Biomarkers Before and After Nephrectomy of Locally Advanced or Metastatic Renal Cell Carcinoma Treated With Everolimus (NEORAD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
Sponsor:
Information provided by (Responsible Party):
Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
ClinicalTrials.gov Identifier:
NCT01715935
First received: September 12, 2012
Last updated: October 25, 2012
Last verified: October 2012
  Purpose

Disease and Stage: Metastatic and locally advanced clear cell renal carcinoma

An open-label, exploratory, single-arm, multicenter trial.

Everolimus will be administered orally, once daily, for 6 weeks followed by a 1-week rest period prior to nephrectomy.

Two to four weeks after surgery, everolimus will be reintroduced only for metastatic patients until disease progression, unacceptable toxicity, withdrawal of patient consent, or other stopping rules are met.


Condition Intervention Phase
Clear-cell Renal Carcinoma
Clear-cell Metastatic Renal Cell Carcinoma
Drug: Everolimus
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Comparison of Blood and Tissue Biomarkers Before and After Nephrectomy in the First-line Setting With Everolimus in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie:

Primary Outcome Measures:
  • Objective clinical benefit [ Time Frame: After 6 weeks of treatment ] [ Designated as safety issue: No ]
    Objective clinical benefit is defined as complete response, partial response or stable disease according to RECIST criteria version 1.1


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: Participants will be followed all along the treatment period, an expected average of 15 months ] [ Designated as safety issue: Yes ]
    Toxicity will be classify according to NCI-CTC criteria Version 4.0


Estimated Enrollment: 60
Study Start Date: June 2012
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: everolimus
everolimus, 10 mg PO daily. Before nephrectomy: 6 continuous weeks of treatment and one week of rest After nephrectomy: 4 weeks courses (for metastatic patients only)
Drug: Everolimus
everolimus, 10 mg PO daily. Before nephrectomy: 6 continuous weeks of treatment and one week of rest After nephrectomy: 4 weeks courses (for metastatic patients only)
Other Name: AFINITOR

Detailed Description:

An open-label, exploratory, single-arm, multicenter trial. Treatment with everolimus will be initiated once patients have undergone baseline screening and provided their written informed consent.

Everolimus will be administered orally, once daily, for 6 weeks followed by a 1-week rest period prior to surgery. The starting dose will be 10 mg daily with provision for dose reduction based on tolerability.

Radical nephrectomy will be performed at the end of week 7. For metastatic patients, two to four weeks after surgery, everolimus will be reintroduced. Treatment will be continued until disease progression, unacceptable toxicity, withdrawal of patient consent, or other stopping rules are met.

Patients with locally advanced renal carcinoma will stop drug intake before nephrectomy.

Resumption of everolimus may be postponed in cases of a delay in wound healing or surgical complications.

After treatment discontinuation and the last treatment visit (28-days after the last dose), patients will be followed up in order to collect data on the onset of progression and survival. In metastatic patients discontinuing treatment for reasons other than disease progression, tumor assessment will continue every 3 months, until disease progression or initiation of other anticancer therapy for up to one year of follow-up.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Advanced RCC or a resectable renal tumor and at least one measurable inoperable metastasis (at least 1 cm), in whom anti-angiogenic therapy is indicated
  • Patients without target lesions, with bone metastasis
  • Histologically confirmed clear cells RCC and possibility of adequate tumor sampling prior to treatment
  • No prior systemic treatment for RCC
  • Male or female, at least 18 years
  • PS ECOG 0-1
  • Life expectancy at least 3 months
  • Adequate organ function with the following criteria:

    • Total serum bilirubin equal or less than 2 x ULN (Gilbert's disease exempted)
    • Serum transaminases and alkaline phosphatases equal or less than 2.5 x ULN, or in case of liver or bone metastasis equal or less than 5x ULN
    • Serum creatinine equal or less than 2 x ULN, creatinine clearance at least 50 ml/min
    • Absolute neutrophil count (ANC) at least 1500/mm3
    • Platelets at least 100,000/mm3
    • Hemoglobin at least 10.0 g/dL
    • INR equal or less than 1.7 or prothrombin time (PT) equal or less than 6 sec
    • Blood glucose less than 1.5x ULN
    • Fasting cholesterol equal or less than 5 mmol/L, triglycerides equal or less than 200 mg/dl,
  • Negative pregnancy test within 7 days prior to enrollment
  • Signed and dated IRB/ICE-approved informed consent form
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
  • Patient covered by the national health system

Exclusion Criteria:

  • Previous nephrectomy
  • Histology: any histologic type different than ccRCC
  • Treatment in a clinical trial in the last 30 days
  • Previous treatment with everolimus or other mTOR-inhibitors and anti-angiogenic drugs
  • Any of the following within 12 months prior to treatment initiation: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, ischemic or hemorrhagic stroke including transient ischemic attack, abnormal lung function.
  • Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg, despite optimal medical treatment
  • Abnormal ECG (Clinically significant)
  • Treatment with vitamin K antagonists. Ongoing treatment with therapeutic doses of coumarin derivative anticoagulants (e.g. warfarin) or treatment within the 2 weeks before the first day of everolimus administration. Prophylaxis with low dose warfarin for deep vein thrombosis is permitted (up to 2 mg/day). Low molecular weight heparin is allowed.
  • Brain metastasis. (Brain scan or MRI is mandatory). Note: Previous treated brain metastasis (surgery ± radiotherapy, radiotherapy, radiosurgery or gammaknife) and satisfying the following three criteria are allowed:

    • Asymptomatic;
    • No evidence of any active brain metastasis 3 months prior inclusion;
    • No necessity of corticoid or antiepileptic treatment.
  • Pregnancy or breastfeeding.
  • Any second malignancy within the last 3 years with the exception of basal cell carcinoma, in situ cervical cancer and pT1/a bladder cancer with no evidence of recurrent disease for 12 months.
  • Clinically significant gastrointestinal abnormalities including but not limited to:

    • Malabsorption syndrome
    • Major resection of the stomach or small bowel that could affect the absorption of the study drug
    • Active peptic ulcer disease
    • Inflammatory bowel disease
    • Ulcerative colitis or other gastrointestinal conditions with increased risk of perforation
    • History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment
    • Hepatitis B/C
  • Hypersensitivity to everolimus or any excipient of everolimus.
  • Any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01715935

Contacts
Contact: Reza T Elaidi, PhD 00 33 1 56 09 23 40 reza-thierry.elaidi@egp.aphp.fr
Contact: Corine Takouchop Teghom, MD, MPH 00 33 1 56 09 34 34 corinne.takouchop@egp.aphp.fr

Locations
France
CHRU Besançon Recruiting
Besançon, France, 25000
Contact: Antoine Thiery-Vuillemin, MD    00 33 3 81 66 93 20    a.thieryvuillemin@mac.com   
Principal Investigator: Antoine Thiery-Vuillemin, MD         
Hôpital Henri Mondor Recruiting
Créteil, France, 94000
Contact: Christophe Tournigand, MD       christophe.tournigand@hmn.aphp.fr   
Principal Investigator: Christophe Tournigand, MD         
Centre Hospitalier Départemental Vendée Recruiting
La Roche-sur-Yon, France, 85925 cedex 9
Contact: Frank Priou, MD    00 33 2 51 44 61 73    frank.priou@chd-vendee.fr   
Principal Investigator: Frank Priou, MD         
Hôpital Saint Eloi - CHU Montpellier Recruiting
Montpellier, France, 34285 cedex 5
Contact: Delphine Topart, MD    00 33 04 67 33 23 05    d-topart@chu-montpellier.fr   
Principal Investigator: Delphine Topart, MD         
Hôpital Européen Georges Pompidou - Service d'oncologie médicale Recruiting
Paris, France, 7505
Contact: Stéphane Oudard, MD, PhD    00 33 1 56 09 34 76    stephane.oudard@egp.aphp.fr   
Principal Investigator: Stéphane Oudard, MD, PhD         
Fôpital d'Instruction des Amées du Val de Grâce Recruiting
Paris, France, 75005
Contact: Sylvestre Le Moulec, MD       sylvestre.lemoulec@gmail.com   
Principal Investigator: Sylvestre Le Moulec, MD         
Hôpital Cochin Recruiting
Paris, France, 75014
Contact: Anatole Cessot, MD       anatole.cessot@cch.aphp.fr   
Principal Investigator: Anatole Cessot, MD         
Institut de Cancérologie Lucien Neuwirth Recruiting
Saint Priest en Jarez, France, 42270
Contact: Aline Guillot, MD    00 33 4 77 91 70 32    aline.guillot@icloire.com   
Principal Investigator: Aline Guillot, MD         
Centre Alexis Vautrin Recruiting
Vandoeuvre-lès-nancy, France, 54511
Contact: Lionnel Geoffrois, MD    00 33 3 83 59 84 61    l.geoffrois@nancy.unicancer.fr   
Principal Investigator: Lionnel Geoffrois, MD         
Institut Gustave Roussy Recruiting
Villejuif, France, 94805 cedex
Contact: Bernard Escudier, MD       bernard.escudier@igr.fr   
Principal Investigator: Bernard Escudier, MD         
Principal Investigator: Laurence Albiges, MD         
Sponsors and Collaborators
Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
Investigators
Principal Investigator: Stéphane Oudard, MD, PhD Hôpital Européen Georges Pompidou, Paris (France)
  More Information

No publications provided

Responsible Party: Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
ClinicalTrials.gov Identifier: NCT01715935     History of Changes
Other Study ID Numbers: 2011-000882-11
Study First Received: September 12, 2012
Last Updated: October 25, 2012
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Committee for the Protection of Personnes

Keywords provided by Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie:
Clear cells renal carcinoma
everolimus
neo-adjuvant treatment

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on September 14, 2014