Phase I/II study of dalteparin, a low molecular weight heparin (LMWH), in combination with Sunitinib (SU11248), an oral, selective multitargeted tyrosine kinase inhibitor, as first line treatment, in patients with metastatic renal cell carcinoma

Phase 1

• Conditions: Patients with metastatic or inoperable renal cell cancer

• Registration Number: EUCTR2007-002962-37-NL
• Lead Sponsor: VU Medical Center Amsterdam

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-05-12
• Last Update Posted: 8 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

3.1Inclusion Criteria

1)Patients must have histologically confirmed metastatic or unresectable renal cell carcinoma.
2) Clear cell and non-clear renal carcinoma patients are eligible. Oncocytoma, collecting duct tumors and transitional cell carcinoma are NOT eligible.
3)No prior systemic treatments for metastatic disease are permitted, including antiangiogenic therapy, immunotherapy, chemotherapy and investigational therapy.
4)Patients with their primary tumor in place who are appropriate surgical candidates should be strongly encouraged to undergo nephrectomy prior to treatment initiation, based on the potential effect on survival.
6) Prior palliative radiation to metastatic lesion(s) is permitted, provided there is at least one measurable and/or evaluable lesion(s) that has not been radiated.
7) Radiation therapy must be completed >4 weeks prior to registration
8) Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as >20 mm with conventional techniques or as >10 mm with spiral CT scan (RECIST criteria).
9) Age > 18 years.
10) ECOG performance status = 2.
11) Patients must have normal organ and marrow function as defined below:
•leukocytes>3,000/mm3
•absolute neutrophil count>1,500/mm3
•platelets>100,000/mm3
•total bilirubin<1.5 x laboratory upper limit of normal
•AST(SGOT)/ALT(SGPT)<2.5 x laboratory upper limit of normal
•creatinine<1.5 x laboratory upper limit of normal or
measured Creatinine clearance of >50 ml/min/1.73m2
•PT/INR<1.5
•Urine protein<1+; if >1+, 24 hour urine protein should be
obtained and should be <1000 mg

12)The effects of Sunitinib on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because angiogenesis inhibitors are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
13) Ability to understand and the willingness to sign a written informed consent document.
14) The effect of this combination treatment on the risk for hemorrhage is unknown, but it is possible that it is increased. Therefore, except for Dalteparin that will be administered as a study drug, the patients should not take any other anticoagulants or anitiplatelet agents during the study, including but not limited to NSAID (any dose of aspirin), warfarin or other anticoagulants.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1)Prior therapy with Sunitinib.
2)Patients may not be receiving any other investigational agents.
3)Patients with known CNS metastases. Patients should have a head CT/MRI within 14 days prior to treatment initiation. Any imaging abnormality indicative of CNS metastases will exclude the patient from the study.
4)Patients with a currently active” second malignancy other than non-melanoma skin cancers are not eligible. Patients are not considered to have a currently active” malignancy if they have completed anti-cancer therapy and are considered by their physician to be at less than 30% risk of relapse.
5)Patients with a large (>2cm) pulmonary lesion involving the trachea or one of the main bronchus and any endobronchial lesion.
6)History of allergic reactions attributed to compounds of similar chemical or biologic composition to Dalteparin.
7)Evidence of bleeding diathesis within last 6 months.
9)Serious or non-healing wound, ulcer or bone fracture or active peptic ulceration.
10)Current therapeutic full-dose of anticoagulants, either warfarin or LMWH or unfractionated heparin.
11)Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Association Class II, III, or IV), angina pectoris requiring nitrate therapy, recent myocardial infarction (< the last 6 months), cardiac arrhythmia, history of CVA within 6 months (thrombotic or hemorrhagic), hypertension (defined as blood pressure of >160 mmHg systolic and/or >90 mmHg diastolic on medication), hemorrhagic retinopathy, history of peripheral vascular disease, or psychiatric illness/social situations that would limit compliance with study requirements.
12) Patients with an ejection fraction <50% by MUGA scan are not eligible.
13)Pregnant women are excluded from this study because Sunitinib is an angiogenesis inhibitor agent with the potential for teratogenic or abortion inducing effects.
14)History of abdominal fistula, gastrointestinal perforation or intra-abdominal abcess within 28 days prior to day 1 therapy.
15)Invasive procedures defined as:
-Major surgical procedure, open biopsy, or significant traumatic injury within 6 weeks prior to day 1 therapy.
-Anticipation of need for major surgical procedures during the course of the study.
-Core biopsy within 7 days prior to start therapy.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified