A Phase 1 interventional study of AS703569/gemcitabine and AS703569/gemcitabine in Pancreatic Cancer, sponsored by Merck KGaA, Darmstadt, Germany. Completed at 3 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-01-30.
Sponsored by Merck KGaA, Darmstadt, Germany · Phase 1, Interventional, and Treatment
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).
Merck KGaA, Darmstadt, Germany is the lead sponsor of 269 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
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
Gemcitabine on Days 1 and 8, AS703569 on Days 2 and 9, of a 21-day cycle
Drug: AS703569/gemcitabine
AS703569 on Days 1 and 8, gemcitabine on Days 2 and 9, of a 21-day cycle
Drug: AS703569/gemcitabine
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.
Also known as: 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.
Also known as: Aurora kinase inhibitor, MSC1992371A
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.
Time frame: 21 days
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.
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)
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.
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)
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).
Time frame: 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.
Time frame: Variable
Progressive disease (PD)
Proportion of patients with progressive disease as assessed at the end of every other cycle according to disease-specific guidelines
Time frame: 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.
Time frame: Every other cycle
This study is completed, as verified in Jan 2014. You cannot join it, but the record below documents what was studied.
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Merck KGaA, Darmstadt, Germany