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

October 8, 2012
December 3, 2013
January 2013
June 2016   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01705392 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Bevacizumab vs Dacarbazine in Metastatic Melanoma
A Randomized Phase II Trial Comparing Bevacizumab Monotherapy With Dacarbazine (DTIC) in Treatment of Malignant Melanoma, Focusing on Angiogenic Markers and Prevention of Hypertension.

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Metastatic Malignant Melanoma
  • Unresectable Malignant Melanoma
  • Drug: Bevacizumab
    Bevacizumab 10 mg/kg q3w
    Other Name: Avastin
  • Drug: Propranolol
    Propranolol 80 mg x 1
    Other Names:
    • Inderal
    • Inderal retard
  • Drug: Enalapril
    Enalapril 5 mg x 1
    Other Names:
    • Renitec
    • Vasotec
  • Drug: Dacarbazine
    dacarbazine 1000 mg/m2 q3w
    Other Names:
    • Dacarbazine
    • DTIC
  • Experimental: Bevacizumab plus propranolol
    Bevacizumab 10mg/kg q2w plus propranolol 80 mg x 1
    Interventions:
    • Drug: Bevacizumab
    • Drug: Propranolol
  • Experimental: Bevacizumab plus enalapril
    Bevacizumab 10mg/kg q2w plus enalapril 5 mg x 1
    Interventions:
    • Drug: Bevacizumab
    • Drug: Enalapril
  • Active Comparator: Dacarbazine
    Dacarbazine 1000mg/m2 q3w
    Intervention: Drug: Dacarbazine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
120
June 2018
June 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Norway
 
NCT01705392
2012/910
Yes
Haukeland University Hospital
Haukeland University Hospital
  • The Norwegian Melanoma Group
  • The Norwegian Cancer Association
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
Haukeland University Hospital
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP