Clinical trial NCT02172846: Hypofractionated Proton Beam Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With Stage II-III Non-Small Cell Lung Cancer
Official title: A Phase I Study of Radiation Dose Intensification With Accelerated Hypofractionated Proton Therapy and Chemotherapy for Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2014-06-24
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum tolerated dose (MTD) of hypofractionated proton beam therapy (PBT) with chemotherapy
timeFrame: Up to 6 months
Secondary outcomes:
measure: Incidence of acute toxicities
timeFrame: Up to 6 months
measure: Incidence of late toxicities as defined
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Cliff Robinson, M.D.
role: PRINCIPAL_INVESTIGATOR
References: