Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Capecitabine

Doxorubicin

Liposomal doxorubicin

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antimetabolites

Tablets, Oral, Dose escalation to a MTD from a starting dose of 850 mg/m², twice a day (BID) x 14d per cycle, until disease progression

IV, Dose escalation to a MTD from a starting dose of 40 mg/m², Q3wks, until disease progression

IV, Dose Escalation to a MTD from a starting dose of 32 mg/m², Q3wks, until disease progression

Ixabepilone

IV, Dose escalation to an MTD from a starting dose of 60 mg/m², Q3wks, Until disease progression

IV, Dose escalation to an MTD from a starting dose of Paclitaxel 135 mg/m², Q3wks, Until disease progression

Tablets, Oral, Dose escalation to a MTD from a starting dose of 400 mg, daily (QD), until disease progression

Brivanib alaninate

Bristol-Myers Squibb

To determine safety and maximum tolerated dose of brivanib alaninate when administered in combination with capecitabine, doxorubicin, ixabepilone, docetaxel and paclitaxel chemotherapy to subjects with advanced or metastatic solid tumors

Ascending Multiple-Dose Study of Brivanib Alaninate in Combination With Chemotherapeutic Agents in Subjects With Advanced Cancers

A Phase I, Multi-arm, Dose Escalation Study of Brivanib Alaninate Combined With Several Chemotherapy Regimens in Subjects With Solid Tumors

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Uterine Cervical Neoplasms

Recurrence

Carcinoma

Adenocarcinoma

Carcinoma, Squamous Cell

Carcinoma, Adenosquamous

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

Patients receive brivanib alaninate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Brivanib Alaninate

Laboratory Biomarker Analysis

John K Chan

This phase II trial studies how well brivanib alaninate works in treating patients with cervical cancer that has come back. Brivanib alaninate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. To estimate the proportion of patients with persistent or recurrent cervical cancer, who survive progression-free for at least 6 months and the proportion of patients who have objective tumor response (complete or partial), treated with brivanib (brivanib alaninate).

II. To determine the nature and degree of toxicity of brivanib in this cohort of patients.

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival (PFS) and overall survival (OS) of patients with persistent or recurrent cervical cancer treated with brivanib.

TERTIARY OBJECTIVES:

I. To obtain the serum expression levels of surrogate markers of brivanib effects including angiogenic factors (vascular endothelial growth factor \[VEGF\] and basic fibroblast growth factor \[bFGF\]) and markers of endothelial damage (E-selectin, vascular cell adhesion molecule 1 \[VCAM-1\], and (intercellular adhesion molecule 1 \[ICAM-1\]). (exploratory) II. To determine whether these marker expression levels alone or in combination are associated with response, PFS, or overall survival. (exploratory)

OUTLINE:

Patients receive brivanib alaninate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Brivanib Alaninate in Treating Patients With Persistent or Recurrent Cervical Cancer

A Phase II Evaluation of Brivanib (BMS582664) in the Treatment of Persistent or Recurrent Carcinoma of the Cervix (BMS Study CA182-048)

Surrogate markers will be associated with response, PFS, and OS.

Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response assessed by RECIST 1.1

Proportion of participants who survive progression-free for at least 6 months without non-protocol therapy from study entry. Progression is assessed by RECIST 1.1.

Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v.4.0

Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1

Overall survival is defined as the duration of time from study entry to time of death or the date of last contact..

National Cancer Institute (NCI)

Gynecologic Oncology Group

Brivanib 800mg administered orally every day on days 1 to 28 of each cycle until disease progression or adverse effects prohibit further treatment. One cycle is 28 days.

Brivanib

30-39 years

40-49 years

50-59 years

60-69 years

70-79 years

Age, Customized

Sex/Gender, Customized

Linda Gedeon for Wei Deng,PhD

Objective Tumor Response

PFS for at Least 6 Months Without Non-protocol Therapy From Study Entry.

Leukopenia

Thrombocytopenia

Neutropenia

Anemia

Other Investigations

Cardiac Disorders

Gastrointestinal Disorders

General disorders & administration site conditions

Hepatobiliary Disorders

Infections and infestations

Metabolism and nutrition disorders

Musculoskeletal & connective tissue disorders

Neoplasms benign, malignant & unspecified

Nervous system disorders

Renal and urinary disorders

Vascular Disorders

Adverse Events (Grade 3 or Higher) During Treatment Period

Progression-free Survival

Overall Survival

Serum Expression Levels of Surrogate Markers of Brivanib Alaninate Effects Including Angiogenic Factors (VEGF and bFGF) and Markers of Endothelial Damage (E-selectin, VCAM-1, and ICAM-1)

Overall Study

Rare Diseases

Carcinoma, Transitional Cell

Cystadenocarcinoma, Serous

Adenocarcinoma, Clear Cell

Adenocarcinoma, Mucinous

Cystadenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Transitional Cell Carcinoma

Adenocarcinoma of the Appendix

Amino Acids

Mitogens

Tyrosine Kinase Inhibitors

Tyrosine

Matthew Powell

This phase II trial is studying how well brivanib alaninate works in treating patients with endometrial cancer that has come back (recurred) or is persistent. Brivanib alaninate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. To assess the activity of brivanib (brivanib alaninate) for patients with recurrent or persistent endometrial cancer with the frequency of patients who survive progression-free for at least 6 months after initiating therapy or have objective tumor response..

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival and overall survival. II. To determine the nature and degree of toxicity of brivanib as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v)3.0 in this cohort of patients.

TERTIARY OBJECTIVES:

I. To determine whether activating mutations in fibroblast growth factor receptor 2 (FGFR2) are associated with progression-free survival status \> 6 months following brivanib treatment, objective tumor response following brivanib treatment, or endometrioid histology.

II. To explore the associations between select biomarkers and response to brivanib (progression-free survival status \> 6 months and objective tumor response), measures of clinical outcome (progression-free survival and overall survival) or disease status including histologic cell type: i) mutations in FGFR2 or phosphatase and tensin homolog (PTEN) in deoxyribonucleic acid (DNA) from formalin-fixed and paraffin-embedded (FFPE) tumor or normal blood cells; ii) immunohistochemical (IHC) expression of the FGFR family and ligands, steroid receptor isoforms or phosphorylated (p) v-akt murine thymoma viral oncogene homolog 1 (AKT) in FFPE tumor; iii) concentration or the change in the concentration of vascular endothelial growth factor (VEGF) or type IV collagen in pre-cycle 1, pre-cycle 2 and/or pre-cycle 3 plasma.

III. To explore the relationship among the panel of biomarkers evaluated in this cohort: i) mutations in FGFR2 or PTEN; ii) IHC expression of the FGFR family and ligands, steroid receptor isoforms or pAKT; iii) concentration or the change in the concentration of VEGF or type IV collagen.

OUTLINE:

Patients receive brivanib alaninate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Brivanib Alaninate in Treating Patients With Recurrent or Persistent Endometrial Cancer

A Phase II Evaluation of Brivanib (BMS582664), an Oral, Multitargeted Growth Factor Tyrosine Kinase Inhibitor in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Will be correlated with clinical measures of outcome such as tumor response, progression-free survival (PFS), and endometrioid histology.

Will be correlated with PFS, OS, tumor response, and histologic cell type.

Will be correlated with PFS, overall survival (OS), tumor response, and histologic cell type.

Whether or not the patient survived progression-free for at least 6 months.

Per response evaluation criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>= 30 % decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.

Characterized graphically with Kaplan-Meier estimates and using descriptive statistics. The effect of cell type (type I versus type II endometrial cancers) on overall survival will be examined.

Characterized graphically with Kaplan-Meier estimates and using descriptive statistics. The effect of cell type (type I versus type II endometrial cancers) on progression-free survival will be examined.

Brivanib 800 mg orally every day (one cycle = 28 days) until disease progression or adverse effects prohibit further therapy.

Age, Continuous

20-29 years

80-89 years

Sex: Female, Male

Linda Gedeon For Michael Sill, PhD.

Progression-free Survival > 6 Months

Tumor Response

Duration of Overall Survival

Duration of Progression-free Survival

Cardiac

Coagulation

Constitutional

Dermatologic

Gastrointestinal

Genitourinary/Renal

Infection

Lymphatics

Metabolic

Musculoskeletal

Other Neurological

Pain

Vascular

Death, Not CTC coded

Severity of Adverse Events as Assessed by CTCAE v3.0 Criteria

Activating Mutation in FGFR2

Change in Concentration of VEGF and Type IV Collagen

IHC Expression of FGFR Family and Ligands, Steroid Receptor Isoforms, and pAKT

Mutations in FGFR2 and PTEN

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Herbal and Botanical

Cetuximab

Antineoplastic Agents, Immunological

Cola

cetuximab (Erbitux®) - Initial dose - Day 1 (Week 1): 400 mg/m2 IV over 120 minutes Maintenance Infusions (subsequent weeks): 250 mg/m2 IV over 60 minutes

cetuximab

brivanib alaninate

Lillian L. Siu, MD, FRCPC

RATIONALE: Brivanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving brivanib together with cetuximab is more effective than cetuximab alone in treating patients with metastatic colorectal cancer.

PURPOSE: This randomized phase III trial is studying cetuximab to see how well it works compared with cetuximab given together with brivanib in treating patients with metastatic colorectal cancer.

OBJECTIVES:

Primary

* To compare the overall survival of patients with previously treated K-Ras wild type metastatic colorectal carcinoma treated with brivanib alaninate in combination with cetuximab versus placebo in combination with cetuximab.

Secondary

* To compare the progression-free survival of these patients.
* To compare the objective response rate and duration of response in these patients.
* To compare the quality of life of these patients.
* To compare the health utilities of these patients.
* To conduct a comparative economic evaluation of these patients.
* To evaluate the safety profile of this regimen in these patients.
* To explore an association between FGF-2, BRAF mutations, amphiregulin (AREG) and epiregulin (EREG) as determined from paraffin embedded tumor specimens and the potential for clinical benefit from the addition of brivanib alaninate or placebo to cetuximab in terms of overall survival, progression-free survival and objective response rate compared to cetuximab alone.
* To explore associations with mRNA and/or protein expression and/or variations in genes associated with epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), angiogenesis, and other related pathways and the potential for clinical benefit from the addition of brivanib alaninate to cetuximab in terms of overall survival, progression-free survival, and objective response rate compared to cetuximab alone.
* To explore an association with changes of Collagen IV in the blood and the potential for clinical benefit from the addition of brivanib alaninate to cetuximab in terms of overall survival, progression-free survival and objective response rate compared to cetuximab alone.
* To establish a comprehensive tumor bank linked to a clinical database for the further study of molecular markers in colorectal cancer.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center and ECOG performance status (0-1 vs 2). Patients are randomized to 1 of 2 arms.

* Arm I: Patients receive oral brivanib alaninate once daily and cetuximab IV over 60-120 minutes once weekly.
* Arm II: Patients receive oral placebo once daily and cetuximab IV over 60-120 minutes once weekly.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Tumor tissue and blood samples are collected for correlative studies. Samples are analyzed for biomarker levels (Collagen IV, FGF-2, and epiregulin, amphiregulin, and BRAF mutation status) and correlation with response.

After completion of study treatment, patients are followed at 4 weeks and then every 8 weeks thereafter.

Cetuximab With or Without Brivanib in Treating Patients With K-Ras Wild Type Tumours and Metastatic Colorectal Cancer

A Phase III Randomized Study of Brivanib Alaninate (BMS-582664) in Combination With Cetuximab (Erbitux®) Versus Placebo in Combination With Cetuximab (Erbitux®) in Patients With K-RAS Wild Type Tumors Previously Treated With Combination Chemotherapy for Metastatic Colorectal Carcinoma

NCIC Clinical Trials Group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ascending Multiple-Dose Study of Brivanib Alaninate in Combination With Chemotherapeutic Agents in Subjects With Advanced Cancers	NCT00798252	Advanced Cancer	Capecitabine Doxorubicin Ixabepilone Docetaxel Paclitaxel Brivanib alanin...	18 Years - 75 Years	Bristol-Myers Squibb
Brivanib Alaninate in Treating Patients With Persistent or Recurrent Cervical Cancer	NCT01267253	Cervical Adenoc... Cervical Adenos... Cervical Squamo... Persistent Dise... Recurrent Cervi...	Brivanib Alanin... Laboratory Biom...	18 Years -	GOG Foundation
Brivanib Alaninate in Treating Patients With Recurrent or Persistent Endometrial Cancer	NCT00888173	Endometrial Ade... Endometrial Cle... Endometrial Mix... Endometrial Muc... Endometrial Ser... Endometrial Squ... Endometrial Tra... Endometrial Und... Recurrent Uteri...	Brivanib Alanin... Laboratory Biom...	18 Years -	GOG Foundation
Cetuximab With or Without Brivanib in Treating Patients With K-Ras Wild Type Tumours and Metastatic Colorectal Cancer	NCT00640471	Colorectal Canc...	cetuximab brivanib alanin...	18 Years -	Canadian Cancer Trials Group

Spots Global Cancer Trial Database for brivanib alaninate