Study of the Combination of Axitinib Plus Everolimus in Patients With Malignant Advanced Solid Tumors

• Status: Completed
• Trial end date: 2015-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The aim of the study is to determine the MTD of the combination of everolimus plus axitinib in solid tumors, especially RCC.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Bordeaux
• Treatments: Axitinib; Everolimus; Sirolimus

Criteria

Inclusion criteria

• Histologically proven advanced adult solid tumors, with the exception of Hodgkin and non Hodgkin lymphoma. Patients with hepatocellular carcinomas (HCC) may be enrolled without histological documentation if they meet the consensus non-invasive diagnostic criteria.

• Failure or contra-indication of all standard therapies, except for the patients with advanced renal cell carcinoma, enrolled at the recommended dose who will be naïve of previous lines of therapy while metastatic.

• Age > 18 years

• ECOG Performance status (PS) 0-1

• Life expectancy > 3 months

• Measurable/evaluable disease according to RECIST CRITERIA version 1.0

• Acceptable biological values: Hemoglobin > 10g /dL; neutrophils > 1.5 x 109/L; platelets > 100 x 109/L, AST and ALT < 2.5 x the upper normal limits (UNL), or < 5 x UNL in case of liver metastases, GGT < 3 x the upper normal limits (UNL), PAL < 2.5 x the upper normal limits (UNL), or < 5 x UNL in case of liver metastases, serum bilirubin < 1.5 x ULN, creatinine clearance (Cockroft & Gault formula) > 60 mL/min.

• 24 hours proteinuria ≤ 1 g/24 h

• Albumin > 30 g/l

• Amylase and lipase ≤ 1.5 UNL

• Electrolytes (calcium, sodium, potassium, chlore, magnesium, phosphate) in the normal range. Supplementation could be possible before study entry.

• Total cholesterol ≤ 2.5 UNL

• Triglycerides ≤ 2.5 UNL

• BP < 140/90

• Washout period from last anticancer therapy, including radiation and surgery > 3 weeks and recovery of toxicities to NCI-CTC grade < 1.

• Written informed Consent.

• Use of effective contraceptive method (Intrauterine device, oral combined contraceptive) for women of child-bearing age or whose partner is included in the trial.

• Patient with french social security.

• Additional inclusion criteria before the association axitinib plus everolimus period

• No toxicity with NCI-CTC grade > 2 at the end of axitinib alone period just before starting axitinib and everolimus (cycle 1)

• BP < 140/ 90

Exclusion criteria

• Brain metastasis

• Severe underlying cardiovascular disease, even medically controlled, such as angina pectoris, myocardial infarction, cardiac insufficiency, cardiac failure, cerebral strokes, lower limb ischemic disease, thromboembolic disease, and any patient, who, in the investigator's opinion is at high risk for arterial or venous thromboembolism.

• Hepatitis B or C carrier or at a chronic state

• Uncontrolled hypertension, or diabetes mellitus despite medical treatment.

• Inability to swallow pills

• Unresolved pneumopathy, no need for antibiotherapy

• Any medical or social condition, which; in the investigator's opinion, would jeopardize patient's safety, patient's compliance to the protocol, or the interpretation of study results. These conditions include (but are not limited to): severe infection, cardiac failure, chronic gastrointestinal disease compromising oral drug absorption, psychiatric illnesses, foreseeable poor treatment compliance with oral medications, patients living far away from the investigational centers, etc…

• Hypersensitivity to Axitinib or Everolimus

• Participation to another clinical trial, or use of an unapproved medication within 4 weeks prior to study treatment initiation.

• Pregnant or lactating women.