Phase II Study of Sorafenib + Carboplatin and Docetaxel in First Line Treatment of Stage IIIB/IV NSCLC

• ClinicalTrials.gov Identifier: NCT00647426
• Recruitment Status: Completed
• First Posted: March 31, 2008
• Results First Posted: October 22, 2019
• Last Update Posted: October 22, 2019
• Sponsor: Abramson Cancer Center of the University of Pennsylvania
• Information provided by (Responsible Party): Abramson Cancer Center of the University of Pennsylvania

Study Description

Brief Summary:

This is an open-label, single institution, phase II study of Sorafenib in combination with docetaxel and carboplatin in patients with advanced non-small cell lung cancer. Docetaxel and carboplatin will be given on day 1 of every three week cycle. Patients will take Sorafenib twice a day on the 1st day of treatment and continue to take the medication every day until progression of disease, prohibitive toxicity, or patient withdrawal from the study. Chemotherapy courses will repeat every 21 days in the absence of disease progression or unacceptable toxicity for a total of four cycles.

Condition or disease	Intervention/treatment	Phase
Non-Small Cell Lung Cancer	Drug: Sorafenib + Docetaxel/Carboplatin	Phase 2

Detailed Description:

Patients will be monitored after every two cycles (6 weeks) for tumor response, stability, or progression by radiographic imaging studies. The primary goal of this study is to determine the clinical response rate of this regimen in patients with advanced lung cancer. Secondary endpoints include time to progression, overall survival, and toxicity. Blood levels of ERK-phosphorylation, activated caspase 3, cyclin D1, anti -cIAP2, p-Akt, and Mcl1 activity will be measured at the beginning, middle and end of therapy to help identify predictors of drug response and toxicity during the first cycle of treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Sorafenib in Combination With Carboplatin and Docetaxel in the First Line Treatment of Stage IIIB/IV Non-Small Cell Lung Cancer
• Study Start Date: November 2007
• Actual Primary Completion Date: August 2011
• Actual Study Completion Date: December 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sorafenib + Docetaxel/Carboplatin; 400 mg po BID Sorafenib + 75 mg/m2 IV Docetaxel on day 1 plus AUC 6 on Carboplatin on day 1 of each 21 day cycle	Drug: Sorafenib + Docetaxel/Carboplatin; 400 mg po BID Sorafenib + 75 mg/m2 IV Docetaxel on day 1 plus AUC 6 on Carboplatin on day 1 of each 21 day cycle; Other Name: Carboplatin: Paraplatin, CBDCA

Outcome Measures

Primary Outcome Measures :

1. The Number of Patients With Stage IIIB/IV NSCLC Response Rate to the Combination Therapy of Sorafenib and Docetaxel/Carboplatin [ Time Frame: 30 months ]

   The response rate from the combination therapy of Sorafenib and Docetaxel/carboplatin for patients with Stage IIIB/IV NSCLC.The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria (see section 9.3.1).Tumor Response: Evaluation of target lesions Complete Response (CR): Disappearance of all target lesions Partial Response (PR): a) At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

   Progressive Disease (PD): a) At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Secondary Outcome Measures :

1. Number of Participants the Progression-free Survival (PFS) . [ Time Frame: 30 months ]
   Disease progression is based on RECIST documentation. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions
2. Number of Participants With Serious Adverse Events [ Time Frame: 30 months ]

   Assessment of adverse events related to the combination infusion, These include a Serious Adverse Event (SAE) is an adverse event occurring at any dose that results in any of the following outcomes:

   1. Death
   2. Life-threatening
   3. Persistent or significant disability/incapacity
   4. In patient hospitalization or prolongation of existing hospitalization

   5. Congenital anomaly/birth defect or • blood dyscrasia without inpatient hospitalization

      • convulsions without inpatient hospitalization
      • intensive treatment in an emergency room or at home for allergic bronchospasm without inpatient hospitalization
      • development of drug dependency
      • drug abuse
      • overdose with an associated serious event, or required intervention to prevent impairment/damage
3. The Number of Participants With Biomarkers of Sorafenib Activity and Toxicity [ Time Frame: 30 months ]
   Monitored at designated timepoints.All patients will be evaluable for toxicity from the time of their first treatment with SORAFENIB.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed NSCLC with clinical or radiological evidence of advanced disease (Stage IIIB/IV)
• Uni-dimensionally measurable disease
• Age => 18 years
• ECOG performance status of 0-1
• Life expectancy > 3 months

Exclusion Criteria:

• Small-cell or mixed histologies including a small cell component
• Prior chemotherapy, biotherapy, radiotherapy to an area of measurable disease
• Patients with peripheral neuropathy grade => 2

Contacts and Locations

Locations

United States, Pennsylvania

Abramson Cancer Center of University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Abramson Cancer Center of the University of Pennsylvania

Investigators

• Principal Investigator: Tracey Evans, MD; University of Pennsylvania

More Information

• Responsible Party: Abramson Cancer Center of the University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00647426 History of Changes
• Other Study ID Numbers: UPCC 12506
• First Posted: March 31, 2008
• Results First Posted: October 22, 2019
• Last Update Posted: October 22, 2019
• Last Verified: September 2019

Keywords provided by Abramson Cancer Center of the University of Pennsylvania:

Stage IIIB/IV

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carboplatin; Docetaxel; Sorafenib; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Protein Kinase Inhibitors; Enzyme Inhibitors