A Study Combining mFOLFOX6 With Tivozanib or Bevacizumab in Patients With Metastatic Colorectal Cancer as First Line Therapy - Full Text View

Purpose

The objective of this study is to compare the progression free survival (PFS), overall survival (OS), objective response rate (ORR), time to treatment failure (TTF), duration of response (DoR), quality of life, safety and tolerability of tivozanib in combination with mFOLFOX6 and bevacizumab in combination with mFOLFOX6.

Condition	Intervention	Phase
Colorectal Cancer	Drug: Tivozanib Drug: Bevacizumab Drug: mFOLFOX6	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 2, Open Label, Multicenter, Randomized Trial Comparing Tivozanib in Combination With mFOLFOX6 to Bevacizumab in Combination With mFOLFOX6, In Stage IV Metastatic Colorectal Cancer (mCRC) Subjects

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Bevacizumab

U.S. FDA Resources

Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:

Progression-Free Survival (PFS) based on investigator radiological tumor assessment [ Time Frame: 3 years ] [ Designated as safety issue: No ]
The time from the date of randomization until objective tumor progression or death due to any cause. Objective tumor progression is defined by radiological assessments by the investigators.

Secondary Outcome Measures:

Progression-Free Survival (PFS) based on Independent Radiological Review (IRR) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
The time from the date of randomization until the date of radiological disease progression assessed by the IRR or until death due to any cause, even in the absence of radiological progression.
Overall survival (OS) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
The time from the date of randomization until death from any cause.
Objective Response Rate (ORR) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
The proportion of subjects with a confirmed complete response (CR ) or partial response (PR).
Duration of Response (DoR) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
The time from the date of the first documented radiological response (CR or PR) to the date of first documented radiological progression.
Time to Treatment Failure (TTF) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
The time from randomization to treatment discontinuation for any reason, including disease progression, toxicity, withdrawn consent, or death.
Health Related Quality of life (HRQoL) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Time to deterioration in HRQoL measured by Colorectal cancer (CRC) subscale of the Functional Assessment of cancer Therapy Colorectal (FACT-C) scale, change in score from baseline using the EQ-5D and Fact Colorectal Symptom Index (FCSI).
Safety as assessed by physical examination, vital signs, laboratory assessments, 12-lead electrocardiogram (ECGs), and adverse events [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Assessment of relationship of biomarker that may be predictive of level of response between 2 study arms: Biomarker Lactate Dehydrogenase ( LDH) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Assessment of relationship of biomarker that may be predictive of level of response between 2 study arms: Vascular Endothelial Growth Factor (VEGF-C,VEGF-D, VEGF-A) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Assessment of relationship of biomarker that may be predictive of relationship between 2 study arms: CD68 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Assessment of relationship of biomarker that may be predictive of level of response between 2 study arms: myeloid-derived gene signature (MGS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Assessment of relationship of biomarker that may be predictive of level of response between 2 study arms: Serum soluble cytokines [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment:	265
Study Start Date:	November 2011
Estimated Study Completion Date:	December 2015
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm A: Tivozanib + mFOLFOX6	Drug: Tivozanib Oral and Intravenous Other Names: AV951 ASP4130 Drug: mFOLFOX6 Oxaliplatin, Leucovorin Calcium, Fluorouracil Bolus, Fluorouracil Infusion
Active Comparator: Arm B: Bevacizumab + mFOLFOX6	Drug: Bevacizumab Intravenous Other Name: Avastin Drug: mFOLFOX6 Oxaliplatin, Leucovorin Calcium, Fluorouracil Bolus, Fluorouracil Infusion

Detailed Description:

A 2:1 randomization between tivozanib in combination with mFOLFOX6 to bevacizumab in combination with mFOLFOX6. Subjects will be stratified by origin of cancer, Lactate Dehydrogenase (LDH) status, and number of metastatic sites.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Documented diagnosis of metastatic colorectal cancer
One measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
No prior systemic chemotherapy for advanced colorectal cancer; no fluorouracil containing adjuvant therapy in previous 6 months
Eastern Cooperative Oncology Group (ECOG) status of 0 or 1

Exclusion Criteria:

Any prior Vascular Endothelial Growth Factor (VEGF)-directed therapy or any other agent or investigational agent targeting the VEGF pathway
Primary Central Nervous System (CNS) malignancies or CNS metastases
Hematologic abnormalities:
- Hemoglobin < 9.0 g/dL,
- ANC < 2000 per mm3,
- Platelet count < 100,000 per mm3,
- Prothrombin (PT) or Partial Thromboplastin Time (PTT) > 1.5 X Upper Limit of Normal (ULN)
Serum chemistry abnormalities:
- Total bilirubin > 1.5 X ULN,
- Aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) > 2.5 X ULN,
- Alkaline phosphatase > 2.5 X ULN,
- Serum albumin < 2.0 g/dL,
- Creatinine > 1.5 X ULN,
- Proteinuria > 2+ by urine dipstick
Significant cardiovascular disease
Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug
Non-healing wound, bone fracture, or skin ulcer
Inadequate recovery from any prior surgical procedure or major surgical procedure within 8 weeks prior to administration, or anticipation of major surgical procedure during the course of the study
History of significant gastrointestinal (GI) toxicity, diarrhea, or stomatitis within the last 6 weeks
An active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug
Serious/active infection or infection requiring antibiotics
Significant bleeding disorders within 6 months prior to administration of first dose of study drug
Active second primary malignancy, other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer and ductal or lobular carcinoma in situ of the breast. Subject is not considered to have a currently active malignancy if they have completed anti-cancer therapy and have been disease free for > 5 years
History of allergic reactions, or intolerance, attributed to compounds of similar chemical or biologic composition to 5-fluorouracil, history of Grade 3 hypersensitivity to oxaliplatin, history of allergic reaction to folic acid
Female subject is pregnant or lactating
Known history of genetic or acquired immune suppression disease including Human Immunodeficiency Virus (HIV); subjects on immune suppressive therapy for organ transplant
Inability to swallow pills, malabsorption syndrome or gastrointestinal disease, major resection of the stomach or small bowel, or gastric bypass
Uncontrolled neuro-psychiatric disorder or altered mental status
Peripheral neuropathy ≥ Grade 2
Participating in another interventional protocol

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01478594

Show 73 Study Locations

Sponsors and Collaborators

Astellas Pharma Inc

AVEO Pharmaceuticals, Inc.

Investigators

Study Director:

Medical Director

Astellas Pharma Global Development

More Information

No publications provided

Responsible Party:	Astellas Pharma Inc
ClinicalTrials.gov Identifier:	NCT01478594 History of Changes
Other Study ID Numbers:	4130-CL-0201, 2011-003502-24
Study First Received:	November 21, 2011
Last Updated:	June 17, 2013
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Belgium: Federal Agency for Medicinal Products and Health Products United Kingdom: Medicines and Healthcare Products Regulatory Agency Czech Republic: State Institute for Drug Control Australia: Department of Health and Ageing Therapeutic Goods Administration Italy: The Italian Medicines Agency Spain: Ministry of Health and Consumption Austria: Agency for Health and Food Safety Finland: Finnish Medicines Agency Hungary: National Institute of Pharmacy Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Astellas Pharma Inc:

metastatic colorectal cancer
Avastin
bevacizumab
tivozanib

mFOLFOX6
BATON-CRC
AV951
ASP4130

Additional relevant MeSH terms:

Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases

Rectal Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013