Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

AS703569 and Gemcitabine Combination in Advanced Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01097512
First received: March 31, 2010
Last updated: January 29, 2014
Last verified: January 2014

March 31, 2010
January 29, 2014
June 2007
July 2010   (final data collection date for primary outcome measure)
Maximum tolerated dose (MTD) [ Time Frame: 21 days ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01097512 on ClinicalTrials.gov Archive Site
  • Treatment-emergent adverse events (TEAE) [ Time Frame: Minimum 21 days or 1 cycle ] [ Designated as safety issue: No ]
    Proportion/number of subjects with TEAE's during the first and subsequent treatment cycles in each cohort for each of the 2 regimens.
  • Progression-Free Survival (PFS) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part) [ Time Frame: Variable ] [ Designated as safety issue: No ]
    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 to Tumor Progression (TTP) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part) [ Time Frame: Variable ] [ Designated as safety issue: No ]
    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).
  • Overall Survival (OS) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part) [ Time Frame: Variable ] [ Designated as safety issue: No ]
    OS time is defined as the time (in months) from first drug intake to any cause of death.
  • Progressive disease (PD) [ Time Frame: Every other cycle ] [ Designated as safety issue: No ]
    Proportion of patients with progressive disease as assessed at the end of every other cycle according to disease-specific guidelines
  • Best overall response (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part) [ Time Frame: Every other cycle ] [ Designated as safety issue: No ]

    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.

  • Treatment-emergent adverse events (TEAE) [ Time Frame: Minimum 21 days or 1 cycle ] [ Designated as safety issue: No ]
    Proportion/number of subjects with TEAE's during the first and subsequent treatment cycles in each cohort for each of the 2 regimens.
  • Progression-Free Survival (PFS) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part) [ Time Frame: Variable ] [ Designated as safety issue: No ]
    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 RECIST criteria) or death from any cause.
  • 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 ] [ Designated as safety issue: No ]
    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).
  • Overall Survival (OS) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part) [ Time Frame: Variable ] [ Designated as safety issue: No ]
    OS time is defined as the time (in months) from first drug intake to any cause of death.
  • Progressive disease (PD) [ Time Frame: Every other cycle ] [ Designated as safety issue: No ]
    Proportion of patients with progressive disease as assessed at the end of every other cycle according to disease-specific guidelines
  • Best overall response (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part) [ Time Frame: Every other cycle ] [ Designated as safety issue: No ]

    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.

Not Provided
Not Provided
 
AS703569 and Gemcitabine Combination in Advanced Malignancies
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).

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Pancreatic Cancer
  • 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.

    Other Names:
    • Aurora kinase inhibitor
    • MSC1992371A
  • Drug: AS703569/gemcitabine

    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.

    Other Names:
    • Aurora kinase inhibitor
    • MSC1992371A
  • Experimental: Regimen 1: AS703569/gemcitabine
    Gemcitabine on Days 1 and 8, AS703569 on Days 2 and 9, of a 21-day cycle
    Intervention: Drug: AS703569/gemcitabine
  • Experimental: Regimen 2: AS703569/gemcitabine
    AS703569 on Days 1 and 8, gemcitabine on Days 2 and 9, of a 21-day cycle
    Intervention: Drug: AS703569/gemcitabine
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. 2013 Mar 29. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
66
February 2011
July 2010   (final data collection date for primary outcome measure)

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

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Belgium,   France
 
NCT01097512
27902
No
Merck KGaA
Merck KGaA
Not Provided
Study Director: Narmyn Rejeb, MD Merck Serono S.A., Geneva
Merck KGaA
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP