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AS703569 and Gemcitabine Combination in Advanced Malignancies

Phase 1
Completed
Conditions
Pancreatic Cancer
Interventions
Drug: AS703569/gemcitabine
Registration Number
NCT01097512
Lead Sponsor
Merck KGaA, Darmstadt, Germany
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
66
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

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Regimen 1: AS703569/gemcitabineAS703569/gemcitabineGemcitabine on Days 1 and 8, AS703569 on Days 2 and 9, of a 21-day cycle
Regimen 2: AS703569/gemcitabineAS703569/gemcitabineAS703569 on Days 1 and 8, gemcitabine on Days 2 and 9, of a 21-day cycle
Primary Outcome Measures
NameTimeMethod
Maximum tolerated dose (MTD)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.

Secondary Outcome Measures
NameTimeMethod
Progression-Free Survival (PFS) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)Variable

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.

Progressive disease (PD)Every other cycle

Proportion of patients with progressive disease as assessed at the end of every other cycle according to disease-specific guidelines

Treatment-emergent adverse events (TEAE)Minimum 21 days or 1 cycle

Proportion/number of subjects with TEAE's during the first and subsequent treatment cycles in each cohort for each of the 2 regimens.

Best overall response (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)Every other cycle

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.

Overall Survival (OS) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)Variable

OS time is defined as the time (in months) from first drug intake to any cause of death.

Time to Tumor Progression (TTP) time (For subjects with locally advanced /metastatic pancreatic cancer included after completion of the dose escalation part)Variable

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).

Trial Locations

Locations (3)

Unite d'Oncologie Medicale Hopital COCHIN

🇫🇷

Paris, France

Service Inter-Hospitalier de Canderologie Bichat-Beaujon (SIHC) Hopital Beaujon

🇫🇷

Clichy, France

Institut Jules Bordet

🇧🇪

Bruxelles, Belgium

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