Clinical trial NCT01097512: AS703569 and Gemcitabine Combination in Advanced Malignancies
Official title: A Phase I, Dose-escalation Study of a Combination AS703569 and Gemcitabine Given to Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Cancer
Keywords: AS703569
MSC1992371A
Aurora kinase inhibitor
Cancer treatable with gemcitabine
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2010-04-01
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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).


Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: 21 days
Secondary outcomes:
measure: Treatment-emergent adverse events (TEAE)
timeFrame: Minimum 21 days or 1 cycle
measure: Progression-Free Survival (PFS) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)
timeFrame: Variable
measure: Time to Tumor Progression (TTP) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)
timeFrame: Variable
measure: Overall Survival (OS) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)
timeFrame: Variable
measure: Progressive disease (PD)
timeFrame: Every other cycle
measure: Best overall response (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)
timeFrame: Every other cycle
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Clichy
country: France
facility: Service Inter-Hospitalier de Canderologie Bichat-Beaujon (SIHC) Hopital Beaujon
city: Paris
country: France
facility: Unite d'Oncologie Medicale Hopital COCHIN
Study officials:
affiliation: Merck Serono S.A., Geneva
name: Narmyn Rejeb, MD
role: STUDY_DIRECTOR
References:
citation: 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.