hypofractionated Image-Guided vs Conventional Radiotherapy for Patients With Stage II/III Non-Small Cell Lung Cancer and Poor Performance Status: A Randomized Clinical Trial. JAMA Oncol. 2021 Oct 1;7(10):1497-1505. doi: 10.1001/jamaoncol.2021.3186.