AS703569 and Gemcitabine Combination in Advanced Malignancies

Pancreatic Cancer Clinical Trial

Official title:

A Phase I, Dose-escalation Study of a Combination AS703569 and Gemcitabine Given to Subjects With Advanced Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01097512
• Other study ID #: 27902
• Status: Completed
• Phase: Phase 1
• First received: March 31, 2010
• Last updated: January 29, 2014
• Start date: June 2007
• Est. completion date: February 2011

Study information

• Verified date: January 2014
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Institutional Review BoardFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: February 2011
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Bruxelles
France	Service Inter-Hospitalier de Canderologie Bichat-Beaujon (SIHC) Hopital Beaujon	Clichy
France	Unite d'Oncologie Medicale Hopital COCHIN	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Countries where clinical trial is conducted

Belgium,  France, 

References & Publications (1)

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 so — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	21 days	No
Secondary	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.	Minimum 21 days or 1 cycle	No
Secondary	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.	Variable	No
Secondary	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).	Variable	No
Secondary	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.	Variable	No
Secondary	Progressive disease (PD)	Proportion of patients with progressive disease as assessed at the end of every other cycle according to disease-specific guidelines	Every other cycle	No
Secondary	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.	Every other cycle	No