Pancreatic NeoplasmPhase 3VANILLANCT00574275
Aflibercept Compared to Placebo in Term of Efficacy in Patients Treated With Gemcitabine for Metastatic Pancreatic Cancer
A Phase 3 study testing Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) and Gemcitabine in people with Pancreatic Neoplasm, run by Sanofi at 24 sites in 24 countries.
Trial summary
The main objective of the study was to evaluate the effectiveness of aflibercept treatment by comparison to placebo in increasing the overall survival (OS) in participants with metastatic pancreatic cancer, treated with gemcitabine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Neoplasm
- What is being tested?
- Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) and Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 546 participants
- Where
- 24 sitesin 24 countries
- Study dates
- Dec 2007to Nov 2010
- Phase
- Phase 3
- 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
- Cytologically or histologically confirmed evidence of epithelial cancer (adenocarcinoma) of the exocrine pancreas
- Metastatic disease
- No prior chemotherapy for pancreatic disease
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- Adequate renal, liver and bone marrow functions
Who cannot join
- Less than 42 days elapsed from prior major surgery (28 days from other prior surgery) to the time of randomization
- Prior treatment with anti-VEGF or VEGF-Receptor-inhibitors
- Uncontrolled hypertension
- Pregnancy or breastfeeding
- Participant with reproductive potential (M/F) without effective method of contraception
- The above information is not intended to contain all considerations relevant to potential participation in a clinical trial.
Trial locations and contacts
24 sites in 24 countries.
24 sites in 24 countries
United States1 site
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, 08807
About this study
Official title: A Multinational, Randomized, Double-blind Study, Comparing the Efficacy of Aflibercept Once Every 2 Weeks Versus Placebo in Patients Treated With Gemcitabine for Metastatic Pancreatic Cancer
The main objective of the study was to evaluate the effectiveness of aflibercept treatment by comparison to placebo in increasing the overall survival (OS) in participants with metastatic pancreatic cancer, treated with gemcitabine.
The secondary objectives were to evaluate progression free survival, clinical benefit, overall response, safety and immunogenicity of aflibercept, in the two treatment arms (Arm 1: Aflibercept and Gemcitabine; Arm 2: Placebo and Gemcitabine).
The study included an interim analysis of OS. In accordance with the study protocol, an interim analysis was performed for the purpose of futility and overwhelming efficacy. On the basis of the interim analysis, the Data Monitoring Committee (DMC) recommended that this study be terminated for futility based on predefined boundary rules.
Read the detailed description
The study included:
- A screening visit of up to 21 days prior to randomization
- Randomization at baseline
- A Treatment period (initiated within 3 days of randomization), which included 28-day treatment cycles in both arms until predefined treatment discontinuation criteria were met
- A follow-up visit 30 days after discontinuation of treatment,
- A post study treatment follow-up period until death or the study cutoff date.
The criteria for treatment discontinuation were:
- Participant (or legal representative) chose to withdraw from treatment
- The investigator thought that continuation of the study would be detrimental to the participants well-being, such as:
- Disease progression
- Unacceptable AEs not manageable by symptomatic therapy, dose delay, or dose modification
- Intercurrent illness that prevented further administration of study treatment
- Noncompliance with the study protocol
- Participant was lost to follow-up
- Unblinding of the participant's investigational treatment
- Conditions
- Pancreatic Neoplasm
- Being tested
- Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®), Placebo, Gemcitabine
- Keywords
- metastatic pancreatic cancer, angiogenesis inhibitor, gemcitabine
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)Drug
4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle.
PlaceboDrug
4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle
GemcitabineDrug
Also called Gemzar
1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.
| Study group | Role | What they receive |
|---|---|---|
| Placebo and Gemcitabine | Placebo comparator | Participants with metastatic pancreatic cancer administered Placebo and 1000 mg/m^2 Gemcitabine. Receives: Drug: Placebo; Drug: Gemcitabine |
| Aflibercept and Gemcitabine | Experimental | Participants with metastatic pancreatic cancer administered 4 mg/kg Aflibercept and 1000 mg/m^2 Gemcitabine. Receives: Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®); Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
OS is the time interval from the date of randomization to the date of death due to any cause. If death was not observed during the study, data on OS were censored at the earlier of the last date participant was known to be alive, or the study data cutoff date (11 September 2009).
OS time was estimated from Kaplan-Meier Plots.
Measured: From the first randomization until the end of study data cutoff date (approximately 2 years)
Secondary outcomes (5)
Progression Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors [RECIST] Criteria
PFS was the time interval from the date of registration to the date of progression, or death from any cause if it occurs before tumor progression is documented. Tumor progression was assessed using RECIST criteria, by which progression was a pre-defined increase in the size of existing tumors or appearance of one or more new tumors.
If a participant did not progress or die, the progression was censored to the date of the last valid tumor assessment or data cut-off, whichever was earlier.
Median PFS time was estimated from Kaplan-Meier Plots.
Measured: From the first randomization until the end of study data cutoff date (approximately 2 years)
Objective Response Rate (ORR) Assessed by the Investigators According to RECIST Criteria
Objective response (OR) included complete response [CR] and partial response [PR]. OR was to be assessed by the Investigators according to RECIST criteria, and confirmed by repeating tumor imaging at least 4 weeks after the first radiological documentation of response.
CR would reflect the disappearance of all tumor lesions and PR would reflect a defined reduction of tumor burden.
However, OR analysis was not performed, as the study was terminated due to futility.
Measured: From the first randomization until the end of the study data cutoff date (approximately 2 years)
Clinical Benefit
Clinical benefit was to be assessed in all participants by time to symptom worsening (TTSW), evaluated from the time of randomization to symptom worsening, as well as by improvement in tumor related symptoms.
However, this analysis was not performed, as the study was terminated due to futility.
Measured: From the first randomization until the end of the study data cutoff date (approximately 2 years)
Safety-Number of Participants With Adverse Events (AE)
All AEs regardless of seriousness or relationship to study treatment, spanning from the signature of informed consent until 30 days after the last administration of study treatment, were recorded. The number of participants with all treatment emergent adverse events (TEAE), serious adverse events (SAE), TEAE leading to death, and TEAE leading to permanent treatment discontinuation are reported.
Measured: up to 30 days after treatment discontinuation. SAEs and related AEs were followed till resolved or stabilized.
Number of Participants With Anti-drug Antibodies
Anti-drug antibodies in the participants blood sample were detected using a validated immunoassay. The validated lower limit of detection (LLOD) for the assay was about 5.4 ng/mL in the absence of aflibercept and about 25.2 ng/mL in the presence of 20 μg/mL of aflibercept.
Measured: Up to 90 days post last dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2007 (estimated)
- Study startDec 2007
- Primary completionOct 2009
- Study completionNov 2010
Why it stopped: Data Monitoring Committee concluded after a planned interim analysis that aflibercept added to gemcitabine would be unable to demonstrate improved survival
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 Pancreatic NeoplasmStudies of the same condition, open and under way.
- More trials run by SanofiThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 546 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00574275
- Sponsor's protocol ID
- EFC10547
- Other IDs
- EudraCT 2007-003476-19
- Acronym
- VANILLA
- Status last verified
- May 2016
- First submitted
- 14 Dec 2007
- Last updated
- 7 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Rougier P, Riess H, Manges R, Karasek P, Humblet Y, Barone C, Santoro A, Assadourian S, Hatteville L, Philip PA. Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. Eur J Cancer. 2013 Aug;49(12):2633-42. doi: 10.1016/j.ejca.2013.04.002. Epub 2013 Apr 30.
PubMed 23642329
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multinational, Randomized, Double-blind Study, Comparing the Efficacy of Aflibercept Once Every 2 Weeks Versus Placebo in Patients Treated With Gemcitabine for Metastatic Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT00574275
- Acronym / sponsor ID
- VANILLA / EFC10547
- Conditions
- Pancreatic Neoplasm
- Keywords
- metastatic pancreatic cancer, angiogenesis inhibitor, gemcitabine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Data Monitoring Committee concluded after a planned interim analysis that aflibercept added to gemcitabine would be unable to demonstrate improved survival
- Enrolment
- 546 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- Dec 2007
- Primary completion
- Oct 2009 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 17 Dec 2007 (estimated)
- Results
- Posted 25 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objective of the study was to evaluate the effectiveness of aflibercept treatment by comparison to placebo in increasing the overall survival (OS) in participants with metastatic pancreatic cancer, treated with gemcitabine.
The secondary objectives were to evaluate progression free survival, clinical benefit, overall response, safety and immunogenicity of aflibercept, in the two treatment arms (Arm 1: Aflibercept and Gemcitabine; Arm 2: Placebo and Gemcitabine).
The study included an interim analysis of OS. In accordance with the study protocol, an interim analysis was performed for the purpose of futility and overwhelming efficacy. On the basis of the interim analysis, the Data Monitoring Committee (DMC) recommended that this study be terminated for futility based on predefined boundary rules.
Detailed description
The study included:
- A screening visit of up to 21 days prior to randomization
- Randomization at baseline
- A Treatment period (initiated within 3 days of randomization), which included 28-day treatment cycles in both arms until predefined treatment discontinuation criteria were met
- A follow-up visit 30 days after discontinuation of treatment,
- A post study treatment follow-up period until death or the study cutoff date.
The criteria for treatment discontinuation were:
- Participant (or legal representative) chose to withdraw from treatment
- The investigator thought that continuation of the study would be detrimental to the participants well-being, such as:
- Disease progression
- Unacceptable AEs not manageable by symptomatic therapy, dose delay, or dose modification
- Intercurrent illness that prevented further administration of study treatment
- Noncompliance with the study protocol
- Participant was lost to follow-up
- Unblinding of the participant's investigational treatment
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo and Gemcitabine | Placebo comparator | Drug: Placebo, Drug: GemcitabineParticipants with metastatic pancreatic cancer administered Placebo and 1000 mg/m^2 Gemcitabine. |
| Aflibercept and Gemcitabine | Experimental | Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®), Drug: GemcitabineParticipants with metastatic pancreatic cancer administered 4 mg/kg Aflibercept and 1000 mg/m^2 Gemcitabine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Cytologically or histologically confirmed evidence of epithelial cancer (adenocarcinoma) of the exocrine pancreas
- Metastatic disease
- No prior chemotherapy for pancreatic disease
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- Adequate renal, liver and bone marrow functions
Key exclusion criteria (6 listed)
- Less than 42 days elapsed from prior major surgery (28 days from other prior surgery) to the time of randomization
- Prior treatment with anti-VEGF or VEGF-Receptor-inhibitors
- Uncontrolled hypertension
- Pregnancy or breastfeeding
- Participant with reproductive potential (M/F) without effective method of contraception
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 |
|---|---|---|
| Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. | Drug | Aflibercept and Gemcitabine |
| Placebo4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle | Drug | Placebo and Gemcitabine |
| GemcitabineAlso: Gemzar1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles. | Drug | Aflibercept and Gemcitabine, Placebo and Gemcitabine |
Primary outcome
Overall Survival (OS)
Time frame: From the first randomization until the end of study data cutoff date (approximately 2 years)
OS is the time interval from the date of randomization to the date of death due to any cause. If death was not observed during the study, data on OS were censored at the earlier of the last date participant was known to be alive, or the study data cutoff date (11 September 2009). OS time was estimated from Kaplan-Meier Plots.
5 secondary outcomes
Progression Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors [RECIST] Criteria
Time frame: From the first randomization until the end of study data cutoff date (approximately 2 years)
Objective Response Rate (ORR) Assessed by the Investigators According to RECIST Criteria
Time frame: From the first randomization until the end of the study data cutoff date (approximately 2 years)
Clinical Benefit
Time frame: From the first randomization until the end of the study data cutoff date (approximately 2 years)
Safety-Number of Participants With Adverse Events (AE)
Time frame: up to 30 days after treatment discontinuation. SAEs and related AEs were followed till resolved or stabilized.
Number of Participants With Anti-drug Antibodies
Time frame: Up to 90 days post last dose of study drug
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23642329Rougier P, Riess H, Manges R, Karasek P, Humblet Y, Barone C, Santoro A, Assadourian S, Hatteville L, Philip PA. Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. Eur J Cancer. 2013 Aug;49(12):2633-42. doi: 10.1016/j.ejca.2013.04.002. Epub 2013 Apr 30.
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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 Sciences & Operations study director
Sanofi
24 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) and Gemcitabine in people with Pancreatic Neoplasm, run by Sanofi at 24 sites in 24 countries.
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 5 inclusion and 6 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 7 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Argentina, Austria, Belgium, Bulgaria and 19 more countries. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Sep 2012). 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?
Overall Survival (OS) (time frame: From the first randomization until the end of study data cutoff date (approximately 2 years)). 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 NCT00574275, 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 7 Jun 2016.