Bevacizumab vs Dacarbazine in Metastatic Melanoma

Metastatic Malignant Melanoma Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01705392
• Other study ID #: 2012/910
• Status: Terminated
• Phase: Phase 2
• First received: October 8, 2012
• Last updated: February 23, 2017
• Start date: January 2013
• Est. completion date: February 20, 2017

Study information

• Verified date: February 2017
• Source: Haukeland University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: February 20, 2017
• Est. primary completion date: February 20, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Melanoma
• Metastatic Malignant Melanoma
• Unresectable Malignant Melanoma

Intervention

Drug:
• Bevacizumab
Bevacizumab 10 mg/kg q3w
• Propranolol
Propranolol 80 mg x 1
• Enalapril
Enalapril 5 mg x 1
• Dacarbazine
dacarbazine 1000 mg/m2 q3w

Locations

Country	Name	City	State
Norway	Haukeland University Hospital	Bergen

Sponsors (3)

Lead Sponsor	Collaborator
Haukeland University Hospital	Norwegian Cancer Society, The Norwegian Melanoma Group

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Response Rates according to RECIST	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.	Average 6 months
Secondary	Disease control rate at 6 months	Number of patient with complete response, partial response or stable disease at 6 months	6 months
Secondary	Prevention of hypertension by beta blockers or ACE-inhibitors	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.	Average of 6 months
Secondary	Overall survival	Participants will be followed until death for overall survival data, an expected average of 12 months	Average og 12 months