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

NCT02446795 | Unknown Phase 1

• 2 other identifiers: QUASAR - 2014-0012015-000194-12
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 5

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.

Conditions

Renal Cell Carcinoma; Kidney Cancer

Keywords

Renal cell carcinoma; Isoquercetin; kidney cancer; sunitinib; fatigue

Outcome Measures

Primary Outcomes (2)

• Change of activity of isoquercetin as an anti-fatigue agent (FACT-F questionnaire)

  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.

  At baseline, and at day 70

• The maximum tolerated dose of isoquercetin administered concomitantly with sunitinib

  • 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;

  From baseline to Day 70

Secondary Outcomes (7)

• Effect of isoquercetin on quality of life (FACT-G score)

  Up to 12 months

• Effect of isoquercetin on serum markers of inflammation (C reactive protein, IL-6, IL10)

  Up to 12 months

• Effect of isoquercetin on dose density and patient compliance, as determined by dose reductions of sunitinib and requirements of schedule modification

  Up to 12 months

• Safety and tolerability: To evaluate the safety and tolerability (including AEs, SAEs, withdrawal of treatment due to AE, vital signs, ECG and clinical laboratory)

  Up to 12 months

• Effect of isoquercetin on muscle index (CT scans)

  Up to 12 months

Study Arms (2)

Experimental Arm

EXPERIMENTAL

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; Drug: Isoquercetin

Placebo Arm

PLACEBO COMPARATOR

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; Drug: Placebo

Interventions

Sunitinib DRUG

Sunitinib: 50mg once daily orally for 4 weeks followed by 2 weeks off treatment (either at 8 a.m. or at 8 p.m.)

Also known as: Background therapy

Experimental Arm; Placebo Arm

Isoquercetin DRUG

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).

Also known as: PR1

Experimental Arm

Placebo DRUG

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).

Also known as: PL1

Placebo Arm

Eligibility Criteria

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

You may qualify if:

• 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.
• 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;
• 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;
• ECOG PS of 0 or 1;
• Age ≥18 years;
• A female is eligible to enter and participate in this study if she is non-childbearing potential or agrees to use adequate contraception;
• Adequate organ system functions;
• Total serum calcium concentration \<12.0mg/dL;
• 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;
• Patient is able to swallow and retain oral tablets;
• Written informed consent obtained before any screening procedure and according to local guidelines.

You may not qualify if:

• History of another malignancy;
• History or clinical evidence of central nervous system (CNS) metastases
• Any clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding or affect absorption of investigational product
• Unable to tolerate continuous daily administration of 50 mg sunitinib
• Presence of uncontrolled infection;
• Serum potassium \< lower normal limits;
• Corrected QT interval (QTc) \>480 ms using Bazett's formula;
• History of cardiovascular conditions within the past 6 months:
• Poorly controlled hypertension (defined as systolic blood pressure (SBP) of \> 150mmHg or diastolic blood pressure (DBP) of \> 90mmHg) at baseline
• History of cerebrovascular accident (CVA) including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months;
• 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).
• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels;
• Evidence of active bleeding or bleeding diathesis;
• Significant hemoptysis within 6 weeks prior to first dose of study drug;
• 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;

Sponsors & Collaborators

• Consorzio Oncotech: lead
• Clinical Research Technology S.r.l.: collaborator
• Quercegen Pharmaceuticals: collaborator

Study Sites (5)

Azienda Ospedaliera Cardarelli Divisione Di Oncologia

Napoli, Napoli, 80131, Italy

NOT YET RECRUITING

Ospedale Oncologico Regionale - Centro di Riferimento Oncologico di Basilicata U.O. di Oncologia Medica

Rionero in Vulture, Potenza, 85028, Italy

NOT YET RECRUITING

Fondazione G. Pascale

Naples, Italy

NOT YET RECRUITING

University Federico II of Naples

Naples, Italy

RECRUITING

Azienda Ospedaliera Ruggi Aragona

Salerno, Italy

NOT YET RECRUITING

Related Publications (3)

• Aparicio LM, Pulido EG, Gallego GA. Sunitinib-induced asthenia: from molecular basis to clinical relief. Cancer Biol Ther. 2011 Nov 1;12(9):765-71. doi: 10.4161/cbt.12.9.18138.

  PMID: 22045104 RESULT

• Di Lorenzo G, Porta C, Bellmunt J, Sternberg C, Kirkali Z, Staehler M, Joniau S, Montorsi F, Buonerba C. Toxicities of targeted therapy and their management in kidney cancer. Eur Urol. 2011 Apr;59(4):526-40. doi: 10.1016/j.eururo.2011.01.002. Epub 2011 Jan 14.

  PMID: 21277078 RESULT

• Russo GL, Russo M, Ungaro P. AMP-activated protein kinase: a target for old drugs against diabetes and cancer. Biochem Pharmacol. 2013 Aug 1;86(3):339-50. doi: 10.1016/j.bcp.2013.05.023. Epub 2013 Jun 6.

  PMID: 23747347 RESULT

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms; Fatigue

Interventions

Sunitinib; isoquercitrin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; 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; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Giuseppe Di Lorenzo, MD

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giuseppe Di Lorenzo, MD

CONTACT

00390817467250; giuseppedilorenzoncol@hotmail.com

Carlo Buonerba, MD

CONTACT

00393934364015; carbuone@homail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2015
• First Posted: May 18, 2015
• Study Start: November 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: January 18, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (5)