Study of Combination of Metronomic Oral Vinorelbine and Sorafenib in Patients With Advanced Non-small Cell Lung Cancer

NCT00870532 | Completed Phase 1

• 1 other identifier: 08-3-LUN
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

Targeting the blood supply of cancer, called anti-angiogenesis is a new but proven treatment strategy. There are two ways of achieving this effect. The first way to specifically target the molecular pathways that promote new blood vessel formation in cancer. An example of such an agent is sorafenib, which is an oral agent and which is already in use worldwide for the treatment of kidney and liver cancers. The second way is to target the cells lining the blood vessels by using low dose of chemotherapy agents administered at frequent intervals. This strategy is called metronomic chemotherapy. It is possible that combining agents like sorafenib and metronomic chemotherapy may further enhance anti-cancer effects. This study aims to determine the optimal way of combining oral vinorelbine in metronomic doses and sorafenib. Oral vinorelbine is a chemotherapy agent that is already approved for use in cancer treatment such as lung cancer. By combining both oral anti-cancer agents to optimize their anti-angiogenic effects in this study, the potential benefit to the patients can be tremendous and far-reaching. Special radiologic imagings and blood tests will be incorporated into this study to help further the understanding of the anti-angiogenic processes of both agents.

Conditions

Non-Small Cell Lung Cancer

Keywords

Phase I; Combination; Anti-angiogenic; Sorafenib; Metronomic oral vinorelbine

Outcome Measures

Primary Outcomes (1)

• to determine the optimal combination of metronomic oral vinorelbine with sorafenib to achieve anti-angiogenic and hence anti-tumour effect in patients with advanced NSCLC

  every 1-2 monthly with DCE-MR and circulating endothelial cells apart from routine CT scans

Secondary Outcomes (1)

• To determine the response rate to the combination of metronomic oral vinorelbine and sorafenib in advanced NSCLC

  CT scan every 2 months while on treatment

Study Arms (3)

1

EXPERIMENTAL

60 mg/week of vinorelbine + sorafenib

Drug: oral vinorelbine; Drug: sorafenib

2

EXPERIMENTAL

90 mg/week of vinorelbine + sorafenib

Drug: oral vinorelbine; Drug: sorafenib

3

EXPERIMENTAL

120 mg/week of vinorelbine + sorafenib

Drug: oral vinorelbine; Drug: sorafenib

Interventions

oral vinorelbine DRUG

The patients will be divided into 3 cohorts (15 patients per cohort), each cohort receiving a fixed metronomic (thrice a week) dose of oral vinorelbine at 60 mg/week, 90 mg/week, and 120 mg/week respectively. We should arrive at 3 different MTDs from the 3 cohorts.

Also known as: Navelbine Oral

1; 2; 3

sorafenib DRUG

Each patient within each cohort will receive a starting dose of sorafenib at 200 mg bid for 4 weeks. In the absence of dose-limiting toxicities, the dose of sorafenib will be escalated to 400 mg bid for another 4 weeks, 600 mg bid for 4 weeks and then finally 800 mg bid. We should arrive at 3 different MTDs from the 3 cohorts.

Also known as: Nexavar

1; 2; 3

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed NSCLC
• At least one or 2 prior lines of chemotherapy, including oral EGFR tyrosine-kinase inhibitor for metastatic disease or locally advanced unresectable disease. There should be at least 4 weeks since prior chemotherapy or radiation therapy; patients who decline conventional chemotherapy or oral EGFR tyrosine-kinase inhibitor as salvage 2nd or 3rd line treatment are also eligible.
• Minimum body-surface area (BSA) of 1.4 m2 at point of recruitment. This is a safeguard against recruiting small-built patients who may experience adverse reaction on absolute dosing of oral vinorelbine. At this body surface area, the maximum dosing of oral vinorelbine at 120 mg/week is equivalent to 86 mg/m2/week for a patient with BSA of 1.4 m2.
• Age \>21 years
• ECOG performance status \<2 (Karnofsky \>60%)
• Patients must have normal organ and marrow function as defined here: leukocytes \>3,000/mcL, absolute neutrophil count \>1,500/mcL, platelet count \> 100,000/mcL, serum bilirubin within normal institutional limits, AST(SGOT)/ALT(SGPT) \<2.5 X upper limit of normal, and creatinine within normal institutional limits or creatinine clearance \>60 mL/min/1.73 m2 for patients. These tests must be done within 1 week of study treatment.
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients receiving any other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Oral Vinorelbine or other agents used in study
• Prior and / or concomitant treatment with drugs known to induce or inhibit cytochrome P450 3A4: phenytoin, carbamazepine, barbiturates, rifampicin, imidazole antifungals (such as ketoconazole, fluconazole, itraconazole, metronidazole), omeprazole and ritonavir. Patients who are taking gastric acid-lowering agents such as H2 antagonist or antacids will be evaluated regarding the need to continue with these medications. If discontinuation of these medications is medically contraindicated, the patient will be excluded as these agents are known to lower the solubility of sorafenib and hence may limit their efficacy.
• Significant malabsorption syndrome or disease affecting the gastro-intestinal tract function
• Significant peripheral or autonomic neuropathy affecting sensation or bowel motility
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Uncontrolled hypertension defined as systolic blood pressure \>150 mmHg or diastolic pressure \>90 mmHg despite optimal management
• Pregnancy or breast-feeding or women of childbearing potential not using effective contraception
• Evidence or history of bleeding diathesis or coagulopathy
• Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months
• Pulmonary hemorrhage/bleeding event \>CTCAE grade 2 within 4 weeks of recruitment
• Any other hemorrhage/bleeding event \>CTCAE grade 3 within 4 weeks of recruitment

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead

Study Sites (1)

National Cancer Centre, Singapore

Singapore, 169610, Singapore

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Vinorelbine; Sorafenib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Eng-Huat Tan, MD

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant

Study Record Dates

• First Submitted: June 9, 2008
• First Posted: March 27, 2009
• Study Start: June 1, 2008
• Primary Completion: August 1, 2013
• Study Completion: September 1, 2013
• Last Updated: November 4, 2013

Record last verified: 2013-11

Locations

SG (1)