Hypofractionated Proton Beam Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With Stage II-III Non-Small Cell Lung Cancer

A Phase I Study of Radiation Dose Intensification With Accelerated Hypofractionated Proton Therapy and Chemotherapy for Non-small Cell Lung Cancer

This phase I trial studies the side effects and best dose of hypofractionated proton beam radiation therapy when given together with paclitaxel and carboplatin in treating patients with stage II-III non-small cell lung cancer. Proton beam radiation therapy is a type of radiation therapy that uses streams of protons (tiny particles with a positive charge) to kill tumor cells. Giving proton beam radiation therapy at higher doses over fewer days (hypofractionation) may improve local control of the tumor. Giving hypofractionated proton beam radiation therapy with chemotherapy may be a better treatment for non-small cell lung cancer

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Carboplatin; Drug: Paclitaxel; Radiation: Proton beam radiation therapy (PBT)

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

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:

1. Histologically or cytologically proven diagnosis of non-small cell lung cancer.

2. Clinical AJCC stage II-III (AJCC, 7th ed.) with plans to be treated with concurrent chemoradiotherapy.

   1. Recurrent non-small cell lung cancer is allowed, provided the intent of the current treatment is curative and there has been no prior radiation to the thorax.
   2. Prior chemotherapy, immunotherapy, or targeted therapy is permitted as long as patients have recovered from prior toxicities to grade ≤ 1

3. Appropriate stage for protocol entry based upon the following minimum diagnostic workup:

   1. History/physical examination within 30 days prior to registration;
   2. FDG-PET/CT scan for staging within 60 days prior to registration;
   3. MRI scan with contrast of the brain (preferred) or CT scan of the brain with contrast within 60 days prior to registration.
4. Zubrod Performance Status 0-2 within 30 days prior to registration.
5. Age ≥ 18 years.

6. CBC/differential obtained within 30 days prior to registration, with adequate bone marrow function defined as follows:

   1. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
   2. Platelets ≥ 100,000 cells/mm3;
   3. Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.);
7. AST and ALT ≤ 1.5 upper limit of normal within 30 days prior to registration.
8. Total bilirubin ≤ 1.5 upper limit of normal within 30 days prior to registration.

9. Serum creatinine < 1.5 mg/dL or calculated creatinine clearance ≥ 50 mL/min within 30 days prior to registration estimated by the Cockcroft-Gault formula:

   Creatinine Clearance (male) = [(140 - age) x (wt in kg)] [(Serum Creatinine mg/dl) x (72)]

   Creatinine Clearance (female) = 0.85 x Creatinine Clearance (male)

10. Peripheral neuropathy ≤ grade 1 at the time of registration.
11. Presence of measurable or evaluable disease.
12. Negative serum or urine pregnancy test within 2 weeks prior to registration for women of childbearing potential.
13. Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study.
14. Able to understand and willing to sign an IRB-approved informed consent document.

Exclusion Criteria:

1. Severe, active comorbidity, defined as follows:

   1. Unstable angina, history of myocardial infarction and/or congestive heart failure requiring hospitalization within the last 6 months;
   2. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
   3. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration;
   4. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol;
   5. 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.
2. Prior radiotherapy to the thorax.
3. Currently receiving any other investigational agents.
4. Pregnant or breastfeeding.
5. Presence of a cardiac pacemaker (due to the risk created by the proton magnet).

Inclusion of Women and Minorities

Both men and women and members of all races and ethnic groups are eligible for this trial.

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: Treatment (PBT, paclitaxel, and carboplatin); CHEMORADIATION THERAPY: PBT daily 5 days a week over 3 weeks for a total of 15 fractions; Paclitaxel intravenously (IV) over 1 hour weekly for 3 weeks; Carboplatin intravenously (IV) over 30 minutes weekly for 3 weeks. CONSOLIDATION CHEMOTHERAPY (B=beginning 4-6 weeks after completion of radiation therapy, patients may receive): Paclitaxel IV over 1 hour on day 1; Carboplatin IV over 30 minutes on day 1; At the discretion of the treating physician; Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Other Names: CBDCA; Paraplatin®; Drug: Paclitaxel; Other Names: Taxol®; Abraxane®; Onxol®; Radiation: Proton beam radiation therapy (PBT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) of hypofractionated proton beam therapy (PBT) with chemotherapy	Common Terminology Criteria for Adverse Events version 4 (CTCAE) will be used. The MTD will be chosen as the dose that yields a posterior estimate of toxicity closest to 20% while being between 15% and 25%. Dose limiting toxicity will be defined as toxicity that occurs within 6 months from the start of treatment, is possibly, probably or definitely related to treatment, and is related to the following Grade 3-5 pericardial effusion, pericarditis, restrictive cardiomyopathy, hemorrhage (pulmonary or upper respiratory), excluding nose, larynx, or pharynx, brachial plexopathy, laryngeal nerve dysfunction, myelitis, phrenic nerve dysfunction , atelectasis (grade 4-5 only), pulmonary fistula, hypoxia (provided grade 3 is worse than baseline), obstruction/stenosis of the airway, pleural effusion, pneumonitis, pulmonary fibrosis Grade 4-5 dysphagia, esophagitis, esophageal fistula, obstruction, perforation, stricture/stenosis, ulcer, and hemorrhage Grade 4-5 skin Any grade 5	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute toxicities	Common Terminology Criteria for Adverse Events version 4 (CTCAE) will be used. Adverse events will be tabulated by type and grade.	Up to 6 months
Incidence of late toxicities as defined	Common Terminology Criteria for Adverse Events version 4 (CTCAE) will be used. Adverse events will be tabulated by type and grade.	Up to 1 year

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Cliff Robinson, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2014
• Primary Completion (Actual): August 23, 2016
• Study Completion (Actual): October 2, 2017

Study Registration Dates

• First Submitted: June 20, 2014
• First Submitted That Met QC Criteria: June 20, 2014
• First Posted (Estimate): June 24, 2014

Study Record Updates

• Last Update Posted (Actual): December 8, 2017
• Last Update Submitted That Met QC Criteria: December 6, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• 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; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: 201404047

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: Yes
• product manufactured in and exported from the U.S.: No