Phase I Study of Accelerated Hypofractionated Image-Guided Radiation Therapy

Phase I Study of Accelerated Hypofractionated Image-Guided Radiation Therapy (IGRT) in Patients With Stage II-IV Non-Small Cell Lung Cancer and Poor Performance Status

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03623334

Enrollment

Registered

2018-08-09

Start date

2009-10-05

Completion date

2018-02-10

Last updated

2021-05-04

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

Conditions

Non-small Cell Lung Cancer

Brief summary

The study is designed to determine whether daily image guidance and motion assessment/control will allow treatment of poor performance status patients with stage II-IV NSCLC, who would benefit from local therapy, with an accelerated course of hypofractionated radiation therapy.

Detailed description

Subjects for this study will be enrolled by the Moncrief Radiation oncology Department at the Simmons Cancer Center. Primary objective: To escalate the dose of accelerated, hypofractionated, image-guided conformal radiotherapy to a potent tumorcidal dose without exceeding the maximum tolerated dose in treatment of stage ii-iV nSCLC in patients with poor performance status. Secondary objectives: To evaluate local regional tumor control and overall survival in patients with stage ii-iV nSCLC and poor performance status treated with accelerated, hypofractionated, image-guided conformal radiotherapy. Schema number of patients between 7-45 (depending on tolerance) Patients in each dose cohort will all be treated as a single group for dose escalation. The starting dose will be 3.33 Gy per fraction for 15 fractions (total dose 50 Gy). Subsequent cohorts of patients will receive a higher dose per fraction as follows: Cohort No. Fractions Dose per fraction (Gy) Total Dose (Gy) No. Patients 1. 15 3.33 50 7-15 2. 15 3.67 55 7-15 3. 15 4.00 60 7-15 Minimum waiting periods will be assigned between each dose cohort to observe toxicity. Screening Procedures each study participant will have the following exams, tests or procedure to help determine if they are qualified to be in this study: Within 8 weeks of enrollment : * Computed tomographic (CT) with contrast of the lung and upper abdomen. a CT done in conjunction with a Positron emission Tomography (PeT) scan is satisfactory as long as the images are of adequate quality to be interpreted by a radiologist. * an MRi of the brain with contrast (or CT if MRi is medically contraindicated). * Complete Blood Count (CBC) with differential * Charleston Comorbidity index completion Within 3 days prior to radiotherapy: urine or serum pregnancy test in females of child-bearing capacity. Within 12 weeks of enrollment: \* Pulmonary function tests including spirometry for forced expiratory volume in 1 second (FeV-1), diffusing capacity (DLCo), and arterial blood gas (Pao-2). Prior to enrollment on the study: Tissue biopsy or cytology confirming non-small cell lung cancer. Treatment Protocol treatment must begin within 4 weeks after patient registration to the trial. Patients will receive 15 fractions of radiation. Total dose will depend on the dose cohort of the study (see schema). The starting dose level will be 3.33 Gy per fraction for 15 fractions (total dose \[?\] 50 Gy). Patients must not receive other concomitant antineoplastic therapy (including standard fractionated radiotherapy to the chest, chemotherapy, biological therapy, vaccine therapy, and surgery) within a week prior to, during, or within one week after completing hypofractionated image-guided radiation therapy on protocol. Follow-up Patients will be followed until death.

Interventions

RADIATIONImage-Guided Radiation Therapy

Radiotherapy to a potent tumorcidal dose

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 99 Years

Healthy volunteers

Inclusion criteria

1. All patients must be willing and capable to provide informed consent to participate in the protocol. 2. Patients must have appropriate staging studies identifying them as AJCC stage II, III or IV 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. 3. Patients must have the potential for benefit from local therapy (at the discretion of the investigator). 4. Patient must have a Zubrod performance status of 2 or greater Or Patient must have had \>10% weight loss in the past 6 months Or Patient is not eligible for concurrent chemoradiation as determined by a Medical Oncologist and Radiation Oncologist 5. Age ≥ 18. 6. The tumor must be ineligible for definitive surgical resection. 7. The tumor must be ineligible for stereotactic body radiation therapy. 8. Patients must have measurable or evaluable disease. 9. Women of childbearing potential and male participants must agree to use an effective method of contraception. 10. Patients must sign study specific informed consent prior to study entry. 11. Patients must complete all required pretreatment evaluations

Exclusion criteria

1. Evidence of small cell histology. 2. Tumor eligible for definitive surgical resection. 3. Tumor eligible for definitive stereotactic body radiation therapy. 4. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields. 5. Chemotherapy given within one week of study registration. 6. Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Dose Limiting Toxicity	90 days after start of treatment up to 1 year	A dose limiting toxicity (DLT) is defined as treatment-related (definitely and probably, but not possibly related to treatment\*) grade 3 adverse events (per CTCAE, v.3.0, with the exception of pulmonary function tests)

Secondary

Measure	Time frame	Description
Number of Participants With Local Regional Tumor Control at 6 Months	6 months	Local control is defined as the absence of isolated progression (stable disease or responsive disease at last follow-up) within the primary tumor. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions.
Number of Participants With Local Regional Tumor Control at 9 Months	9 months	Local control is defined as the absence of isolated progression (stable disease or responsive disease at last follow-up) within the primary tumor. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions.
Number of Participants With Local Regional Tumor Control at 12 Months	12 months	Local control is defined as the absence of isolated progression (stable disease or responsive disease at last follow-up) within the primary tumor. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions.
Number of Participants With Local Regional Tumor Control at 3 Months	3 months	Local control is defined as the absence of isolated progression (stable disease or responsive disease at last follow-up) within the primary tumor. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions.
Number of Participants With Local Regional Tumor Control at 20 Months	20 months	Local control is defined as the absence of isolated progression (stable disease or responsive disease at last follow-up) within the primary tumor. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions.
Overall Survival at 6 Months	6 months	Overall survival is defined as participants alive during the research period.
Number of Participants With Local Regional Tumor Control at 16 Months	16 months	Local control is defined as the absence of isolated progression (stable disease or responsive disease at last follow-up) within the primary tumor. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions.

Participant flow

Participants by arm

Arm	Count
Dose Level A: IGRT 3.33Gy x 15 Fractions (Total 50Gy) Image-guided radiation therapy (IGRT) does of 3.33Gy for 15 fractions (total dose = 50 Gy) which is given over the course of about 3 weeks	15
Dose Level B: IGRT 3.67Gy x 15 Fractions (Total 55Gy) Image-guided radiation therapy (IGRT) dose of 3.67Gy for 15 fractions (total dose = 55 Gy) which is given over the course of about 3 weeks	21
Dose Level C: IGRT 4Gy x 15 Fractions ( Total 60Gy) 4 Gy per fraction for a total dose of 60 Gy will be tested. Image-guided radiation therapy (IGRT) dose which is given over the course of about 3 weeks Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy.	19
Total	55

Baseline characteristics

Characteristic	Dose Level A: IGRT 3.33Gy x 15 Fractions (Total 50Gy)	Dose Level B: IGRT 3.67Gy x 15 Fractions (Total 55Gy)	Dose Level C: IGRT 4Gy x 15 Fractions ( Total 60Gy)	Total
Age, Continuous	65 years	65 years	65 years	65 years
Sex: Female, Male Female	3 Participants	10 Participants	11 Participants	24 Participants
Sex: Female, Male Male	12 Participants	11 Participants	8 Participants	31 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	14 / 15	14 / 21	11 / 19
other Total, other adverse events	15 / 15	20 / 21	18 / 19
serious Total, serious adverse events	5 / 15	4 / 21	4 / 19

Outcome results

Primary

Number of Participants With Dose Limiting Toxicity

A dose limiting toxicity (DLT) is defined as treatment-related (definitely and probably, but not possibly related to treatment\*) grade 3 adverse events (per CTCAE, v.3.0, with the exception of pulmonary function tests)

Time frame: 90 days after start of treatment up to 1 year

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Dose Level A: IGRT 3.33Gy x 15 Fractions (50 Gy)	Number of Participants With Dose Limiting Toxicity	1 Participants
Dose Level B: IGRT 3.67Gy x 15 Fractions (55 Gy)	Number of Participants With Dose Limiting Toxicity	1 Participants
Dose Level C: IGRT 4.00Gy x 15 Fractions (60 Gy)	Number of Participants With Dose Limiting Toxicity	1 Participants

Secondary

Number of Participants With Local Regional Tumor Control at 12 Months

Local control is defined as the absence of isolated progression (stable disease or responsive disease at last follow-up) within the primary tumor. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions.

Time frame: 12 months