Phase I Trial Of IMRT Using A Contralateral Esophagus Sparing Technique (CEST) In Locally Advanced Lung Cancer

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02394548
• Collaborator: (none)
• Enrollment: 27
• Locations: 2
• Arm: 1
• Duration (Months): 69
• Patients Per Site: 13.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This research study is examining the benefit of a novel radiation planning approach on the likelihood of developing severe esophagitis (irritation and inflammation of the esophagus) during the course of radiation therapy with concurrent chemotherapy which is associated with very painful and difficult swallowing.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Carcinoma; Small Cell Lung Carcinoma	Radiation: Contralateral Esophageal Sparing Technique (CEST)	N/A

Detailed Description

This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.

The U.S. Food and Drug Administration (FDA) has approved radiation with chemotherapy as a treatment option for your disease.

Currently, there are no established rules to avoid esophagitis in the treatment of lung cancer with radiation therapy. We have developed an IMRT-based technique, termed CEST, to reduce the radiation dose to the part of the esophagus that is located opposite to the tumor. The reason behind this approach is that a lower radiation dose causes less esophagus inflammation and irritation and, therefore, may preserve the swallowing function of the esophagus better. In our clinical experience, reducing the radiation dose to part of the esophagus in this fashion has shown the potential to dramatically decrease the likelihood of severe esophagitis in many though not all people with lung cancer. We therefore wish to analyze this technique further.

There is no firm data to indicate that different chemotherapy regimens given at the same time of radiation therapy result in different rates of esophagitis. The Investigators will, therefore, allow any type of standard-of-care chemotherapy regimen at the discretion of the patient's medical oncologist.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Trial Of Intensity-Modulated Radiation Therapy (IMRT) Using A Contralateral Esophagus Sparing Technique (CEST) In Locally Advanced Non-Small Cell Lung Cancer (NSCLC) And Limited-Stage Small Cell Lung Cancer (LS-SCLC).
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Feb 1, 2019
• Actual Study Completion Date: Mar 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Contralateral Esophagus Sparing Technique (CEST) IMRT with CEST and concurrent chemotherapy (any standard-of-care regimen)	Radiation: Contralateral Esophageal Sparing Technique (CEST); Determine whether CEST decreases rate of severe acute esophagitis

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Grade 3 or Higher Acute Esophagitis (CTCAE) [up to 3 months]

   Esophagitis will be measured using the Common Toxicity Criteria for Adverse Effects (CTCAE) v4 scoring scale

Secondary Outcome Measures

1. Number of Participants With Grade 3 or Higher Acute Esophagitis (RTOG) [Baseline , up to 3 Months]

   Esophagitis will be measured using the historical Radiation Therapy Oncology Group (RTOG) scoring scale

2. Number of Participants With Adverse Events [Baseline, up to 2 Years]

   Adverse events will be measured using CTCAE v4 scoring scale

3. Rate of Local and Regional Failure [Median follow-up of up to 2 years]

   Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline. No isolated locoregional tumor failures at a median follow-up of up to 2 years.

4. Overall Survival Rate [2 Years]

   Follow-up time will be calculated from the date of registration to the date of death or the last follow-up date on which the patient was reported alive. Overall survival rates will be estimated using the Kaplan-Meier method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Participants must meet the following criteria on screening examination to be eligible to participate in the study.

• Histologically or cytologically proven diagnosis of NSCLC or SCLC

• NSCLC, patients with clinical stage IIB-IV patients (AJCC, 7th ed.) are eligible, and for SCLC, limited-stage patients are eligible, if documented to be a candidate for definitive radiation and concurrent chemotherapy in the radiation oncologist or medical oncologist clinic note.

• Stage IV NSCLC patients are eligible only if they have a solitary brain metastasis

• Patients with non-malignant pleural effusion are eligible. --- If a pleural effusion is present, the following criteria must be met to exclude malignant involvement:

• When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative.

• Exudative pleural effusions are excluded, regardless of cytology;

• Effusions that are minimal (ie, not visible on chest x-ray) that are too small to safely tap are eligible.

• Gross tumor (primary tumor or involved lymph node) must be within 1 cm of esophagus on the most recent chest CT scan.

• ECOG performance status 0-1 within 30 days prior to registration;

• Age ≥18

• Women of childbearing potential must indicate that there is not a possibility of being pregnant at the time of enrollment or have a negative serum pregnancy test prior to the initiation of radiation therapy.

• Women of childbearing potential and male participants must practice adequate contraception.

• Patient must provide study-specific informed consent prior to study entry.

Exclusion Criteria:

Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.

• Greater than minimal, exudative, or cytologically positive pleural effusions

• Tumor suspected or known to invade the esophagus

• Prior chemotherapy if this precludes administration of concurrent chemotherapy for protocol treatment. Note that induction chemotherapy is allowed as long as concurrent chemotherapy is possible.

• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

• Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.

• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

• Any history of allergic reaction to chemotherapies used

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02115
2	Newton-Wellesley Hospital	Newton	Massachusetts	United States	02462

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: Henning Willers, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 22, 2017
• Informed Consent Form - Nov 1, 2018

More Information

Publications

None provided.

• Responsible Party: Henning Willers, M.D., Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02394548
• Other Study ID Numbers: 15-023
• First Posted: Mar 20, 2015
• Last Update Posted: Dec 9, 2021
• Last Verified: Dec 1, 2021

• Keywords provided by Henning Willers, M.D., Principal Investigator, Massachusetts General Hospital: Locally advanced, inoperable non-small cell lung carcinoma; Limited stage small cell lung carcinoma; Acute esophagitis; Intensity-modulated radiation therapy
• Additional relevant MeSH terms: Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma

Study Results

Participant Flow

Pre-assignment Detail	One participant was consented but never began treatment

Arm/Group Title	Contralateral Esophagus Sparing Technique (CEST)
Arm/Group Description	IMRT with CEST and concurrent chemotherapy (any standard-of-care regimen) Contralateral Esophageal Sparing Technique (CEST): Determine whether CEST decreases rate of severe acute esophagitis
Period Title: Overall Study
STARTED	26
COMPLETED	25
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Contralateral Esophagus Sparing Technique (CEST)
Arm/Group Description	IMRT with CEST and concurrent chemotherapy (any standard-of-care regimen) Contralateral Esophageal Sparing Technique (CEST): Determine whether CEST decreases rate of severe acute esophagitis
Overall Participants	26
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67
Sex: Female, Male (Count of Participants)
Female	11 42.3%
Male	15 57.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.8%
Not Hispanic or Latino	22 84.6%
Unknown or Not Reported	3 11.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	23 88.5%
More than one race	0 0%
Unknown or Not Reported	3 11.5%
Region of Enrollment (Count of Participants)
United States	26 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Grade 3 or Higher Acute Esophagitis (CTCAE)
Description	Esophagitis will be measured using the Common Toxicity Criteria for Adverse Effects (CTCAE) v4 scoring scale
Time Frame	up to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Contralateral Esophagus Sparing Technique (CEST)
Arm/Group Description	IMRT with CEST and concurrent chemotherapy (any standard-of-care regimen) Contralateral Esophageal Sparing Technique (CEST): Determine whether CEST decreases rate of severe acute esophagitis
Measure Participants	26
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	Number of Participants With Grade 3 or Higher Acute Esophagitis (RTOG)
Description	Esophagitis will be measured using the historical Radiation Therapy Oncology Group (RTOG) scoring scale
Time Frame	Baseline , up to 3 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Contralateral Esophagus Sparing Technique (CEST)
Arm/Group Description	IMRT with CEST and concurrent chemotherapy (any standard-of-care regimen) Contralateral Esophageal Sparing Technique (CEST): Determine whether CEST decreases rate of severe acute esophagitis
Measure Participants	26
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Adverse events will be measured using CTCAE v4 scoring scale
Time Frame	Baseline, up to 2 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Contralateral Esophagus Sparing Technique (CEST)
Arm/Group Description	IMRT with CEST and concurrent chemotherapy (any standard-of-care regimen) Contralateral Esophageal Sparing Technique (CEST): Determine whether CEST decreases rate of severe acute esophagitis
Measure Participants	26
Count of Participants [Participants]	24 92.3%

4. Secondary Outcome

Title	Rate of Local and Regional Failure
Description	Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline. No isolated locoregional tumor failures at a median follow-up of up to 2 years.
Time Frame	Median follow-up of up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Contralateral Esophagus Sparing Technique (CEST)
Arm/Group Description	IMRT with CEST and concurrent chemotherapy (any standard-of-care regimen) Contralateral Esophageal Sparing Technique (CEST): Determine whether CEST decreases rate of severe acute esophagitis
Measure Participants	26
Number [locoregional tumor failures]	0

5. Secondary Outcome

Title	Overall Survival Rate
Description	Follow-up time will be calculated from the date of registration to the date of death or the last follow-up date on which the patient was reported alive. Overall survival rates will be estimated using the Kaplan-Meier method.
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Contralateral Esophagus Sparing Technique (CEST)
Arm/Group Description	IMRT with CEST and concurrent chemotherapy (any standard-of-care regimen) Contralateral Esophageal Sparing Technique (CEST): Determine whether CEST decreases rate of severe acute esophagitis
Measure Participants	26
Number (95% Confidence Interval) [percentage of participants]	67 257.7%

Adverse Events

Time Frame	From the start of treatment up to 2 years
Adverse Event Reporting Description	Serious adverse events were defined as adverse events with a grade of 3 or higher that were deemed to be possibly, probably, or definitely related to treatment.
Arm/Group Title	Contralateral Esophagus Sparing Technique (CEST)
Arm/Group Description	IMRT with CEST and concurrent chemotherapy (any standard-of-care regimen) Contralateral Esophageal Sparing Technique (CEST): Determine whether CEST decreases rate of severe acute esophagitis
All Cause Mortality
	Contralateral Esophagus Sparing Technique (CEST)
	Affected / at Risk (%)	# Events
Total	1/26 (3.8%)
Serious Adverse Events
	Contralateral Esophagus Sparing Technique (CEST)
	Affected / at Risk (%)	# Events
Total	21/26 (80.8%)
Blood and lymphatic system disorders
Hyperglycemia	1/26 (3.8%)
Lymphocyte count decreased	19/26 (73.1%)
Anemia	1/26 (3.8%)
Neutrophil count decreased	11/26 (42.3%)
white blood cell count decreased	8/26 (30.8%)
Leukocytosis	1/26 (3.8%)
Cardiac disorders
Ventricular Tachycardia	1/26 (3.8%)
Heart Failure	1/26 (3.8%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/26 (3.8%)
Dyspnea	1/26 (3.8%)
Other (Not Including Serious) Adverse Events
	Contralateral Esophagus Sparing Technique (CEST)
	Affected / at Risk (%)	# Events
Total	18/26 (69.2%)
Blood and lymphatic system disorders
Hyponatremia	1/26 (3.8%)
Cardiac disorders
Atrial Fibrillation	2/26 (7.7%)
Gastrointestinal disorders
Gerd	1/26 (3.8%)
Dysphagia	3/26 (11.5%)
Nausea	1/26 (3.8%)
Dyspepsia	3/26 (11.5%)
Oral Thrush	1/26 (3.8%)
General disorders
Fatigue	6/26 (23.1%)
Psychiatric disorders
Anxiety	1/26 (3.8%)
Respiratory, thoracic and mediastinal disorders
Esophagitis	8/26 (30.8%)
Pneumonitis	2/26 (7.7%)
Dyspnea	4/26 (15.4%)
Pneumonia	1/26 (3.8%)
Hoarseness	1/26 (3.8%)
Skin and subcutaneous tissue disorders
Pruritus	2/26 (7.7%)
Dermatitis Radiation	5/26 (19.2%)
Erythema	1/26 (3.8%)

Limitations/Caveats

This protocol received IRB approval on 7/20/21 to remove secondary outcome "Median Survival Time" so this pre-specified outcome was subsequently deleted from the CT.gov record. The reason is that the secondary outcome of median survival time was not reached at time of analysis and final publication.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.