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

NCT01334073 | Completed Phase 1 DMC

• 2 other identifiers: CHUBX 2010/092010-021280-32
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Malignant Advanced Solid Tumors; Carcinoma, Renal Cell

Keywords

Phase I; Axitinib; Everolimus; Maximum tolerated dose (MTD); solid tumor; Renal cell cancer (RCC); Pharmacokinetics (PK/PD)

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with DLT (dose limiting toxicity) during the first cycle (first 28 days of the combination of both study compounds), per dose level explored

  A DLT will be one of the following adverse events, with a possible relationship to the study medications * Febrile, related bleeding or any grade 4 neutropenia or thrombocytopenia, * grade 3 non-hematological toxicity, unless adequately treated with usual symptomatic therapy * grade 4 non-hematological toxicity * study treatment interruption \> 2 weeks, inability to deliver at least 80% of the intended doses of axitinib and/or everolimus between day 8 and 35 due to toxicity.

  during cycle 1

Secondary Outcomes (5)

• Adverse event (AE) will be graded according to NCI-CTC criteria V3

  After each cycle of treatement

• Best response rate will be assessed according to RECIST criteria, during the follow-up

  Every other cycle of treatment

• Rate of non-tumor progression at 16 weeks

  at 16 weeks

• Progression-free Survival (PFS) defined as the time between study treatment initiation and either tumor progression or death, regardless of the cause, whichever occurs first and PFS at 1 year

  1 year

• Comparison of PK parameters

  day 1 (axitinib alone) and day 15 (everolimus combined with axitinib)

Study Arms (1)

Axitinib plus everolimus

EXPERIMENTAL

Drug: Axitinib plus everolimus

Interventions

Axitinib plus everolimus DRUG

Patients will take both drugs orally, every day, without planned rest period (AX bid and EV once a day). By convention one cycle is 28 days. At the first cycle patients will take one week of AX single agent before starting EV. Patients will be treated at increasing dose levels (DLs) in successive cohorts of 3-6 patients according to the number of patients with dose limiting toxicities (DLT) until the maximum tolerated dose

Axitinib plus everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (2)

Professeur Alain RAVAUD

Bordeaux, 33000, France

Location

Professeur Jean-Pierre DELORD

Toulouse, 31000, France

Location

Related Publications (4)

• Su Y, Amiri KI, Horton LW, Yu Y, Ayers GD, Koehler E, Kelley MC, Puzanov I, Richmond A, Sosman JA. A phase I trial of bortezomib with temozolomide in patients with advanced melanoma: toxicities, antitumor effects, and modulation of therapeutic targets. Clin Cancer Res. 2010 Jan 1;16(1):348-57. doi: 10.1158/1078-0432.CCR-09-2087. Epub 2009 Dec 22.

  PMID: 20028756 BACKGROUND

• O'Reilly T, Lane HA, Wood JM, Schnell C, Littlewood-Evans A, Brueggen J, McSheehy PM. Everolimus and PTK/ZK show synergistic growth inhibition in the orthotopic BL16/BL6 murine melanoma model. Cancer Chemother Pharmacol. 2011 Jan;67(1):193-200. doi: 10.1007/s00280-010-1307-z. Epub 2010 May 30.

  PMID: 20512579 BACKGROUND

• Choueiri TK. Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. Curr Opin Investig Drugs. 2008 Jun;9(6):658-71.

  PMID: 18516765 BACKGROUND

• Ravaud A, Gomez-Roca C, Picat MQ, Digue L, Chevreau C, Gimbert A, Chauzit E, Sitta R, Cornelis F, Asselineau J, Aziza R, Daste A, Quemener C, Baud J, Bikfalvi A, Pedenon-Perichout D, Doussau A, Molimard M, Delord JP. Phase I study of axitinib and everolimus in metastatic solid tumours and extension to metastatic renal cell carcinoma: Results of EVAX study. Eur J Cancer. 2017 Nov;85:39-48. doi: 10.1016/j.ejca.2017.07.031. Epub 2017 Sep 5.

  PMID: 28886476 RESULT

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Axitinib; Everolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Sirolimus; Macrolides; Lactones

Study Officials

• Alain RAVAUD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Adélaïde Doussau, Dr

  University Hospital, Bordeaux

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2011
• First Posted: April 12, 2011
• Study Start: March 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: January 1, 2015
• Last Updated: May 14, 2026

Record last verified: 2015-07

Locations

FR (2)