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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AVEO Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01478594
First received: November 21, 2011
Last updated: June 20, 2014
Last verified: June 2014
  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:


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: January 2015
Primary Completion Date: February 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 20, 2014
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 August 28, 2014