Efficacy Study of Sunitinib and Everolimus (Rotational vs Sequential Arm) in Pats. With m Clear Cell Renal Cancer

NCT01784978 | Terminated Phase 2 DMC

• 1 other identifier: SUNRISES STUDY (CRAD001LIC34T)
• Study Type: interventional
• Target: 41
• Locations: 3 countries
• Sites: 10

Brief Summary

The objective of this study is to assess the progression-free survival, of patients who receive rotations of sunitinib and everolimus versus patients who receive sunitinib as a first line treatment followed by everolimus when progression occurs.

Conditions

Metastatic Renal Cell Carcinoma

Keywords

cancer; renal; metastatic; clear; cell; Sunitinib; Everolimus; Alternating

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) rate 1 year

  12 months

Secondary Outcomes (4)

• PFS of rotational arm versus PFS of the 2 lines in control arm

  From date of randomization until the date of first documented progression assesed up to 30 months

• Overall Survival

  From the date of the tratment start to the date of death or the last contact for alived patients at the momment of data censored. Assesed up to 30 months

• Safety Profile

  From the first treatment dose until 28 days after study treatment discontinuation. Assesed up to 30 months

• Objective tumor response rate per arm

  From the date of first tumor response to the date of progression or start date of other cancer therapy. Assesed up to 30 months

Study Arms (2)

Rotational arm

EXPERIMENTAL

Alternating cycles of treatment with sunitinib and everolimus; repeating cycles of 24 weeks of treatment consisting of 12 weeks of sunitinib 4weeks on 2 weeks off, 50 mg pd followed by 12 weeks of everolimus 10 mg per day 11 weeks on 1 week off in patients with metastatic clear cell renal cancer.

Drug: Sunitinib; Drug: Everolimus

Sequential arm

ACTIVE COMPARATOR

The comparative arm will be the standard regimen of sunitinib (50 mg pd 4/2) until progression, followed thereafter by everolimus (10 mg per day continuously, 11/1) until progression.

Drug: Sunitinib; Drug: Everolimus

Interventions

Sunitinib DRUG

50 mg pd

Also known as: SUTENT

Rotational arm; Sequential arm

Everolimus DRUG

10 mg pd

Also known as: AFINITOR

Rotational arm; Sequential arm

Eligibility Criteria

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

You may qualify if:

• Renal cell carcinoma with a predominant clear cell component confirmed by histology.
• Advanced disease: metastatic AND, not suitable for resection
• Male or female, aged 18 years or older
• ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 or 1
• Low or intermediate MSKCC (Memorial Sloan Kettering Cancer Center) prognostic risk score,i.e. no more than 2 of the following:
• Karnofsky performance status (\<80%)
• Low serum hemoglobin (≤ 13 g/dL for males and ≤ 11.5 g/dL for females)
• High corrected serum calcium (≥ 10 mg/dL)
• Target and/or non-target lesions according to RECIST 1.1 ( Response Evaluation Criteria in Solid Tumors)
• Expected survival of at least 3 months.
• No prior systemic treatment. But adjuvant treatment is ok if stopped from ≥ 24 months
• Adequate bone marrow function as shown by:
• Adequate liver function as shown by:
• Adequate renal function as shown by serum creatinine ≤ 1.5 x ULN (upper limit of normal)
• Left ventricular ejection fraction ≥55% on gated cardiac blood pool scan, or normal left ventricular function and fractional shortening on echocardiogram (according to institutional limits).

You may not qualify if:

• Prior treatment with VEGF-targeting agents or multi-kinase inhibitors or mTOR-targeting agents
• Active central nervous system metastases.
• Other malignancy diagnosed within the last 5 years, except the following if adequately treated: superficial squamous cell carcinoma or basal cell carcinoma of skin, superficial bladder cancer (T1 and G1 or T1 and G2), stage 1 cervical cancer.
• Treatment with an investigational agent in the last 4 w.
• Known to be HIV positive.
• Evidence of chronic hepatitis due to hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Clinically significant heart disease (NYHA Class III or IV)
• History of hypertension requiring hospitalization.
• Other serious illnesses,
• Immunotherapy or chemotherapy in the last 4 w (6 weeks for nitrosoureas)
• Major surgery in the last 4 w, or planned in the next 6 w
• Radiation therapy in the last 2 w, or planned in the next 6 w
• NCI CTCAE (Common Toxicity Criteria for Adverse Effects) version 4.0 grade 3 or worse hemorrhage in last 4 w.
• Any of the following in the last year: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.

Sponsors & Collaborators

• Associació per a la Recerca Oncologica, Spain: lead
• Novartis: collaborator
• Pivotal S.L.: collaborator

Study Sites (10)

Hopital Bordeaux University

Bordeaux, France

Location

ALEXANDRA General Hospital of Athens

Athens, 11528, Greece

Location

Hospital Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33006, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28026, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Clara Campal. Hospital Sanchinarro

Madrid, 28050, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Hospital General Universitario de Valencia

Valencia, Spain

Location

Related Publications (1)

• Rodriguez-Vida A, Bamias A, Esteban E, Saez MI, Lopez-Brea M, Castellano D, Caballero C, Gonzalez-Larriba JL, Calvo E, Macia S, Ravaud A, Bellmunt J. Randomised Phase II study comparing alternating cycles of sunitinib and everolimus vs standard sequential administration in first-line metastatic renal carcinoma (SUNRISES study). BJU Int. 2020 Nov;126(5):559-567. doi: 10.1111/bju.15165. Epub 2020 Aug 2.

  PMID: 32654362 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasms; Neoplasm Metastasis; Margins of Excision

Interventions

Sunitinib; Everolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; 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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Morphological and Microscopic Findings

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Joaquim Bellmunt, MD/PhD

  Associacio Per la Recerca Oncológica (APRO)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2012
• First Posted: February 6, 2013
• Study Start: February 12, 2013
• Primary Completion: May 8, 2017
• Study Completion: May 8, 2017
• Last Updated: October 2, 2017

Record last verified: 2017-09

Locations

GR (1); ES (8); FR (1)