Proton Beam Radiation With Concurrent Chemotherapy and Nelfinavir for Inoperable Stage III Non Small Cell Lung Cancer (NSCLC)
This study is currently recruiting participants.
Verified February 2013 by Abramson Cancer Center of the University of Pennsylvania
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania
First received: April 12, 2010
Last updated: February 25, 2013
Last verified: February 2013
Seventy two patients are being asked to take part in this research study because they have been diagnosed with Stage IIIA or IIIB non-small cell lung cancer (NSCLC). This study is being done to determine the highest safe dose of proton beam radiotherapy and/or study drug (called Nelfinavir) that can be given with concurrent chemoradiotherapy to patients with cancer without causing bad side effects; and to develop biomarker for clinical outcome. This study will be done in two phases. In the first phase, feasibility will be established. We will follow patients treatment courses and record side effects at the standard proton radiation dose that can be given together with Cisplatinum + Etoposide or Carboplatin + Paclitaxel. In the second phase, we will see if it is possible to increase the total proton radiation dose or study drug without increasing the number of bad side effects while treated together with chemotherapy drugs.
Non Small Cell Lung Cancer
||Endpoint Classification: Efficacy Study
Primary Purpose: Treatment
||Phase I Dose Escalation Trial of Proton Beam Radiotherapy With Concurrent Chemotherapy and Nelfinavir for Inoperable Stage III NSCLC
Primary Outcome Measures:
- Feasibility [ Time Frame: 10 days of estimated date of treatment completion or requires a treatment break greater than 5 days ] [ Designated as safety issue: Yes ]
Feasibility will be based on multiple radiation planning and treatment parameters.Treatment will be deemed infeasible if patient cannot be given treatment because anatomy is such that a dosimetrically satisfactory treatment plan cannot be devised. Patient is unable to tolerate 30% of treatments using proton radiotherapy, that is, up to 70% of treatments could be delivered using photons. Patient is unable to complete all of his/her treatments within 10 days of estimated date of treatment completion or require a treatment break greater than 5 days.
- Acute Toxicity (or dose limiting toxicity) [ Time Frame: Greater than 14 days ] [ Designated as safety issue: Yes ]
Any treatment related Grade 4 hematologic toxicty requiring a break in therapy of greater than 14 days or Grade 3 or higher non-hematologic toxicity, except esophagitis and pneumonitis, which is observed within 90 days from start of radiotherapy and which is probably or definitely related to treatment. All toxicities will be graded by NCI CTC Version 4.0.
- Late Toxicity [ Time Frame: Open-Ended, Known to occur a year or more after therapy ] [ Designated as safety issue: Yes ]
Late toxicities will be graded according to the RTOG/EORTC late morbidity scoring system. The time frame for late toxicity is open-ended and late toxicities have been known to occur a year or more after therapy. Follow-up for late toxicity will cease when a patient experiences disease progression, since 2nd line therapies may then be initiated.
Secondary Outcome Measures:
- Clinical Efficacy [ Designated as safety issue: No ]
Defined as metabolic response (complete, partial or less than partial) based on PET/CT imaging. Patients are followed for disease recurrence and site (local, regional, distant). Progression-free and overall survival are defined as from start of treatment to first documented recurrence (for PFS), date of death or last patient contact alive.
- Biomarkers [ Designated as safety issue: No ]
Will be evaluated on tumor tissue, as the methods for measurement become available. For example, the radiation resistance biomarker, IRDS (Interferon Related DNA Damage Resistance Gene Signature), will soon be under prospective validation in NSCLC. Similar biomarker discoveries will be considered during the course of this 4 1/2.year trial.
| Estimated Enrollment:
| Study Start Date:
| Estimated Primary Completion Date:
||August 2014 (Final data collection date for primary outcome measure)
Two dose levels of Nelfinavir will be evaluated in each concurrent chemotherapy group (carboplatin/paclitaxel and cisplatin/etoposide) at the RPTD does of proton beam radiotherapy: 625 and 1250 mg PO bid.
- Determine MTD of proton beam radiotherapy with concurrent cisplatin and etoposide for stage III NSCLC.
- Determine MTD of proton beam radiotherapy with concurrent carboplatin and paclitaxel for stage III NSCLC in non-cisplatin candidates.
- Determine MTD of Nelfinavir with concurrent chemoradiotherapy for stage III NSCLC at RPTD of proton beam radiotherapy.
- Develop biomarker for clinical outcome with concurrent chemoradiotherapy in stage III NSCLC.
- To determine clinical efficacy, as defined by metabolic response, sites of recurrence (e.g., local, regional, distant) and progression-free and overall survival.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Histologically confirmed diagnosis of NSCLC.
- Stage IIIA or IIIB NSCLC.
- Patients must have no evidence of metastatic disease based on routine imaging.
- Patients must have a Karnofsky Performance Status of 60.
- Age 18 and older.
- Patients must be able to provide informed consent.
- Adequate bone marrow function (i.e. WBC larger than or equal to 4000/mm3, platelets larger than or equal to 100,000 mm3).
- Adequate renal function for cisplatin or carboplatin as determined by the medical oncologist: Usually Calculated creatinine clearance (CrCl) larger than or equal to 45 mL/min or serum creatinine level smaller than or equal to1.5 x institutional ULN.
- Patients must have bilirubin 1.5 mg/dl.
- Women of child-bearing potential as long as she agrees to use a recognized method of birth control (e.g. oral contraceptive, IUD, condoms or other barrier methods etc).
- Hysterectomy or menopause must be clinically documented.
- Prior or simultaneous malignancies within the past two years (other than cutaneous squamous or basal cell carcinoma or melanoma in situ).
- Pregnant women, women planning to become pregnant and women that are nursing.
- Actively being treated on any other research study.
- For the Nelfinavir phase of the trial only: Patients who are taking Antiarrhythmics (amiodarone, quinidine), Antimycobacterial (rifampin), Ergot Derivatives (dihydroergotamine, ergonovine, ergotamine, ethylergonovine), Herbal Products (St. John's wort/ hypericum perforatum), HMG-CoA Reductase Inhibitors (lovastatin, simvastatin), Neuroleptic (pimozide), Proton Pump Inhibitors, or Sedative/ Hypnotics (midazolam, triazolam). Note: Patients with the following conditions are deemed unsuitable for cisplatin-based chemotherapy (and will be treated with carboplatin): (a) Hearing impairment/ peripheral neuropathy Grade 1 or less at baseline (b) Symptomatic/uncontrolled congestive heart failure (unable to tolerate volume load with pre- and post-cisplatin hydration)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01108666
|Abramson Cancer Center of the University of Pennsylvania
|Philadelphia, Pennsylvania, United States, 19104 |
|Contact: Ramesh Rengan, MD 855-216-0098 PennCancerTrials@emergingmed.com |
Abramson Cancer Center of the University of Pennsylvania
No publications provided
||Abramson Cancer Center of the University of Pennsylvania
History of Changes
|Other Study ID Numbers:
|Study First Received:
||April 12, 2010
||February 25, 2013
||United States: Institutional Review Board
Keywords provided by Abramson Cancer Center of the University of Pennsylvania:
Adult subjects with a confirmed diagnosis of Stage IIIA or IIIB NSCLC, with adequate bone marrow, liver and renal function.
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 05, 2013
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action