A Phase IIa, Open-Label, Dose-Escalating Study to Evaluate the Safety of AV-951 in Combination with Everolimus in Subjects with Metastatic Renal Cell Carcinoma - ND
- Conditions
- Metastatic Renal Cell CarcinomaMedDRA version: 9.1Level: LLTClassification code 10050513Term: Metastatic renal cell carcinoma
- Registration Number
- EUCTR2009-009461-33-IT
- Lead Sponsor
- AISAR ASSOCIAZIONE ITALIANA PER LO STUDIO DEGLI ANTIMICROBICI E DELLE RESISTENZE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
1.≥ 18-year-old males or females
2.Histologically confirmed renal cell carcinoma.
3.Documented metastatic disease
4.Clinical and laboratory data that at discretion of the investigator allow to perform contrast enhancement CT scan
5.Measurable disease by RECIST criteria (see Appendix A)
6.No more than 1 prior VEGF receptor targeted therapy; no prior treatment with everolimus (RAD-001; Certican) or other drugs targeting the mTOR pathway
7.ECOG performance < 2 and life expectancy ≥ 6 months (see Appendix B)
8.Signed and dated informed consent
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
1.Primary CNS malignancies; active CNS metastases
2.Hematologic malignancies (including leukemia in any form, lymphoma, and multiple myeloma)
3.Any of the following hematologic abnormalities:Hemoglobin < 8.5 g/dL,ANC < 1500 per mm3,Platelet count < 100,000 per mm3
4.Any of the following serum chemistry abnormalities:Total bilirubin > 1.5 × ULN,AST or ALT > 2.5 × ULN (or > 5 x ULN for subjects with liver metastasis),GGT > 2.5 x ULN (or > 5 x ULN for subjects with liver metastasis),Alkaline Phosphatase > 2.5 x ULN (or > 5 x ULN for subjects with liver or bone metastasis),Serum albumin < 3.0 g/dL,Creatinine > 1.5 × ULN,Proteinuria > 2.5 g/24 hours or 3+ with urine dipstick,Any other ≥ Grade 3 laboratory abnormality at baseline (other than those listed above)
5.Significant cardiovascular disease, including:Active clinically symptomatic left ventricular failure,Active hypertension (diastolic blood pressure > 100 mmHg).Subjects with a history of hypertension must have been on stable doses of anti-hypertensive drugs for ≥ 4 weeks,Uncontrolled hypertension:Blood pressure >140/90 mmHg on 2 or more antihypertensive medications,Myocardial infarction within 3 months prior to administration of first dose of study drug
6.Subjects with delayed healing of wounds, ulcers, and/or bone fractures
7.Known pulmonary hypertension or pneumonitis
8.Serious/active infection or infection requiring parenteral antibiotics
9.Inadequate recovery from any prior surgical procedure or major surgical procedure within 6 weeks prior to administration of first dose of study drug
10.Inability to comply with protocol requirements
11.Ongoing hemoptysis or history of clinically significant bleeding
12.Cerebrovascular accident within 12 months prior to administration of first dose of study drug , peripheral vascular disease with claudication on walking less than 1 block, life-threatening lingual angioedema or history of clinically significant angioedema
13.Deep venous thrombosis or pulmonary embolus within 6 months prior to administration of first dose of study drug and/or ongoing need for full-dose oral or parenteral anticoagulation
14.Subjects with a ?currently active? second primary malignancy other than non-melanoma skin cancers. Subjects are not considered to have a ?currently active? malignancy if they have completed anti-cancer therapy and are considered by their physician to be < 30% risk of relapse.
15.Pregnant or lactating women (a pregnancy test is required at screening); all male and female fertile subjects must use adequate contraception (barrier method) while on study and for 3 months thereafter. (Note: Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are not considered effective for this study.)
16.Known concomitant genetic or acquired immune suppression disease such as HIV
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): To determine the safety, tolerability, and maximum tolerated dose of AV-951 when administered in combination with everolimus;Main Objective: To determine the safety, tolerability, and maximum tolerated dose of AV-951 when administered in combination with everolimus;Secondary Objective: To characterize the serum concentration of AV-951 and everolimus when administered alone (AV-951) and in combination.<br>To evaluate the antineoplastic activity of AV-951 and everolimus when administered in combination
- Secondary Outcome Measures
Name Time Method