Bevacizumab vs Dacarbazine in Metastatic Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
The Norwegian Melanoma Group
The Norwegian Cancer Association
Information provided by (Responsible Party):
Haukeland University Hospital
ClinicalTrials.gov Identifier:
NCT01705392
First received: October 8, 2012
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to compare efficacy of bevacizumab monotherapy with standard chemotherapy (DTIC) in patients with metastatic malignant melanoma. In addition, we want to evaluate the predictive value of a set biomarkers associated with vascular endothelial growth factor (VEGF) dependent angiogenesis. Also, we aim to identify mechanisms causing acquired resistance to treatment with bevacizumab and escape mechanisms caused by other angiogenic growth factors than VEGF. Finally, we want to analyze safety and influence on outcome variables by primary prevention of bevacizumab induced hypertension by low dose beta blockers in comparison with an ACE inhibitor.


Condition Intervention Phase
Metastatic Malignant Melanoma
Unresectable Malignant Melanoma
Drug: Bevacizumab
Drug: Propranolol
Drug: Enalapril
Drug: Dacarbazine
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 Randomized Phase II Trial Comparing Bevacizumab Monotherapy With Dacarbazine (DTIC) in Treatment of Malignant Melanoma, Focusing on Angiogenic Markers and Prevention of Hypertension.

Resource links provided by NLM:


Further study details as provided by Haukeland University Hospital:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: Average of 6 months ] [ Designated as safety issue: No ]
    Participants will be followed for the duration of the treatment and as long as they do not progress, an expected average of 6 months


Secondary Outcome Measures:
  • Response Rates according to RECIST [ Time Frame: Average 6 months ] [ Designated as safety issue: No ]
    Participants will be followed for the duration of the treatment with CT scans for response evaluation every 2 months for an expected average of 6 months.

  • Disease control rate at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Number of patient with complete response, partial response or stable disease at 6 months

  • Prevention of hypertension by beta blockers or ACE-inhibitors [ Time Frame: Average of 6 months ] [ Designated as safety issue: Yes ]
    Safety and influence on outcome variables by primary prevention of bevacizumab induced hypertension, by low dose beta blockers (propranolol 80 mg x 1), in comparison with an ACE inhibitor (enalapril 5 mg x 1). Patients will be monitored as during active treatment with anti hypertensive drugs and bevacizumab for an average of 6 months.

  • Overall survival [ Time Frame: Average og 12 months ] [ Designated as safety issue: No ]
    Participants will be followed until death for overall survival data, an expected average of 12 months


Estimated Enrollment: 120
Study Start Date: January 2013
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab plus propranolol
Bevacizumab 10mg/kg q2w plus propranolol 80 mg x 1
Drug: Bevacizumab
Bevacizumab 10 mg/kg q3w
Other Name: Avastin
Drug: Propranolol
Propranolol 80 mg x 1
Other Names:
  • Inderal
  • Inderal retard
Experimental: Bevacizumab plus enalapril
Bevacizumab 10mg/kg q2w plus enalapril 5 mg x 1
Drug: Bevacizumab
Bevacizumab 10 mg/kg q3w
Other Name: Avastin
Drug: Enalapril
Enalapril 5 mg x 1
Other Names:
  • Renitec
  • Vasotec
Active Comparator: Dacarbazine
Dacarbazine 1000mg/m2 q3w
Drug: Dacarbazine
dacarbazine 1000 mg/m2 q3w
Other Names:
  • Dacarbazine
  • DTIC

  Eligibility

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

Inclusion Criteria:

  • Previously treated or untreated, histologically confirmed, metastatic and unresectable melanoma with progressive disease
  • Both BRAF wild type patients as well as BRAF mutated patients are allowed. For BRAF mutated patients, BRAF targeting agents should be considered in first line if otherwise indicated and no contraindications exist.
  • WHO performance status 0-1
  • Age >18 years,
  • Known BRAF mutation
  • Able to undergo outpatient treatment
  • Patients must have clinically and/or radiographically documented measurable disease according to RECIST.
  • All radiology studies must be performed within 28 days prior to registration (35 days if negative).
  • At least 4 weeks since adjuvant interferon alpha
  • At least 4 weeks since 1st line treatment in case of metastasis
  • Major surgical procedure or significant traumatic injury > 28 days prior to study treatment start. Biopsy or fine needle aspiration > 2 days prior to study treatment start. Central venous line placement must be inserted at least 2 days prior to treatment start.
  • Only patients with irradiated and asymptomatic brain metastases and off dexamethasone are allowed.
  • Hematology: absolute granulocytes > 1.0 x 109/L
  • Platelets > 100 x 109/L
  • Bilirubin < 1.5 x upper normal limit
  • Serum creatinine < 1.5 x upper normal limits
  • LDH < 1.5 x upper normal limit
  • INR < 1.5
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  • Before patient registration/randomization, written informed consent must be given according to national and local regulations.

Exclusion Criteria:

  • No previous DTIC
  • No previous anti-VEGF targeted therapies
  • No pregnant or lactating patients can be included
  • No clinical evidence of coagulopathy
  • No unstable angina pectoris
  • No AV-block II or III without pacemaker
  • No severe congestive heart failure
  • No untreated phaeochromocytoma
  • No severe bradycardia
  • No severe hypotension
  • No severe impairment of peripheral arterial circulation
  • No uncontrolled cardiac arrhythmia
  • No severe asthma or COPD
  • No uncontrolled diabetes mellitus
  • No Angioneurotic edema
  • No severe Aortic valve stenosis
  • No severe hypertrophic cardiomyopathy
  • No severe renal dysfunction
  • No patients on beta blockers/ ACE inhibitors by inclusion unable/unwilling to discontinue beta blockers/ ACE inhibitors and convert to other classes of antihypertensive drugs
  • No full-dose oral coumarin-derived anticoagulants (INR>1.5) or heparin, thrombolytic agents, or chronic, daily treatment with aspirin (>325 mg/day).
  • No uncontrolled hypertension
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01705392

Locations
Norway
Haukeland University Hospital
Bergen, Norway, 5021
Sponsors and Collaborators
Haukeland University Hospital
The Norwegian Melanoma Group
The Norwegian Cancer Association
Investigators
Principal Investigator: Oddbjorn Straume, MD PhD Department of Oncology, Haukeland University Hospital, Bergen, Norway
Study Director: Olav Mella, MD PhD Department of Oncology, Haukeland University Hospital, Bergen, Norway
  More Information

No publications provided

Responsible Party: Haukeland University Hospital
ClinicalTrials.gov Identifier: NCT01705392     History of Changes
Other Study ID Numbers: 2012/910
Study First Received: October 8, 2012
Last Updated: December 3, 2013
Health Authority: Norway: Norwegian Medicines Agency

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Dacarbazine
Bevacizumab
Propranolol
Enalapril
Enalaprilat
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Cardiovascular Agents
Antihypertensive Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Vasodilator Agents
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014