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
  Purpose

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).


Condition Intervention Phase
Pancreatic Cancer
Drug: AS703569/gemcitabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Dose-escalation Study of a Combination AS703569 and Gemcitabine Given to Subjects With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.



Enrollment: 66
Study Start Date: June 2007
Study Completion Date: February 2011
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen 1: AS703569/gemcitabine
Gemcitabine on Days 1 and 8, AS703569 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.

Other Names:
  • Aurora kinase inhibitor
  • MSC1992371A
Experimental: Regimen 2: AS703569/gemcitabine
AS703569 on Days 1 and 8, gemcitabine 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. 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01097512

Locations
Belgium
Institut Jules Bordet
Bruxelles, Belgium, 1000
France
Service Inter-Hospitalier de Canderologie Bichat-Beaujon (SIHC) Hopital Beaujon
Clichy, France, 92118
Unite d'Oncologie Medicale Hopital COCHIN
Paris, France, 75679
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Narmyn Rejeb, MD Merck Serono S.A., Geneva
  More Information

Publications:
Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01097512     History of Changes
Other Study ID Numbers: 27902
Study First Received: March 31, 2010
Last Updated: January 29, 2014
Health Authority: Belgium: Institutional Review Board
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Merck KGaA:
AS703569
MSC1992371A
Aurora kinase inhibitor
Cancer treatable with gemcitabine

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on April 17, 2014