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.
- Conditions
- solid neoplasmsolid tumors10027655
- Registration Number
- NL-OMON36388
- Lead Sponsor
- Galapagos SAS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 19
1. Pathologically confirmed diagnosis of advanced, recurrent, or metastatic cancer who are refractory to standard therapy or for whom no standard therapy exist.
2. Age >= 18 years.
3. Measurable (according to RECIST 1.1) and evaluable disease as determined by the Investigator.
4. ECOG Performance Status <= 2.
5. Estimated life expectancy of at least 12 weeks.
6. Toxicities incurred as a result of previous anticancer therapy (radiation therapy, chemotherapy, or surgery) must be resolved to <= Grade 2.
7. Written informed consent according to local guidelines.
Prior Treatment:
1. 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.
2. Prior therapy with integrin receptor antagonists.;Current Treatment:
3. Chronic daily treatment with corticosteroids (dose of * 10 mg/day methylprednisolone or equivalent), with the exception of inhaled steroids.
4. 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:
5. Inadequate bone marrow function: Absolute Neutrophil Count (ANC): < 1.5 x 109/L, or platelet count <100 x 109/L or hemoglobin < 6 mmol/L.
6. 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).
7. Inadequate renal function, defined as:
• Serum creatinine > 1.5 x ULN
• Urine dipstick for proteinuria > 2+.;Other:
8. Clinically symptomatic or progressive brain metastases
9. Clinical Leptomeningeal metastases
10. Pregnancy or lactation. Urine pregnancy test to be assessed within 7 days prior to study treatment start.
11. 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).
12. 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.
13. 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.
14. Known hypersensitivity to any of the study drugs or excipients.
15. 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
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The incidence rate of DLTs at each dose level based on the following safety<br /><br>parameters: Adverse drug reactions (ADR) and serious ADRs, changes in<br /><br>hematology and chemistry values, including those associated with hepatic and<br /><br>renal function, and assessment of physical examinations, vital signs and<br /><br>cardiac function (i.e. repeated electrocardiograms). NCI-CTCAE version 4.03<br /><br>will be used.</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Exposure to GLPG0187 in plasma;<br /><br>• Effects of GLPG0187 on bone resorption biomarker;<br /><br>• Preliminary efficacy: Antitumor effects of GLPG0187 according to RECIST 1.1.</p><br>