Cisplatin/Etoposide/Radiotherapy Followed by Consolidation Sorafenib for Inoperable Stage III Non-Small Cell Lung Cancer

A Phase II Trial of Concurrent Cisplatin/Etoposide/Radiotherapy Followed by Consolidation Sorafenib in Patients With Inoperable Stage III Non-Small Cell Lung Cancer (NSCLC): Hoosier Oncology Group LUN06-107

Sorafenib has demonstrated in vivo anti-tumor efficacy. This trial will evaluate the safety and preliminary efficacy of sorafenib following chemoradiation in locally advanced NSCLC.

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Cisplatin; Drug: Etoposide; Procedure: Radiotherapy; Drug: Sorafenib

Detailed Description

Outline: This is a multi-center study.

Chemotherapy/radiation therapy (2 cycles)

• Cisplatin 50 mg/m2 IV days 1 and 8 of 28 day cycle
• Etoposide 50 mg/m2 IV days 1-5 of 28 day cycle
• Concurrent chest radiation (planned dose is 5940 cGy with an additional, optional boost of 1080 cGy to a total allowed dose of 7020 cGy) with the following:

Maintenance therapy of Sorafenib 400 mg PO BID of 28 day cycle, to begin a minimum of 6 and maximum of 9 weeks from completion of chemo-radiotherapy until PD, intolerable toxicity, or up to 1 year.

Patients with progressive disease will discontinue treatment.

ECOG performance status 0 or 1

Hematopoietic:

• Absolute neutrophil count (ANC) ≥ 1500 mm3
• Platelet count ≥ 100,000 mm3
• Hemoglobin ≥ 9 g/dL
• PT or INR < 1.5 x ULN unless on anti-coagulant therapy
• PTT < 1.5 x ULN unless on anti-coagulant therapy

Hepatic:

• Bilirubin ≤ 1.5 x ULN
• ALT ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement)
• AST ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement)

Renal:

• Creatinine < 1.5 X upper limit of normal (ULN)

Cardiovascular:

• No significant history of cardiac disease: Congestive heart failure > class II NYHA.
• Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within 90 days prior to registration for initial therapy) or myocardial infarction within 6 months prior to registration for initial therapy.

Respiratory:

• FEV1 ≥ 1 liter by spirometry within 60 days prior to registration for initial therapy.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Galesburg, Illinois, United States, 61401
      • Medical & Surgical Specialists, LLC
  • Indiana
    • Fort Wayne, Indiana, United States, 46815
      • Fort Wayne Oncology & Hematology, Inc
    • Goshen, Indiana, United States, 46527
      • Center for Cancer Care at Goshen Health System
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Cancer Center
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Center
    • Muncie, Indiana, United States, 47303
      • Medical Consultants, P.C.
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research Consortium
  • Ohio
    • Cincinnati, Ohio, United States, 45247
      • Oncology Partners Network

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:

• Histological or cytological proof of non-small cell lung cancer (NSCLC).
• Measurable or non-measurable disease per RECIST.
• Unresectable Stage IIIA or IIIB disease as evaluated by imaging.
• Must be age ≥ 18 years at the time of consent.
• Written informed consent and HIPAA authorization for release of personal health information.
• Females of childbearing potential and males must be willing to use an effective method of contraception.
• Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for initial therapy.

Exclusion Criteria:

• No prior chemotherapy or radiotherapy for lung cancer.
• No positive supraclavicular or scalene lymph nodes extending up into the cervical region.
• No superior sulcus (pancoast tumors).
• No malignant pleural effusions. The only exception is a patient with a pleural effusion visible only on CT scan (and not visible on CXR) OR deemed too small to tap.
• No clinically significant or malignant pericardial effusions.
• No CNS metastases.
• No unintended weight loss (> 5% body weight) in the preceding 90 days prior to registration for initial therapy.
• No treatment with any investigational agent within 30 days prior to being registered for initial therapy.
• No prior therapy with a Ras pathway inhibitor or anti-angiogenic agent.
• No other active cancers.
• Females must not be breastfeeding.
• No active clinically serious infections as judged by the treating investigator (> CTC v3, Grade 2) including known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• No major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration for initial therapy.
• No anticipation of need for major surgical procedure during the course of the study.
• No minor surgical procedures such as fine needle aspirations or cone biopsies within 7 days prior to registration for initial therapy.
• No history of allergic reactions to drugs utilizing the vehicle polysorbate 80 + polyethylene glycol (etoposide).
• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to registration for initial therapy.
• No use inhibitors or inducers of the cytochrome p450 system CYP3A4 enzyme or other medications such as aprepitant, ketoconazole, itraconazole, quinidine, digoxin, cyclosporine, ritonavir, grapefruit products, St. John's Wort, rifampin (rifampicin), carbamazepine, phenytoin, dexamethasone, and phenobarbital.
• No evidence or history of bleeding diathesis or coagulopathy.
• No serious non-healing wound, ulcer, or bone fracture.
• No known or suspected allergy to sorafenib.
• No uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal medical management.
• No thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within 6 months prior to registration for initial therapy.
• No pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks prior to registration for initial therapy.
• No hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to registration for initial therapy.
• No condition that impairs patient's ability to swallow whole pills or any malabsorption problem.

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: Investigational Treatment; Cisplatin/Etoposide/Radiotherapy followed by Sorafenib in patients with inoperable stage III non-small cell lung cancer

Drug: Cisplatin; Cisplatin 50 mg/m2 IV, days 1 and 8 of 28 day cycle; Drug: Etoposide; Etoposide 50 mg/m2 IV, days 1-5 of 28 day cycle; Procedure: Radiotherapy; Concurrent chest radiation (planned dose is 5940 cGy with an additional, optional boost of 1080 cGy to a total allowed dose of 7020 cGy); Drug: Sorafenib; Maintenance therapy of Sorafenib 400 mg PO BID, to begin a minimum of 6 and maximum of 9 weeks from completion of chemo-radiotherapy until PD, intolerable toxicity, or up to 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to Disease Progression (TTP)	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	18 months

Collaborators and Investigators

• Sponsor: Nasser Hanna, M.D.
• Collaborators: Bayer; Amgen; Walther Cancer Institute
• Investigators: Study Chair: Nasser Hanna, M.D., Hoosier Oncology Group, LLC

Publications and helpful links

Helpful Links

• Hoosier Cancer Research Network Website

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: December 28, 2006
• First Submitted That Met QC Criteria: December 28, 2006
• First Posted (Estimate): December 29, 2006

Study Record Updates

• Last Update Posted (Estimate): July 25, 2016
• Last Update Submitted That Met QC Criteria: June 13, 2016
• Last Verified: May 1, 2016

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; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Protein Kinase Inhibitors; Etoposide; Cisplatin; Sorafenib
• Other Study ID Numbers: HOG LUN06-107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES