Malignant MelanomaPhase 2NCT01069627
A Study of Avastin (Bevacizumab) in Combination With Fotemustine in Patients With Metastatic Melanoma
A Phase 2 study testing bevacizumab [Avastin] and fotemustine in people with Malignant Melanoma, run by Hoffmann-La Roche at 4 sites in Italy.
Trial summary
This study will investigate the efficacy and safety of bevacizumab + fotemustine in patients with stage IV melanoma, previously untreated with chemo- or immunotherapy for metastatic disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- bevacizumab [Avastin] and fotemustine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 4 sitesItaly
- Study dates
- Dec 2006to Jul 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- cutaneous malignant melanoma;
- advanced, inoperable stage IV melanoma;
- measurable and/or evaluable sites of metastases.
Who cannot join
- prior chemotherapy and/or IFN/IL2 based immunotherapy for metastatic disease;
- prior malignancies within past 5 years, with the exception of cured non-melanoma skin cancer, or in situ cancer of cervix;
- clinically significant cardiovascular disease;
- ongoing treatment with aspirin (>325mg/day) or other medications known to predispose to gastrointestinal ulceration.
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
Study site
Florence, 50100
Study site
Genova, 16132
Study site
Milan, 20133
Study site
Torino, 10126
About this study
Official title: An Open-label Study to Assess the Anti-tumor Activity of Avastin in Combination With Fotemustine as First-line Therapy in Patients With Metastatic Melanoma
This study will investigate the efficacy and safety of bevacizumab + fotemustine in patients with stage IV melanoma, previously untreated with chemo- or immunotherapy for metastatic disease. Patients will receive Avastin (15mg/kg intravenously[IV]) on Day 1 of every 3 week cycle, in combination with fotemustine (100mg/m² IV) on Days 1, 8 and 15, followed by 4 weeks rest, followed by 100mg/m² IV every 3 weeks for 4-6 cycles. The anticipated time on study treatment is until disease progression, and the target sample size is <100 individuals.
- Conditions
- Malignant Melanoma
- Being tested
- bevacizumab [Avastin], fotemustine
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumab [Avastin]Drug
15 mg/kg intravenously on day 1 of every 3 week cycle
fotemustineDrug
100 mg/m² intravenously on Days 1, 8, and 15, followed by 4 weeks of rest, then every 21 days up to 4 to 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: bevacizumab [Avastin]; Drug: fotemustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Complete Response (CR) or Partial Response (PR)
The percentage of participants with an objective response, defined as achieving CR or PR, as evaluated by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target), PR: at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Percentage of Participants With Clinical Benefit of CR, PR, or Stable Disease (SD)
The percentage of participants with an objective response of CR, PR, or SD, as evaluated by RECIST criteria. CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target), PR: at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for pregressive disease (PD). The clinical benefit was finally assessed by computing absolute frequencies and percentages participants with best overall tumor response equal to CR, PR, or SD.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Secondary outcomes (16)
Time to Progression (TTP) - Percentage of Participants With an Event
TTP was defined as the time in days from the date of first study treatment until the date of tumor progression or death. Failure events were defined as occurrence of death or progression of disease. Data for participants who were alive without tumor progression at the end of the study were censured at the end of the observation period.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
TTP - Time to Event
TTP was defined as the time in days from the of first study treatment until the date of tumor progression or death. Failure events were defined as occurrence of death or progression of disease. Data for participants who were alive without tumor progression at the end of the study were censored at the end of the observation period. Median TTP was estimated using the Kaplan-Meier method.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Duration of CR - Percentage of Participants With an Event
Evaluated only for participants whose best overall response was CR. The start date was the date of first documented CR and the end date was defined as the date of first documented progression of disease, or death. Participants who did not experience progression of disease were censored at last tumor assessment date or at maximum follow-up.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Duration of CR - Time to Event
The start date was the date of first documented CR and the end date was defined as the date of first documented progression of disease, or death. Participants who did not experience progression of disease were censored at last tumor assessment date or at maximum follow-up. Median duration of CR was estimated using the Kaplan-Meier method.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Duration of Overall Response of CR or PR - Percentage of Participants With an Event
The start date was the date of first documented CR or PR and the end date was defined as the date of first documented progression of disease, or death. Participants who did not experience progression of disease were censored at last tumor assessment date or at maximum follow-up.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Duration of Overall Response of CR or PR - Time to Event
The start date was the date of first documented CR or PR and the end date was defined as the date of first documented progression of disease. Participants who did not experience progression of disease were censored at last tumor assessment date or at maximum follow-up. Median duration of CR or PR was estimated using the Kaplan-Meier method.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Duration of Stable Disease - Percentage of Participants With an Event
Stable disease was defined as achieving CR, PR, or SD. The start date was the date of first documented CR, PR, or SD and the end date was defined as the date of first documented progression of disease, or death. Participants who did not experience progression of disease were censored at last tumor assessment date or at maximum follow-up.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Duration of Stable Disease - Time to Event
Stable disease was defined as achieving CR, PR, or SD. The start date was the date of first documented CR, PR, or SD and the end date was defined as the date of first documented progression of disease, or death. Participants who did not experience progression of disease were censored at last tumor assessment date or at maximum follow-up. Median duration of CR, PR, or SD was estimated using the Kaplan-Meier method.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Overall Survival (OS) - Percentage of Participants With an Event
OS was defined as the time from the starting day of the therapy up to death or the last date the participant was known to be alive.
Measured: Baseline, every 3 weeks to end-of-treatment, every 3 months during follow-up, to death or end-of-study (maximum of 36 months)
OS - Time to Event
The time from the starting day of the therapy up to death or the last date the participant was known to be alive. Median OS was estimated using the Kaplan-Meier method.
Measured: Baseline, every 3 weeks to end-of-treatment, every 3 months during follow-up, to death or end-of-study (maximum of 36 months)
Time to Treatment Failure (TTF) - Percentage of Participants With an Event
The time from date of start of treatment to the earliest among date of progression, date of death due to any cause, or date of discontinuation due to reason other than 'Protocol Violation' or 'Administrative Problem'. For the participants who did not experience treatment failure, TTF was censored at last adequate tumour assessment.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
TTF - Time to Event
The time from date of start of treatment to the earliest among date of progression, date of death due to any cause, or date of discontinuation due to reason other than 'Protocol Violation' or 'Administrative Problem'. For the participants who did not experience treatment failure, TTF was censored at last adequate tumour assessment. Median TTF was estimated using the Kaplan-Meier method.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Time to CR - Percentage of Participants With an Event
The time between date of start of treatment until first documented CR. This analysis included all responders. Participants who did not achieve a confirmed CR were censored at last adequate tumour assessment date or at maximum follow-up.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Time to CR - Time To Event
The time between date of start of treatment until first documented CR. This analysis included all responders. Participants who did not achieve a confirmed CR were censored at last adequate tumour assessment date or at maximum follow-up. Mean time to CR was estimated using the Kaplan-Meier method.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Time to Overall Response of CR or PR - Percentage of Participants With an Event
The time between date of start of treatment until first documented response of CR or PR. This analysis included all responders. Participants who did not achieve a confirmed CR or PR were censored at last adequate tumour assessment date or at maximum follow-up.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Time to Overall Response of CR or PR - Time to Event
The time between date of start of treatment until first documented response of CR or PR. This analysis included all responders. Participants who did not achieve a confirmed CR or PR were censored at last adequate tumor assessment date or at maximum follow-up. Mean time to CR or PR was estimated using the Kaplan-Meier method.
Measured: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2010 (estimated)
- Study startDec 2006
- Primary completionJul 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study chair, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01069627
- Sponsor's protocol ID
- ML19309
- Status last verified
- Nov 2018
- First submitted
- 15 Dec 2009
- Last updated
- 6 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Del Vecchio M, Mortarini R, Canova S, Di Guardo L, Pimpinelli N, Sertoli MR, Bedognetti D, Queirolo P, Morosini P, Perrone T, Bajetta E, Anichini A. Bevacizumab plus fotemustine as first-line treatment in metastatic melanoma patients: clinical activity and modulation of angiogenesis and lymphangiogenesis factors. Clin Cancer Res. 2010 Dec 1;16(23):5862-72. doi: 10.1158/1078-0432.CCR-10-2363. Epub 2010 Oct 28.
PubMed 21030496
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study to Assess the Anti-tumor Activity of Avastin in Combination With Fotemustine as First-line Therapy in Patients With Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT01069627
- Acronym / sponsor ID
- ML19309
- Conditions
- Malignant Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Dec 2006 (actual)
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 17 Feb 2010 (estimated)
- Results
- Posted 25 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate the efficacy and safety of bevacizumab + fotemustine in patients with stage IV melanoma, previously untreated with chemo- or immunotherapy for metastatic disease. Patients will receive Avastin (15mg/kg intravenously[IV]) on Day 1 of every 3 week cycle, in combination with fotemustine (100mg/m² IV) on Days 1, 8 and 15, followed by 4 weeks rest, followed by 100mg/m² IV every 3 weeks for 4-6 cycles. The anticipated time on study treatment is until disease progression, and the target sample size is <100 individuals.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: bevacizumab [Avastin], Drug: fotemustine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- cutaneous malignant melanoma;
- advanced, inoperable stage IV melanoma;
- measurable and/or evaluable sites of metastases.
Key exclusion criteria (4 listed)
- prior chemotherapy and/or IFN/IL2 based immunotherapy for metastatic disease;
- prior malignancies within past 5 years, with the exception of cured non-melanoma skin cancer, or in situ cancer of cervix;
- clinically significant cardiovascular disease;
- ongoing treatment with aspirin (>325mg/day) or other medications known to predispose to gastrointestinal ulceration.
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 |
|---|---|---|
| bevacizumab [Avastin]15 mg/kg intravenously on day 1 of every 3 week cycle | Drug | 1 |
| fotemustine100 mg/m² intravenously on Days 1, 8, and 15, followed by 4 weeks of rest, then every 21 days up to 4 to 6 cycles | Drug | 1 |
Primary outcome
Percentage of Participants With Complete Response (CR) or Partial Response (PR)
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
The percentage of participants with an objective response, defined as achieving CR or PR, as evaluated by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target), PR: at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Percentage of Participants With Clinical Benefit of CR, PR, or Stable Disease (SD)
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
The percentage of participants with an objective response of CR, PR, or SD, as evaluated by RECIST criteria. CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target), PR: at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for pregressive disease (PD). The clinical benefit was finally assessed by computing absolute frequencies and percentages participants with best overall tumor response equal to CR, PR, or SD.
16 secondary outcomes
Time to Progression (TTP) - Percentage of Participants With an Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
TTP - Time to Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Duration of CR - Percentage of Participants With an Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Duration of CR - Time to Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Duration of Overall Response of CR or PR - Percentage of Participants With an Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Duration of Overall Response of CR or PR - Time to Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Duration of Stable Disease - Percentage of Participants With an Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Duration of Stable Disease - Time to Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Overall Survival (OS) - Percentage of Participants With an Event
Time frame: Baseline, every 3 weeks to end-of-treatment, every 3 months during follow-up, to death or end-of-study (maximum of 36 months)
OS - Time to Event
Time frame: Baseline, every 3 weeks to end-of-treatment, every 3 months during follow-up, to death or end-of-study (maximum of 36 months)
Time to Treatment Failure (TTF) - Percentage of Participants With an Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
TTF - Time to Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Time to CR - Percentage of Participants With an Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Time to CR - Time To Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Time to Overall Response of CR or PR - Percentage of Participants With an Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Time to Overall Response of CR or PR - Time to Event
Time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21030496Del Vecchio M, Mortarini R, Canova S, Di Guardo L, Pimpinelli N, Sertoli MR, Bedognetti D, Queirolo P, Morosini P, Perrone T, Bajetta E, Anichini A. Bevacizumab plus fotemustine as first-line treatment in metastatic melanoma patients: clinical activity and modulation of angiogenesis and lymphangiogenesis factors. Clin Cancer Res. 2010 Dec 1;16(23):5862-72. doi: 10.1158/1078-0432.CCR-10-2363. Epub 2010 Oct 28.
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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.
Clinical Trials study chair
Hoffmann-La Roche
4 sites 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 [Avastin] and fotemustine in people with Malignant Melanoma, run by Hoffmann-La Roche at 4 sites in Italy.
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 3 inclusion and 4 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: finished, as of the sponsor's last update on 6 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. 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?
Yes. Results are posted in the registry (first posted 25 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (time frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01069627, which also lists 1 linked publication.
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 6 Dec 2018.