GLPG0187: Safety, Tolerability and Pharmacokinetics in Patients With Solid Tumors

Solid Tumors Clinical Trial

Official title:

An Open-label, Dose Escalating Phase Ib Study for the Assessment of Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Intravenous Doses of GLPG0187 in Subjects With Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01313598
• Other study ID #: GLPG0187-CL-102
• Secondary ID: 2010-021164-15
• Status: Completed
• Phase: Phase 1
• First received: February 28, 2011
• Last updated: June 9, 2013
• Start date: March 2011
• Est. completion date: June 2013

Study information

• Verified date: June 2013
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine the safety and tolerability of GLPG0187 administered through continuous intravenous infusion and to explore its preliminary clinical efficacy in patients with solid tumors.

Description:

Patients with pathologically confirmed diagnosis of advanced, recurrent, or metastatic cancer and who are refractory to standard therapy or for whom no standard therapy exists will first receive a one-hour infusion of a defined dose of GLPG0187. If well tolerated, one week later a three-week continuous infusion is started. If according to the investigator a subject has a clinical benefit from treatment with GLPG0187, the treatment cycle may be repeated until disease progression, Dose Limiting Toxicity (DLT), or the patient chooses to stop or cannot/will not comply with study procedures.

Throughout treatment, safety and tolerability will be monitored. Within one patient, a fixed dose (infusion rate) will be used. If at a given dose-level sufficient patients have been treated without reaching DLT, the dose for the next group of patients will be increased. This can be repeated until DLT is established, or the scheduled maximum dosage is reached.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically confirmed diagnosis of advanced, recurrent, or metastatic cancer who are refractory to standard therapy or for whom no standard therapy exist.

• Age of 18 years or older.

• Measurable (according to RECIST 1.1) and evaluable disease as determined by the Investigator.

• ECOG Performance Status = 2.

• Estimated life expectancy of at least 12 weeks.

• Toxicities incurred as a result of previous anticancer therapy (radiation therapy, chemotherapy, or surgery) must be resolved to = Grade 2.

• Written informed consent according to local guidelines.

Exclusion Criteria:

• Prior Treatment:

• Less than 4 weeks since the last treatment with other cancer therapies, (i.e. endocrine therapy, immunotherapy, chemotherapy, etc.), and < 6 weeks for nitrosoureas and Mitomycin C.

• Prior therapy with integrin receptor antagonists

• Current Treatment:

• Chronic daily treatment with corticosteroids (dose of 10 mg/day or more methylprednisolone or equivalent), with the exception of inhaled steroids.

• Current or recent (within 30 days of first study treatment) treatment with another investigational drug or participation in another investigational study.

• Hematology, coagulation and biochemistry:

• Inadequate bone marrow function: Absolute Neutrophil Count (ANC): < 1.5 x 10E9/L, or platelet count <100 x 10E9/L or hemoglobin < 6 mmol/L.

• Inadequate liver function, defined as:

• Serum (total) bilirubin > 2 x the Upper Limit of Normal (ULN) for the institution;

• Aspartate Amino Transferase (ASAT) or Alanine Amino Transferase (ALAT) > 2.5 x ULN (> 5 x ULN in subjects with liver metastases);

• Alkaline phosphatase levels > 2.5 x ULN (> 5 x ULN in subjects with liver metastases, or > 10 x ULN in subjects with bone metastases).

• Inadequate renal function, defined as:

• Serum creatinine > 1.5 x ULN

• Urine dipstick for proteinuria > 2+.

• Other:

• Clinically symptomatic or progressive brain metastases

• Clinical Leptomeningeal metastases

• Pregnancy or lactation. Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start.

• For women of childbearing potential (defined as <2 years after last menstruation and not surgically sterile): absence of effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel).

• Major surgical procedure (including open biopsy, excluding central line IV and portacath) within 28 days prior to the first study treatment, or anticipation of the need for major surgery during the course of the study treatment.

• Congestive heart failure NYHA Class III and IV. Cardiac arrhythmias (except for atrioventricular block type I, Mobitz type, and II, Wenckebach type) signs and symptoms of relevant cardiovascular disease.

• Known hypersensitivity to any of the study drugs or excipients.

• Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, physical examination or laboratory findings) that may interfere with the planned treatment, affect subject compliance or place the subject at high risk from treatment-related complications.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• GLPG0187
continuous IV infusion

Locations

Country	Name	City	State
Netherlands	Nationaal Kanker Instituut (NKI)	Amsterdam
Netherlands	Universitair Medisch Centrum	Utrecht

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability	Patients will be monitored for cardiovascular safety (ECG) and adverse events, and blood- and urine-samples taken before and at fixed timepoints after a one-hour infusion of GLPG0187; if patients tolerate the treatment well, procedures will be repeated before and at fixed timepoints after the start of a three-week continuous infusion patients. Through monitoring and analysis of the blood- and urine-samples, it will be established whether the study medication would have any negative effects on the patient's general condition. Results will indicate whether DLT has occurred.	Four weeks + three-week cycles	Yes
Secondary	Pharmacokinetics of GLPG0187 after intravenous infusion.	Blood samples will be taken at regular timepoints before and on fixed timepoints after start of the one-hour infusion, as well as before and on fixed timepoints during the (first) three-week infusion, to establish the concentration of the study medication in the blood.	Up to four weeks.	No
Secondary	Pharmacodynamics of GLPG0187	Blood samples will be taken at regular timepoints before and on fixed timepoints after start of the one-hour infusion, as well as before and on fixed timepoints during the (first) three-week infusion, to measure the levels of CTx (collagen telopeptide, a bone resorption biomarker).	Up to four weeks	No
Secondary	Preliminary efficacy of GLPG0187 in terms of clinical activity.	evaluation of antitumor effects according to RECIST 1.1.	Four weeks + three-week cycles	No