Metastatic Malignant MelanomaPhase 2NCT01705392
Bevacizumab vs Dacarbazine in Metastatic Melanoma
A Phase 2 study testing Bevacizumab, Propranolol and Enalapril in people with Metastatic Malignant Melanoma and Unresectable Malignant Melanoma, run by Haukeland University Hospital at 1 site in Norway.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Malignant Melanoma, Unresectable Malignant Melanoma
- What is being tested?
- Bevacizumab, Propranolol and Enalapril
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteNorway
- Study dates
- Jan 2013to 20 Feb 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 20Show fewer
- 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.
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
- Being tested
- Bevacizumab, Propranolol, Enalapril, Dacarbazine
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
Bevacizumab 10 mg/kg q3w
PropranololDrug
Also called Inderal, Inderal retard
Propranolol 80 mg x 1
EnalaprilDrug
Also called Renitec, Vasotec
Enalapril 5 mg x 1
DacarbazineDrug
Also called DTIC
dacarbazine 1000 mg/m2 q3w
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab plus propranolol | Experimental | Bevacizumab 10mg/kg q2w plus propranolol 80 mg x 1 Receives: Drug: Bevacizumab; Drug: Propranolol |
| Bevacizumab plus enalapril | Experimental | Bevacizumab 10mg/kg q2w plus enalapril 5 mg x 1 Receives: Drug: Bevacizumab; Drug: Enalapril |
| Dacarbazine | Active comparator | Dacarbazine 1000mg/m2 q3w Receives: Drug: Dacarbazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Average of 6 months
Secondary outcomes (4)
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.
Measured: Average 6 months
Disease control rate at 6 months
Number of patient with complete response, partial response or stable disease at 6 months
Measured: 6 months
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.
Measured: Average of 6 months
Overall survival
Participants will be followed until death for overall survival data, an expected average of 12 months
Measured: Average og 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2012 (estimated)
- Study startJan 2013
- Primary completion20 Feb 2017
- Study completion20 Feb 2017
Why it stopped: Lack of financing of the study drug. Not sufficient financial support.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Malignant MelanomaStudies of the same condition, open and under way.
- More trials run by Haukeland University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The Norwegian Melanoma Group, Norwegian Cancer Society
- Responsible party
- Sponsor
- Investigators
- Oddbjorn Straume, MD PhD, Principal investigator, Department of Oncology, Haukeland University Hospital, Bergen, NorwayOlav Mella, MD PhD, Study director, Department of Oncology, Haukeland University Hospital, Bergen, Norway
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01705392
- Sponsor's protocol ID
- 2012/910
- Status last verified
- Feb 2017
- First submitted
- 8 Oct 2012
- Last updated
- 24 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01705392
- Acronym / sponsor ID
- 2012/910
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of financing of the study drug. Not sufficient financial support.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Collaborators
- The Norwegian Melanoma Group, Norwegian Cancer Society
- Study start
- Jan 2013 (actual)
- Primary completion
- 20 Feb 2017 (actual)
- Study completion
- 20 Feb 2017 (actual)
- First posted
- 12 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab plus propranolol | Experimental | Drug: Bevacizumab, Drug: PropranololBevacizumab 10mg/kg q2w plus propranolol 80 mg x 1 |
| Bevacizumab plus enalapril | Experimental | Drug: Bevacizumab, Drug: EnalaprilBevacizumab 10mg/kg q2w plus enalapril 5 mg x 1 |
| Dacarbazine | Active comparator | Drug: DacarbazineDacarbazine 1000mg/m2 q3w |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: AvastinBevacizumab 10 mg/kg q3w | Drug | Bevacizumab plus enalapril, Bevacizumab plus propranolol |
| PropranololAlso: Inderal, Inderal retardPropranolol 80 mg x 1 | Drug | Bevacizumab plus propranolol |
| EnalaprilAlso: Renitec, VasotecEnalapril 5 mg x 1 | Drug | Bevacizumab plus enalapril |
| DacarbazineAlso: DTICdacarbazine 1000 mg/m2 q3w | Drug | Dacarbazine |
Primary outcome
Progression free survival
Time frame: Average of 6 months
Participants will be followed for the duration of the treatment and as long as they do not progress, an expected average of 6 months
4 secondary outcomes
Response Rates according to RECIST
Time frame: Average 6 months
Disease control rate at 6 months
Time frame: 6 months
Prevention of hypertension by beta blockers or ACE-inhibitors
Time frame: Average of 6 months
Overall survival
Time frame: Average og 12 months
Results and safety
The study was stopped early (reason given: Lack of financing of the study drug. Not sufficient financial support.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2017.
Related trials for Metastatic Malignant Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
RecruitingPhase 3
A Study With Combinations of Anti-LAG-3 and Anti-PD-1 Antibodies in Adult Participants With Advanced or Metastatic Melanoma (Harmony Head-to-Head)
Melanoma
Active, not recruitingPhase 1/2
A Study of ST-1898 for Unresectable or Metastatic Melanoma
Unresectable or Metastatic Melanoma
RecruitingPhase 2
Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
Metastatic Melanoma, Advanced Locoregional Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Oddbjorn Straume, MD PhD principal investigator
Department of Oncology, Haukeland University Hospital, Bergen, Norway
Olav Mella, MD PhD study director
Department of Oncology, Haukeland University Hospital, Bergen, Norway
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab, Propranolol and Enalapril in people with Metastatic Malignant Melanoma and Unresectable Malignant Melanoma, run by Haukeland University Hospital at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of financing of the study drug. Not sufficient financial support.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: Average of 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2017.