Pulsed Low Dose Rate Radiation With Concurrent Chemotherapy for Non-Small Cell Lung Cancer and Esophageal Cancer

Phase I study with the hypothesis that Pulsed Low Dose Radiation (PLDR) radiation delivery technique can significantly decrease the rate of severe acute esophagitis in patients receiving concurrent Chemo-radiation therapy (CRT) for non-small cell lung cancer or esophageal cancer while maintaining similar efficacy. For these patients, the rate of severe acute esophagitis during concurrent CRT is high (approximately 20%) when conventional external beam radiation is utilized. Severe acute esophagitis can cause many adverse consequences such as severe discomfort, weight loss, hospitalization, interruption/early termination of treatment, and worse surgical complications for those who receive surgery after CRT. PLDR radiation has the potential to maintain the tumor control rates of conventional radiation while decreasing the toxicity to the surrounding normal tissue 29-35.

We have completed accrual to a phase I PLDR radiation study, in which patient received palliative re-irradiation with PLDR technique for their metastatic disease in previous irradiated field. In that phase I study, PLDR demonstrated safety for acute toxicities in the setting of re-irradiation for a total dose of 50 Gy, with analysis of 60 Gy pending. The follow up time for that phase I study is limited as most enrolled patients have short overall survival due to their terminal illness.

This proposed phase I study is, to our knowledge, the first clinical study with combination of PLDR radiation and concurrent chemotherapy for definitive treatment.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer; Lung Cancer
• Intervention / Treatment: Radiation: Pulsed Low Dose Radiation; Drug: Carboplatin; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Joshua Meyer, MD; Phone Number: 215-214-1515; Email: joshua.meyer@fccc.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
      • Contact: Joshua Meyer, MD; Phone Number: 215-214-1515; Email: joshua.meyer@fccc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient must have pathologically-confirmed and previously untreated:

   • Non-small cell lung cancer, Stage IIIA (T1-3 N2 M0); OR
   • Localized esophageal cancer, ≥T2, or N+, and M0 according to the American Joint Committee on Cancer (AJCC) 7th edition staging.
2. The planned treatment regimen must be concurrent chemoradiation with Carboplatin-Paclitaxel followed by surgery.
3. Age > 18 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status is 0-1.

5. Laboratory studies must meet each of the following criteria (with labs drawn within 4 weeks prior to the registration):

   • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
   • Platelets ≥100,000 cells/mm3
   • Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable)
   • Creatinine ≤2 X the upper limit of normal
   • Bilirubin ≤ 1.5 X upper limit of normal
   • Aspartate transaminase (AST) ≤ 3 X upper limit of normal
6. Men and women of childbearing potential must be willing to exercise an effective form of birth control (abstinence/contraception) while on study and for 3 months after therapy completed.
7. Patients must be able to read and write English to comply with the questionnaire portions of the protocol.
8. Subjects must sign a written informed study consent and HIPAA consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.

Exclusion Criteria:

1. Patients who have had previous radiotherapy in the thorax.
2. Patients who have a history of ataxia telangiectasia or other documented history of radiation hypersensitivity.
3. Patients who have a history scleroderma or other active connective tissue disease.
4. Women of childbearing potential must not be pregnant with a negative urine pregnancy test within 72 hours prior to registration and non-lactating; postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential; woman status post oophorectomy or hysterectomy are considered non-childbearing potential
5. Patients who have uncontrolled inter-current illness including, but not limited to, psychiatric illness/social situations that would limit compliance with study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pulsed Low dose radiation with Carboplatin/Paclitaxel; Pulsed Low Dose Radiation concurrent with Carboplatin and Paclitaxel

Radiation: Pulsed Low Dose Radiation; Treatment naïve patients with non-small cell lung cancer or esophageal cancer whose planned treatment regimen is concurrent CRT followed by surgery. The total radiation dose will be 50.4 Gy in daily fraction of 1.8 Gy for esophageal cancer and 60 Gy in daily fraction of 2 Gy for non-small cell lung cancer. The concurrent chemo regimen will carboplatin-paclitaxel managed by the treating medical oncologist. Patients are planned to receive surgery at approximately 6 to 9 weeks after finishing CRT with surgical aspects determined by the treating surgical oncologist.; Drug: Carboplatin; Treatment naïve patients with non-small cell lung cancer or esophageal cancer whose planned treatment regimen is concurrent CRT followed by surgery. The total radiation dose will be 50.4 Gy in daily fraction of 1.8 Gy for esophageal cancer and 60 Gy in daily fraction of 2 Gy for non-small cell lung cancer. The concurrent chemo regimen will carboplatin-paclitaxel managed by the treating medical oncologist. Patients are planned to receive surgery at approximately 6 to 9 weeks after finishing CRT with surgical aspects determined by the treating surgical oncologist.; Drug: Paclitaxel; Treatment naïve patients with non-small cell lung cancer or esophageal cancer whose planned treatment regimen is concurrent CRT followed by surgery. The total radiation dose will be 50.4 Gy in daily fraction of 1.8 Gy for esophageal cancer and 60 Gy in daily fraction of 2 Gy for non-small cell lung cancer. The concurrent chemo regimen will carboplatin-paclitaxel managed by the treating medical oncologist. Patients are planned to receive surgery at approximately 6 to 9 weeks after finishing CRT with surgical aspects determined by the treating surgical oncologist.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of severe acute esophagitis in patients with lung cancer and esophageal cancer treated with concurrent CRT using PLDR technique.	The investigator will evaluate the severity of other adverse events using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.0).	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life	Quality of life will be evaluated based on a quality of life survey conducted at different time-points during the study. After entering in the study survey will be conducted in 1st month , 2nd month ,3rd month, 6th month, 9th month. Number of surveys conducted will be the same however a delay due toxicity is possible and therefore last survey could be collected up to 12 months.	1 year
Progression free survival	progression free survival will be evaluated from the day of first treatment until disease progression	1-5 years
Response rate based	Response rate will be evaluated based on the outcome of surgical pathology	1 year

Collaborators and Investigators

• Sponsor: Fox Chase Cancer Center
• Investigators: Principal Investigator: Joshua Meyer, MD, Fox Chase Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2017
• Primary Completion (Anticipated): May 1, 2024
• Study Completion (Anticipated): May 1, 2025

Study Registration Dates

• First Submitted: March 23, 2017
• First Submitted That Met QC Criteria: March 23, 2017
• First Posted (Actual): March 29, 2017

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Head and Neck Neoplasms; Esophageal Diseases; Lung Neoplasms; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: RT-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No