Bevacizumab vs Dacarbazine in Metastatic Melanoma

NCT01705392 | Terminated Phase 2 DMC

• 1 other identifier: 2012/910
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Malignant Melanoma; Unresectable Malignant Melanoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Participants will be followed for the duration of the treatment and as long as they do not progress, an expected average of 6 months

  Average of 6 months

Secondary Outcomes (4)

• Response Rates according to RECIST

  Average 6 months

• Disease control rate at 6 months

  6 months

• Prevention of hypertension by beta blockers or ACE-inhibitors

  Average of 6 months

• Overall survival

  Average og 12 months

Study Arms (3)

Bevacizumab plus propranolol

EXPERIMENTAL

Bevacizumab 10mg/kg q2w plus propranolol 80 mg x 1

Drug: Bevacizumab; Drug: Propranolol

Bevacizumab plus enalapril

EXPERIMENTAL

Bevacizumab 10mg/kg q2w plus enalapril 5 mg x 1

Drug: Bevacizumab; Drug: Enalapril

Dacarbazine

ACTIVE COMPARATOR

Dacarbazine 1000mg/m2 q3w

Drug: Dacarbazine

Interventions

Bevacizumab DRUG

Bevacizumab 10 mg/kg q3w

Also known as: Avastin

Bevacizumab plus enalapril; Bevacizumab plus propranolol

Propranolol DRUG

Propranolol 80 mg x 1

Also known as: Inderal, Inderal retard

Bevacizumab plus propranolol

Enalapril DRUG

Enalapril 5 mg x 1

Also known as: Renitec, Vasotec

Bevacizumab plus enalapril

Dacarbazine DRUG

dacarbazine 1000 mg/m2 q3w

Also known as: DTIC

Dacarbazine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Haukeland University Hospital: lead
• The Norwegian Melanoma Group: collaborator
• Norwegian Cancer Society: collaborator

Study Sites (1)

Haukeland University Hospital

Bergen, 5021, Norway

Location

MeSH Terms

Conditions

Melanoma

Interventions

Bevacizumab; Propranolol; Enalapril; Enalaprilat; Dacarbazine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Dipeptides; Oligopeptides; Peptides; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Oddbjorn Straume, MD PhD

  Department of Oncology, Haukeland University Hospital, Bergen, Norway

  PRINCIPAL INVESTIGATOR

• Olav Mella, MD PhD

  Department of Oncology, Haukeland University Hospital, Bergen, Norway

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2012
• First Posted: October 12, 2012
• Study Start: January 1, 2013
• Primary Completion: February 20, 2017
• Study Completion: February 20, 2017
• Last Updated: February 24, 2017

Record last verified: 2017-02

Locations

NO (1)