Proton Radiation Therapy With Cisplatin and Etoposide Followed by Surgery in Stage III Non-Small Cell Lung Cancer

A Phase I Trial of Hypofractionated Proton Radiation Therapy With Cisplatin and Etoposide Followed by Surgery in Stage III Non-Small Cell Lung Cancer

This research study is looking at an alternative way of delivering radiation therapy with protons. Protons are tiny particles with a positive charge that can be controlled to travel a certain distance and stop inside the body. In theory, this allows better control of where the radiation dose is delivered as compared to photons. Information from other research studies suggests that proton radiation may help to reduce unwanted side effects from radiation and allow an increase in radiation dose that increase the odds of tumor killing.

The purpose of this study is to determine the safest dose of proton radiation therapy to give in combination with standard chemotherapy in participants with Non-Small Cell Lung Cancer (NSCLC).

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Radiation: Proton Beam Radiation; Drug: Cisplatin; Drug: Etoposide

Detailed Description

Proton radiation will be delivered daily Monday through Friday for 5 weeks. Study therapy will be give as an outpatient at the Francis H. Burr Proton Center at Massachusetts General Hospital.

During the weeks that subjects receive radiation, they will also receive 2 cycles of chemotherapy. Each cycle will last 28 days.

Cisplatin will be give as an IV infusion over 30-60 minutes or 1-2 hours on Days 1 and 8 of Cycles 1 and 2.

Etoposide will be given as an IV infusion over 60 minutes on Days 1, 2, 3, 4, 5 of Cycles 1 and 2.

After radiation and 2 cycles of chemotherapy are completed, subjects may have surgery to remove their tumor.

Following surgery, subjects may receive another 2 cycles of chemotherapy (Cycles 3 and 4). Each cycles lasts 21 days. Cisplatin is given on Day 1. Etoposide is given on Days 1, 2, and 3.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02214
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed non-small cell lung cancer with a clinical stage of IIIA
• Candidate for chemoradiation and surgical resection
• Measurable disease
• Life expectancy > 6 months
• Normal organ and marrow function

Exclusion Criteria:

• Pregnant or breast-feeding
• Prior therapy for lung cancer with chemotherapy
• Prior chest radiation
• Compromised pulmonary function
• Severe neurovascular disease
• History of high cardiac risk including unstable angina
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin or etoposide
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive hear failure, unstable angina pectoris, clinically significant or serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• History of a different malignancy unless disease-free for at least 3 years and at low risk for recurrence. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, non muscle-invasive bladder cancer, basal cell or squamous cell carcinoma of the skin
• Subjects with HIV

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: Radiation, Chemotherapy and Surgery; Proton beam radiation, plus chemotherapy with cisplatin and etoposide, followed by surgery.	Radiation: Proton Beam Radiation; 45-55 Gy total, 1.8-2.2 Gy x 25 fractions Mon-Fri for 5 weeks; Drug: Cisplatin; 50 mg/m2 IV on days 1, 8 of cycles 1 and 2; Drug: Etoposide; 50 mg/m2 IV on days 1-5 on Cycles 1-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD	To establish the MTD of a proton beam-based regimen consisting of 25 fractions, together with concurrent standard cisplatin and etoposide chemotherapy followed by surgery +/- adjuvant chemotherapy for Stage III NSCLC, and to describe post-treatment surgical complications and treatment toxicity using CTCAE v4.0	1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Downstaging and Response	To describe pathological downstaging and response following preoperative proton radiation and cisplatin/etoposide chemotherapy	1.5 years
Biomarkers	To explore the predicitive value of biomarkers for radio- and chemosensitization in pre-treatment tumor biopsies and surgical specimens.	1.5 years
Tumor Control and Survival Rates	To evaluate local and regional tumor control rates, progression free survival (PFS) rates, and overall survival rates and 2 and 5 years	5 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Henning Willers, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: March 26, 2012
• First Submitted That Met QC Criteria: March 28, 2012
• First Posted (Estimate): March 29, 2012

Study Record Updates

• Last Update Posted (Estimate): February 17, 2016
• Last Update Submitted That Met QC Criteria: February 12, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Lung cancer; Stage III
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide; Cisplatin
• Other Study ID Numbers: 11-253