Pancreatic CancerPhase 1NCT01097512
AS703569 and Gemcitabine Combination in Advanced Malignancies
A Phase 1 study testing AS703569/gemcitabine in people with Pancreatic Cancer, run by Merck KGaA, Darmstadt, Germany at 3 sites in 2 countries.
Trial summary
In clinical practice and research, combination of anticancer agents is often used to improve efficacy of treatment. In vitro and in vivo experiments have shown additive-synergistic anti-tumour effects of AS703569 treatment when combined with gemcitabine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- AS703569/gemcitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Jun 2007to Feb 2011
- Phase
- Phase 1
- 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
- Histologically/cytologically confirmed diagnosis of measurable or assessable malignancy, who meets one of the following conditions:
- Subject with a tumour for which gemcitabine is approved, Subject with a tumour for which gemcitabine is considered standard of care, Subject with other tumour type either refractory or intolerant to or for whom there is not an accepted standard treatment.
- Male or female with at least 18 years of age. Life expectancy of at least 3 months.
- Eastern Cooperative Oncology Group (ECOG) Performance Status < 2.
- No more than 3 prior chemotherapy regimens for advanced/metastatic disease.
- At least 4 weeks since last chemotherapy, hormonal therapy, immunotherapy, biological or any other pharmacological or investigational treatment or radiotherapy (6 weeks wash-out for nitrosoureas and mitomycin C, 5 half-lives for non-cytotoxics). Subjects on chronic hormonal therapy may continue with the same treatment unchanged.
- Adequate renal, hepatic and bone marrow functions (assessed 7 days before inclusion in the trial) as defined by:
- Serum creatinine
Who cannot join
None listed.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
France2 sites
Service Inter-Hospitalier de Canderologie Bichat-Beaujon (SIHC) Hopital Beaujon
Clichy, 92118
Unite d'Oncologie Medicale Hopital COCHIN
Paris, 75679
About this study
Official title: A Phase I, Dose-escalation Study of a Combination AS703569 and Gemcitabine Given to Subjects With Advanced Malignancies
In clinical practice and research, combination of anticancer agents is often used to improve efficacy of treatment. In vitro and in vivo experiments have shown additive-synergistic anti-tumour effects of AS703569 treatment when combined with gemcitabine. Specifically, additive-synergistic anti-tumour effects were noticed when the two agents were given sequentially and not concomitantly i.e. AS703569 given the day before or the day after gemcitabine. This trial was designed to investigate in parallel two regimens testing sequential administration of AS703569 either the day after gemcitabine infusion, (Regimen 1) or the day before (Regimen 2).
- Conditions
- Pancreatic Cancer
- Being tested
- AS703569/gemcitabine
- Keywords
- AS703569, MSC1992371A, Aurora kinase inhibitor, Cancer treatable with 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.
AS703569/gemcitabineDrug
Also called Aurora kinase inhibitor, MSC1992371A
Gemcitabine on Days 1 and 8, AS703569 on Days 2 and 9, of a 21-day cycle. The starting dose (DL1) for AS703569 will be 10mg/m2/day. The subsequent dose levels of AS703569 will follow the dose-escalation scheme with an approximate 50% increase from DL1 to DL2, 40% from DL2 to DL3, and thereafter an approximate increase of 33% from one dose level to the next.
Gemcitabine will be administered at the dose of 1000mg/m2 once weekly during the first two weeks of each 21-day cycle.
AS703569/gemcitabineDrug
Also called Aurora kinase inhibitor, MSC1992371A
AS703569 on Days 1 and 8, gemcitabine on Days 2 and 9, of a 21-day cycle. The starting dose (DL1) for AS703569 will be 10mg/m2/day. The subsequent dose levels of AS703569 will follow the dose-escalation scheme with an approximate 50% increase from DL1 to DL2, 40% from DL2 to DL3, and thereafter an approximate increase of 33% from one dose level to the next.
Gemcitabine will be administered at the dose of 1000mg/m2 once weekly during the first two weeks of each 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Regimen 1: AS703569/gemcitabine | Experimental | Gemcitabine on Days 1 and 8, AS703569 on Days 2 and 9, of a 21-day cycle Receives: Drug: AS703569/gemcitabine |
| Regimen 2: AS703569/gemcitabine | Experimental | AS703569 on Days 1 and 8, gemcitabine on Days 2 and 9, of a 21-day cycle Receives: Drug: AS703569/gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
To determine the maximum tolerated dose (MTD) during a 21-day cycle, for each of the two planned regimens using combination therapy with AS703569 and gemcitabine.
Measured: 21 days
Secondary outcomes (6)
Treatment-emergent adverse events (TEAE)
Proportion/number of subjects with TEAE's during the first and subsequent treatment cycles in each cohort for each of the 2 regimens.
Measured: Minimum 21 days or 1 cycle
Progression-Free Survival (PFS) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)
PFS time is defined as time (in months) from first drug intake to date of progression as reported and documented by the investigator (i.e. radiological progression per Response Evaluation Criteria in Solid Tumors [RECIST] criteria) or death from any cause.
Measured: Variable
Time to Tumor Progression (TTP) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)
TTP time is defined as the time (in months)from first drug intake to the date of progression, as reported and documented by the Investigator (i.e. radiological progression per RECIST).
Measured: Variable
Overall Survival (OS) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)
OS time is defined as the time (in months) from first drug intake to any cause of death.
Measured: Variable
Progressive disease (PD)
Proportion of patients with progressive disease as assessed at the end of every other cycle according to disease-specific guidelines
Measured: Every other cycle
Best overall response (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)
For subjects with locally advanced /metastatic pancreatic cancer:
Best overall response: presence of at least one confirmed Complete Response (CR) or confirmed Partial Response (PR) (using RECIST v1.0) during treatment in the 2 regimens as assessed at the end of every other cycle.
Measured: Every other cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2010 (estimated)
- Study startJun 2007
- Primary completionJul 2010
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Narmyn Rejeb, MD, Study director, Merck Serono S.A., Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01097512
- Sponsor's protocol ID
- 27902
- Status last verified
- Jan 2014
- First submitted
- 31 Mar 2010
- Last updated
- 30 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Raymond E, Alexandre J, Faivre S, Goldwasser F, Besse-Hammer T, Gianella-Borradori A, Jego V, Trandafir L, Rejeb N, Awada A. A phase I schedule dependency study of the aurora kinase inhibitor MSC1992371A in combination with gemcitabine in patients with solid tumors. Invest New Drugs. 2014 Feb;32(1):94-103. doi: 10.1007/s10637-013-9950-y. Epub 2013 Mar 29.
PubMed 23539344
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Dose-escalation Study of a Combination AS703569 and Gemcitabine Given to Subjects With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT01097512
- Acronym / sponsor ID
- 27902
- Conditions
- Pancreatic Cancer
- Keywords
- AS703569, MSC1992371A, Aurora kinase inhibitor, Cancer treatable with gemcitabine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- Jun 2007
- Primary completion
- Jul 2010 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 1 Apr 2010 (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.
In clinical practice and research, combination of anticancer agents is often used to improve efficacy of treatment. In vitro and in vivo experiments have shown additive-synergistic anti-tumour effects of AS703569 treatment when combined with gemcitabine. Specifically, additive-synergistic anti-tumour effects were noticed when the two agents were given sequentially and not concomitantly i.e. AS703569 given the day before or the day after gemcitabine. This trial was designed to investigate in parallel two regimens testing sequential administration of AS703569 either the day after gemcitabine infusion, (Regimen 1) or the day before (Regimen 2).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Regimen 1: AS703569/gemcitabine | Experimental | Drug: AS703569/gemcitabineGemcitabine on Days 1 and 8, AS703569 on Days 2 and 9, of a 21-day cycle |
| Regimen 2: AS703569/gemcitabine | Experimental | Drug: AS703569/gemcitabineAS703569 on Days 1 and 8, gemcitabine on Days 2 and 9, of a 21-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically/cytologically confirmed diagnosis of measurable or assessable malignancy, who meets one of the following conditions:
- Subject with a tumour for which gemcitabine is approved, Subject with a tumour for which gemcitabine is considered standard of care, Subject with other tumour type either refractory or intolerant to or for whom there is not an accepted standard treatment.
- Male or female with at least 18 years of age. Life expectancy of at least 3 months.
- Eastern Cooperative Oncology Group (ECOG) Performance Status < 2.
- No more than 3 prior chemotherapy regimens for advanced/metastatic disease.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| AS703569/gemcitabineAlso: Aurora kinase inhibitor, MSC1992371AGemcitabine on Days 1 and 8, AS703569 on Days 2 and 9, of a 21-day cycle. The starting dose (DL1) for AS703569 will be 10mg/m2/day. The subsequent dose levels of AS703569 will follow the dose-escalation scheme with an approximate 50% increase from DL1 to DL2, 40% from DL2 to DL3, and thereafter an approximate increase of 33% from one dose level to the next. Gemcitabine will be administered at the dose of 1000mg/m2 once weekly during the first two weeks of each 21-day cycle. | Drug | Regimen 1: AS703569/gemcitabine |
| AS703569/gemcitabineAlso: Aurora kinase inhibitor, MSC1992371AAS703569 on Days 1 and 8, gemcitabine on Days 2 and 9, of a 21-day cycle. The starting dose (DL1) for AS703569 will be 10mg/m2/day. The subsequent dose levels of AS703569 will follow the dose-escalation scheme with an approximate 50% increase from DL1 to DL2, 40% from DL2 to DL3, and thereafter an approximate increase of 33% from one dose level to the next. Gemcitabine will be administered at the dose of 1000mg/m2 once weekly during the first two weeks of each 21-day cycle. | Drug | Regimen 2: AS703569/gemcitabine |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: 21 days
To determine the maximum tolerated dose (MTD) during a 21-day cycle, for each of the two planned regimens using combination therapy with AS703569 and gemcitabine.
6 secondary outcomes
Treatment-emergent adverse events (TEAE)
Time frame: Minimum 21 days or 1 cycle
Progression-Free Survival (PFS) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)
Time frame: Variable
Time to Tumor Progression (TTP) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)
Time frame: Variable
Overall Survival (OS) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)
Time frame: Variable
Progressive disease (PD)
Time frame: Every other cycle
Best overall response (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)
Time frame: Every other cycle
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2014.
- Results publication: PubMed 23539344Raymond E, Alexandre J, Faivre S, Goldwasser F, Besse-Hammer T, Gianella-Borradori A, Jego V, Trandafir L, Rejeb N, Awada A. A phase I schedule dependency study of the aurora kinase inhibitor MSC1992371A in combination with gemcitabine in patients with solid tumors. Invest New Drugs. 2014 Feb;32(1):94-103. doi: 10.1007/s10637-013-9950-y. Epub 2013 Mar 29.
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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.
Narmyn Rejeb, MD study director
Merck Serono S.A., Geneva
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AS703569/gemcitabine in people with Pancreatic Cancer, run by Merck KGaA, Darmstadt, Germany at 3 sites in 2 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 8 inclusion and 0 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 30 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France, Belgium. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose (MTD) (time frame: 21 days). 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 NCT01097512, 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 30 Jan 2014.