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Isoquercetin as an Adjunct Therapy in Patients With Kidney Cancer Receiving First-line Sunitinib: a Phase I/II Trial (QUASAR)

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ClinicalTrials.gov Identifier: NCT02446795
Recruitment Status : Recruiting
First Posted : May 18, 2015
Last Update Posted : January 18, 2017
Sponsor:
Collaborators:
Clinical Research Technology S.r.l.
Quercegen Pharmaceuticals
Information provided by (Responsible Party):
Consorzio Oncotech

Brief Summary:
Advanced renal cell carcinoma is invariably fatal, with a life expectancy of 2-3 years since diagnosis. Sunitinib is the standard first-line treatment for this condition, but it is associated to multiple side effects, with fatigue being reported in 51-63% of patients. As sunitinib-induced fatigue is likely to be mediated by inhibition of AMPk function, the investigators hypothesize that isoquercetin, which is hydrolyzed in vivo to quercetin, a known AMPk activator, is able to reduce fatigue in kidney cancer patients taking sunitinib.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Kidney Cancer Drug: Sunitinib Drug: Isoquercetin Drug: Placebo Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Isoquercetin as an Adjunct Therapy in Patients With Kidney Cancer Receiving First-line Sunitinib: a Phase I/II Trial
Study Start Date : November 2016
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Cancer

Arm Intervention/treatment
Experimental: Experimental Arm
Phase I Sunitinib: 50mg once daily orally schedule treatment according to Investigator's choice Isoquercetin: 225mg twice a day (at 08 a.m. and at 4 p.m). Phase II Sunitinib: 50mg once daily orally schedule treatment according to Investigator's choice Isoquercetin: 450 mg twice a day (at 08 a.m. and at 4 p.m).
Drug: Sunitinib
Sunitinib: 50mg once daily orally for 4 weeks followed by 2 weeks off treatment (either at 8 a.m. or at 8 p.m.)
Other Name: Background therapy

Drug: Isoquercetin
Isoquercetin: 225mg twice a day(at 08 a.m. and at 4 p.m)/Isoquercetin: 450 mg twice a day(at 08 a.m. and at 4 p.m).
Other Name: PR1

Placebo Comparator: Placebo Arm
Phase I Sunitinib: 50mg once daily orally schedule treatment according to Investigator's choice Placebo: 225mg twice a day (at 08 a.m. and at 4 p.m). Phase II Sunitinib: 50mg once daily orally schedule treatment according to Investigator's choice Placebo: 450 mg twice a day (at 08 a.m. and at 4 p.m).
Drug: Sunitinib
Sunitinib: 50mg once daily orally for 4 weeks followed by 2 weeks off treatment (either at 8 a.m. or at 8 p.m.)
Other Name: Background therapy

Drug: Placebo
Placebo: 225mg twice a day(at 08 a.m. and at 4 p.m)/Placebo: 450 mg twice a day(at 08 a.m. and at 4 p.m).
Other Name: PL1




Primary Outcome Measures :
  1. Change of activity of isoquercetin as an anti-fatigue agent (FACT-F questionnaire) [ Time Frame: At baseline, and at day 70 ]
    To evaluate the activity of isoquercetin as an anti-fatigue agent in patients with kidney cancer receiving sunitinib by using the FACT-F questionnaire after 2 sunitinib cycles.

  2. The maximum tolerated dose of isoquercetin administered concomitantly with sunitinib [ Time Frame: From baseline to Day 70 ]
    • The maximum tolerated dose (450/900 mg daily) of isoquercetin administered concomitantly with sunitinib is the primary end point of the phase I part of the trial;


Secondary Outcome Measures :
  1. Effect of isoquercetin on quality of life (FACT-G score) [ Time Frame: Up to 12 months ]
    To evaluate the effect of isoquercetin on quality of life as assessed by the FACT-G score

  2. Effect of isoquercetin on serum markers of inflammation (C reactive protein, IL-6, IL10) [ Time Frame: Up to 12 months ]
    To evaluate the effect of isoquercetin on serum markers of inflammation (C reactive protein, IL-6, IL10)

  3. Effect of isoquercetin on dose density and patient compliance, as determined by dose reductions of sunitinib and requirements of schedule modification [ Time Frame: Up to 12 months ]
    To evaluate the effect of isoquercetin on dose density and patient compliance

  4. Safety and tolerability: To evaluate the safety and tolerability (including AEs, SAEs, withdrawal of treatment due to AE, vital signs, ECG and clinical laboratory) [ Time Frame: Up to 12 months ]
  5. Effect of isoquercetin on muscle index (CT scans) [ Time Frame: Up to 12 months ]
    To evaluate the effect of isoquercetin on muscle index using CT scans

  6. Incidence of deep venous thrombosis (doppler ultrasound) [ Time Frame: Up to 12 months ]
    Incidence of deep venous thrombosis, as assessed by doppler ultrasound

  7. Effect of isoquercetin on patient compliance (questionnaire) [ Time Frame: Up to 12 months ]
    To evaluate the effect of isoquercetin on patient compliance will be used a questionnaire



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have received no prior systemic therapy other than sunitinib (including interleukin-2, interferon-α, chemotherapy, bevacizumab, mTOR inhibitor sorafenib or other VEGF TKI) for advanced or metastatic RCC. Patients who received adjuvant treatment with a cancer vaccine are eligible.
  2. Patients with locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic renal cell carcinoma of any histology (equivalent to Stage IV RCC according to AJCC staging) for whom treatment with sunitinib is either planned or ongoing. Patients with non-measurable disease are allowed if metastatic disease can be confirmed;
  3. Patients for whom treatment with sunitinib is planned must have had a whole body CT scan within 30 days prior to enrollment; patients who are already being treated with sunitinib at the time of enrollment must have had a whole body CT scan showing non progressive disease according to the RECIST criteria within 30 days of enrollment;
  4. ECOG PS of 0 or 1;
  5. Age ≥18 years;
  6. A female is eligible to enter and participate in this study if she is non-childbearing potential or agrees to use adequate contraception;
  7. Adequate organ system functions;
  8. Total serum calcium concentration <12.0mg/dL;
  9. Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN) as assessed by echocardiography (ECHO) or multigated acquisition (MUGA) scan. The same modality used at baseline must be applied for subsequent evaluations;
  10. Patient is able to swallow and retain oral tablets;
  11. Written informed consent obtained before any screening procedure and according to local guidelines.

Exclusion Criteria:

  1. History of another malignancy;
  2. History or clinical evidence of central nervous system (CNS) metastases
  3. Any clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding or affect absorption of investigational product
  4. Unable to tolerate continuous daily administration of 50 mg sunitinib
  5. Presence of uncontrolled infection;
  6. Serum potassium < lower normal limits;
  7. Corrected QT interval (QTc) >480 ms using Bazett's formula;
  8. History of cardiovascular conditions within the past 6 months:
  9. Poorly controlled hypertension (defined as systolic blood pressure (SBP) of > 150mmHg or diastolic blood pressure (DBP) of > 90mmHg) at baseline
  10. History of cerebrovascular accident (CVA) including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months;
  11. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).
  12. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels;
  13. Evidence of active bleeding or bleeding diathesis;
  14. Significant hemoptysis within 6 weeks prior to first dose of study drug;
  15. Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study;
  16. Use any prohibited medications within 14 days of the first dose of study medication;
  17. Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug;
  18. Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of study treatment;
  19. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to or sunitinib;
  20. Pregnant or lactating female patients who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug;
  21. Clinically significant depression (PHQ-9 score >15), anxiety (GAD score >10), clinically significant insomnia (positivity of ISQ).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02446795


Contacts
Contact: Giuseppe Di Lorenzo, MD 00390817467250 giuseppedilorenzoncol@hotmail.com
Contact: Carlo Buonerba, MD 00393934364015 carbuone@homail.com

Locations
Italy
Ospedale Oncologico Regionale - Centro di Riferimento Oncologico di Basilicata U.O. di Oncologia Medica Not yet recruiting
Rionero in vulture, Potenza, Italy, 85028
Principal Investigator: Michele Aieta, MD         
Fondazione G. Pascale Not yet recruiting
Naples, Italy
Contact: Sandro Pignata         
Principal Investigator: Sandro Pignata         
University Federico II of Naples Recruiting
Naples, Italy
Contact: Giuseppe Di Lorenzo, MD       giuseppedilorenzoncol@hotmail.com   
Principal Investigator: Giuseppe Di Lorenzo         
Azienda Ospedaliera Cardarelli Divisione Di Oncologia Not yet recruiting
Napoli, Italy, 80131
Principal Investigator: GIACOMO CARTENÌ, Md         
Azienda Ospedaliera Ruggi Aragona Not yet recruiting
Salerno, Italy
Contact: Stefano Pepe         
Principal Investigator: Stefano Pepe         
Sponsors and Collaborators
Consorzio Oncotech
Clinical Research Technology S.r.l.
Quercegen Pharmaceuticals
Investigators
Principal Investigator: Giuseppe Di Lorenzo, MD

Publications of Results:
Responsible Party: Consorzio Oncotech
ClinicalTrials.gov Identifier: NCT02446795     History of Changes
Other Study ID Numbers: QUASAR - 2014-001
2015-000194-12 ( EudraCT Number )
First Posted: May 18, 2015    Key Record Dates
Last Update Posted: January 18, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Consorzio Oncotech:
Renal cell carcinoma
Isoquercetin
kidney cancer
sunitinib
fatigue

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sunitinib
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors