AS703569 and Gemcitabine Combination in Advanced Malignancies

NCT01097512 | Completed Phase 1

• 1 other identifier: 27902
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 3

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).

Conditions

Pancreatic Cancer

Keywords

AS703569; MSC1992371A; Aurora kinase inhibitor; Cancer treatable with gemcitabine

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• Treatment-emergent adverse events (TEAE)

  Minimum 21 days or 1 cycle

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

  Variable

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

  Variable

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

  Variable

• Progressive disease (PD)

  Every other cycle

Study Arms (2)

Regimen 1: AS703569/gemcitabine

EXPERIMENTAL

Gemcitabine on Days 1 and 8, AS703569 on Days 2 and 9, of a 21-day cycle

Drug: AS703569/gemcitabine

Regimen 2: AS703569/gemcitabine

EXPERIMENTAL

AS703569 on Days 1 and 8, gemcitabine on Days 2 and 9, of a 21-day cycle

Drug: AS703569/gemcitabine

Interventions

AS703569/gemcitabine DRUG

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.

Also known as: Aurora kinase inhibitor, MSC1992371A

Regimen 1: AS703569/gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Serum creatinine

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (3)

Institut Jules Bordet

Brussels, 1000, Belgium

Location

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

Clichy, 92118, France

Location

Unite d'Oncologie Medicale Hopital COCHIN

Paris, 75679, France

Location

Related 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 solid tumors. Invest New Drugs. 2014 Feb;32(1):94-103. doi: 10.1007/s10637-013-9950-y. Epub 2013 Mar 29.

  PMID: 23539344 RESULT

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

MSC1992371A; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Narmyn Rejeb, MD

  Merck Serono S.A., Geneva

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2010
• First Posted: April 1, 2010
• Study Start: June 1, 2007
• Primary Completion: July 1, 2010
• Study Completion: February 1, 2011
• Last Updated: January 30, 2014

Record last verified: 2014-01

Locations

BE (1); FR (2)