Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Bevacizumab

Albumin-Bound Paclitaxel

Fosbretabulin

Combretastatin

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg)administered intravenously on Day 1 of a 21-day cycle for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) alone on Day 1 every 3 weeks until progression or until 12 months from randomization.

Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg), administered intravenously Day 1 of a 21-day cycle and fosbretabulin (60 mg/m2) on Days 7, 14, and 21 for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) on Day 1 and fosbretabulin on Days 1, 7 and 14 every 3 weeks until progression or until 12 months from randomization.

Arm 2 only: Fosbretabulin (60 mg/m2) on Days 7,14 and 21 for 6 cycles.

Chemotherapy: Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles.

Chemotherapy: Paclitaxel (20 mg/m2) on Day 1 of each 21-day cycle for 6 cycles.

Bevacizumab (15 mg/kg) on Day 1 of each 21-day cycle for 6 cycles.

Jai Balkissoon, MD, FACS

The purpose of this study is to determine the safety, tolerability and efficacy of combretastatin A4 phosphate (CA4P), also known as fosbretabulin, in combination with bevacizumab (Avastin), carboplatin and paclitaxel in patients with chemotherapy naïve non-small cell lung cancer (NSCLC). This is a randomized parallel arm study. All participants will receive carboplatin, paclitaxel and bevacizumab, and half will additionally receive CA4P. Patients who complete the first 6 cycles of therapy and have not experienced disease progression will receive maintenance therapy with bevacizumab alone or with bevacizumab plus CA4P.

The rationale for this study is the potential additive or synergistic actions of vascular disrupting agents like CA4P with anti-angiogenic agents like bevacizumab.

Lung cancer has become the leading cause of cancer death in both men and women in the US and Europe, accounting for 29% of all cancer deaths. Non-Small Cell Lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases. Currently, no curative treatment is available for advanced stages of the disease (stages III and IV), which comprise the majority of cases. Treatment with the combination of carboplatin and paclitaxel has been shown to be effective and well tolerated in advanced stage NSCLC. Targeted therapies, such as bevacizumab, often act synergistically with chemotherapy. Bevacizumab inhibits vascular endothelial growth factor (VEGF), necessary for endothelial cell proliferation and new blood vessel formation. CA4P targets existing abnormal vasculature of tumors, impeding tumor blood flow and leading to extensive tumor cell death as a consequence of oxygen and nutrient deprivation.

This study will compare the effect of CA4P when combined with chemotherapy and bevacizumab on progression free survival (PFS) to PFS after chemotherapy and bevacizumab alone.

A Safety and Efficacy Study of Carboplatin, Paclitaxel, Bevacizumab and CA4P in Non-Small Cell Lung Cancer

A Phase II Study to Assess the Safety and Efficacy of the Combination of Carboplatin, Paclitaxel, and Bevacizumab ± Combretastatin A4 Phosphate (CA4P) Followed by Bevacizumab ± CA4P in Subjects With Chemotherapy Naïve Stage IIIB/IV Non-Squamous Cell Histology Non-Small Cell Lung Cancer (NSCLC)

Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0. Based on 20% increase of the longest diameter of target lesions or appearance of one or more new non-target lesions or/and progression of non-target lesions since the treatment started.

Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 for target lesions (assessed by MRI or CT scan): Complete Response (CR) is defined as the disappearance of all target lesions, Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, Progressive Disease is defined as at least 20% increase in the sum of the longest diameter of target lesions, Stable Disease (SD) is defined as neither shrinkage to qualify for a PR or increase to qualify for a PD.

Mateon Therapeutics

Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg)administered intravenously on Day 1 of a 21-day cycle for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) alone on Day 1 every 3 weeks until progression or until 12 months from randomization.

Carboplatin: Chemotherapy: Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles.

Paclitaxel: Chemotherapy: Paclitaxel (20 mg/m2) on Day 1 of each 21-day cycle for 6 cycles.

Bevacizumab: Bevacizumab (15 mg/kg) on Day 1 of each 21-day cycle for 6 cycles.

Arm 1: Chemotherapy+Bevacizumab

Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg), administered intravenously Day 1 of a 21-day cycle and fosbretabulin (60 mg/m2) on Days 7, 14, and 21 for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) on Day 1 and fosbretabulin on Days 1, 7 and 14 every 3 weeks until progression or until 12 months from randomization.

Fosbretabulin: Arm 2 only: Fosbretabulin (60 mg/m2) on Days 7,14 and 21 for 6 cycles.

Carboplatin: Chemotherapy: Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles.

Paclitaxel: Chemotherapy: Paclitaxel (20 mg/m2) on Day 1 of each 21-day cycle for 6 cycles.

Bevacizumab: Bevacizumab (15 mg/kg) on Day 1 of each 21-day cycle for 6 cycles.

Arm 2: Active Comparator+Fosbretabulin

Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) administered intravenously on Day 1 of a 21-day cycle for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) alone on Day 1 every 3 weeks until progression or until 12 months from randomization.

Carboplatin: Chemotherapy: Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles.

Paclitaxel: Chemotherapy: Paclitaxel (20 mg/m2) on Day 1 of each 21-day cycle for 6 cycles.

Bevacizumab: Bevacizumab (15 mg/kg) on Day 1 of each 21-day cycle for 6 cycles.

Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg), administered intravenously Day 1 of a 21-day cycle and fosbretabulin (60 mg/m2) on Days 7, 14, and 21 for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) on Day 1 and fosbretabulin on Days 1, 7 and 14 every 3 weeks until progression or until 12 months from randomization.

Fosbretabulin: Arm 2 only: Fosbretabulin (60 mg/m2) on Days 7, 14 and 21 for 6 cycles.

Carboplatin: Chemotherapy: Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles.

Paclitaxel: Chemotherapy: Paclitaxel (20 mg/m2) on Day 1 of each 21-day cycle for 6 cycles.

Bevacizumab: Bevacizumab (15 mg/kg) on Day 1 of each 21-day cycle for 6 cycles.

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

0 - Fully active

1 - Restricted in physically strenuous activity

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

Surgery Performed

Prior Surgery Due to NSCLC

Information Missing

Subject Given Radiation Therapy

Prior Radiation Due to NSCLC

IIIB

Stage of Disease at Study Entry

Chief Executive Officer

Complete Response

Partial Response

Stable Disease

Progressive Disease

Unknown

Best Overall Tumor Response Rate (RR) in the Intent-to-Treat Population

Overall Survival (OS) Using a Multivariate Cox Regression Model in the Intent-to-Treat Population

Progression Free Survival (PFS) in the Intent-to-Treat Population

ALT - Grade 3

ALT - Grade 4

AST - Grade 3

AST - Grade 4

ALP - Grade 3

ALP - Grade 4

Total Bilirubin - Grade 3

Total Bilirubin - Grade 4

Glucose - Grade 3

Glucose - Grade 4

Creatinine - Grade 3

Creatinine - Grade 4

Calcium - Grade 3

Calcium - Grade 4

Magnesium - Grade 3

Magnesium - Grade 4

Phosphorus - Grade 3

Phosphorus - Grade 4

Potassium - Grade 3

Potassium - Grade 4

Sodium - Grade 3

Sodium - Grade 4

Chemistry NCI-CTCAE Toxicity Grade of 3 or 4 (Safety Population)

Hemoglobin - Grade 3

Hemoglobin - Grade 4

White Blood Cell - Grade 3

White Blood Cell - Grade 4

Absolute Neutrophils - Grade 3

Absolute Neutrophils - Grade 4

Platelets - Grade 3

Platelets - Grade 4

Hematology NCI-CTCAE Grade 3 or 4 (Safety Population)

INR - Grade 3

INR - Grade 4

PTT - Grade 3

PTT - Grade 4

Coagulation NCI-CTCAE Grade 3 or 4 (Safety Population)

Overall Study

Symptoms and General Pathology

Rare Diseases

Neoplasm Metastasis

Neuroendocrine Tumors

Disease Progression

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Anti-Infective Agents

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

everolimus

fosbretabulin

Lowell Anthony, MD

This is a single center, open label, phase I study involving grade I-III gastroenteropancreatic neuroendocrine tumors, consisting of a dose escalation Part A followed by an expansion cohort Part B. On Part A Patients will be treated with daily oral everolimus. Fosbretabulin will be administered IV either q3 weekly or q weekly based on PO CRM cohort. Part B: Once the investigators have established an MTD in Part A, the investigators will be treating 15 more patients at that dose combination. The primary and secondary objectives of the expansion cohort will be similar to Part A of the study, i.e., to establish a safety profile of the experimental drug combination and to collect and assess efficacy data. Patients will be treated with concurrent everolimus and fosbretabulin for 12 weeks.

A variety of treatment options are available for NETs with carcinoid syndrome including surgical and medical therapies. Most subjects require somatostatin analogs to control the symptoms of carcinoid syndrome. Subjects who no longer respond to somatostatin and other liver-directed therapies, who experience progression of disease and increasing symptoms have limited options, including participation in a clinical trial. Recently everolimus and sunitinib have been approved for the treatment of subjects with progressive locally advanced or metastatic neuroendocrine tumors. Based on the preclinical data in models of NETs and the clinical activity seen in NETS and other tumor types that have existing tumor vascculature, this study will examine the effectiveness of fosbretabulin given in combination with everolimus in subjects with GI-NETs and PNETs.The vasoconstrictive effect of fosbretabulin is potent, though short-lived (4-8 hours), with no cumulative adverse effect. Everolimus inhibits angiogenesis, slows tumor growth and has a prolonged half-life (30 hours). Combining these two agents with distinctly different mechanisms of action may improve tumor control without additional toxicities, and has the potential of reducing drug resistance.

Fosbretabulin With Everolimus in Neuroendocrine Tumors With Progression

A Phase 1 Study of Fosbretabulin in Combination With Everolimus in Neuroendocrine Tumors (Grades 1-3) That Have Progressed After at Least One Prior Regimen for Metastatic Disease

To establish the maximum tolerated dose of the combination of everolimus plus fosbretabulin in neuroendocrine tumors (Grades 1-3) who have progressed after at least one prior regimen for metastatic disease.

Incidence of patients reporting at least one adverse event per NCI CTCAE v4.0

Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes.

Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Safety and Efficacy Study of Carboplatin, Paclitaxel, Bevacizumab and CA4P in Non-Small Cell Lung Cancer	NCT00653939	Tumors	Fosbretabulin Carboplatin Paclitaxel Bevacizumab	18 Years -	Mateon Therapeutics
Fosbretabulin With Everolimus in Neuroendocrine Tumors With Progression	NCT03014297	Neuroendocrine ... Everolimus	everolimus fosbretabulin	18 Years -	University of Kentucky
A Safety and Efficacy Study of Carboplatin, Paclitaxel, Bevacizumab and CA4P in Non-Small Cell Lung Cancer	NCT00653939	Tumors	Fosbretabulin Carboplatin Paclitaxel Bevacizumab	18 Years -	Mateon Therapeutics

Spots Global Cancer Trial Database for fosbretabulin