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Metastatic Renal Cell CarcinomaPhase 2PIPELINENCT04462445

Prospective Translational Study Investigating Possible Molecular prEdictors of Resistance to First-Line pazopanIb

A Phase 2 study testing Pazopanib in people with Metastatic Renal Cell Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a prospective, single-arm, monocentric translational study designed to evaluate possible biomarkers of resistance to the first line of therapy with pazopanib in patients with metastatic renal cell carcinoma (mRCC) who have not received systemic therapy in both the adjuvant and metastatic phases. Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Metastatic Renal Cell Carcinoma
What is being tested?
Pazopanib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
No sites listed yet
Study dates
25 Jun 2015to 8 Feb 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed Informed Consent Form
  • Unresectable advanced or metastatic renal cell carcinoma (RCC) with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic agent, including treatment in the adjuvant setting
  • Availability of a representative formalin-fixed paraffin-embedded fractional Fokker-Planck equation (FFPE) tumor specimen collected within 24 months of starting first-line pazopanib that enables the definitive diagnosis of renal cell carcinoma (RCC) (the archival specimen must contain adequate viable tumor tissue to enable candidate biomarkers status; the specimen may consist of a tissue block or at least 15 unstained serial sections; for core needle biopsy specimens at least two cores should be available for evaluation)
  • Measurable disease as defined by RECIST v1.1
  • Age ≥18 years
  • Hematology Absolute neutrophil count (ANC)≥1.5 X 109/L Hemoglobin ≥9 g/dL (5.6 mmol/L) Platelets ≥100 X 109/L Prothrombin time (PT) or international normalized ratio (INR)b ≤1.5 X upper limit of normal (ULN) Activated partial thromboplastin time (aPTT) ≤1.5 X upper limit of normal (ULN) Hepatic Total bilirubin ≤1.5 X upper limit of normal (ULN) Alanine amino transferase (ALT) and Aspartate aminotransferase (AST)c 2.5 X upper limit of normal (ULN) Patients with documented liver metastases <5 X upper limit of normal (ULN) Renal Serum creatinine 1.5 mg/dL (133 µmol/L) Or, if >1.5 mg/dL: Calculated creatinine clearance (ClCR) (reference appropriate appendix) ≥30 mL/min to ≥ 50 mL/min Urine Protein to Creatinine Ratio (UPC; appropriate appendix)<1 Or, 24-hour urine protein <1g
  • Eastern Cooperative Oncology Group (ECOG) performance Status 0-1

Who cannot join

  • Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: active peptic ulcer disease, known intraluminal metastatic lesion/s with risk of bleeding, inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease), 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.
  • History of any one or more of the following cardiovascular conditions within the past 6 months:
  • cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) - Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 millimetre (s) of mercury (mmHg) or diastolic blood pressure (DBP) of ≥ 90 millimetre (s) of mercury (mmHg)].
  • Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement. These three values should be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure. The mean SBP / DBP ratio must be <140/90 millimetre (s) of mercury (mmHg) (OR 150/90 millimetre (s) of mercury (mm Hg), if this criterion is approved by Safety Review Team) in order for a subject to be eligible for the study
  • History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
  • Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
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  • Major surgery or trauma within 28 days prior to first dose of pazopanib and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
  • Evidence of active bleeding or bleeding diathesis.
  • Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage Note: Lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions).
  • Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed.
  • Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed.
  • Recent hemoptysis (½ teaspoon of red blood within 8 weeks before first dose of study drug).
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
  • Treatment with any of the following anti-cancer therapies:
  • chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of Pazopanib

About this study

Official title: Prospective Translational Study Investigating Possible Molecular prEdictors of Resistance to First-Line pazopanIb in Metastatic reNal Cell Carcinoma

This is a prospective, single-arm, monocentric translational study designed to evaluate possible biomarkers of resistance to the first line of therapy with pazopanib in patients with metastatic renal cell carcinoma (mRCC) who have not received systemic therapy in both the adjuvant and metastatic phases.

Read the detailed description

a prospective, single-arm, monocentric translational study

Being tested
Pazopanib
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PazopanibDrug

Study groups in NCT04462445
Study groupRoleWhat they receive
pazopanibExperimentalPazopanib 800 mg (2x400mg ) taken orally daily as per clinical practice
Receives: Drug: Pazopanib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. A panel of possible predictive candidate biomarkers of resistance to anti-angiogenic targeted tyrosine kinase inhibitor (TKI)

    using next-generation sequencing (NGS) methods for future research. This will be done by within-patient comparison of metastatic tissue samples taken on commencement of first-line pazopanib, and secondly on development of TKI resistance

    Measured: 18 months

  2. The Overall Response Rate (ORR)

    evaluate per RECIST v.1.1 criteria in mRCC patients treated with first-line pazopanib in order to either correlate circulating angiogenic factors (CAFs) levels and gene candidate biomarkers status to clinical outcome when resistance develops

    Measured: 18 months

Secondary outcomes (4)

  1. Identification of other protein markers circulating in blood,

    To obtain serial blood samples from patients whilst they are being treated with pazopanib

    Measured: 18 months

  2. compare the frequency of previously defined promising circulating predictive biomarkers for pazopanib treatment

    between blood samples taken at commencement of therapy (baseline) and at the time of progressive disease (PD) as per RECIST 1.1 criteria as well as changes of interleukin 8 (IL-8), c-Met and hematopoietic growth factor (HGF) expression between metastatic tumour tissue samples in order to better understand changes in the tumor and in the levels of circulating angiogenic factors as resistance develops.

    Measured: 18 months

  3. Collect Data

    prospective and retrospective demographic, clinical and pathological data on patients who enter the study, enabling current and future correlation of biomarkers to clinical outcomes

    Measured: 18 months

  4. Perform subgroup analyses

    comparing the tissue and blood biomarkers identified in patients who developed secondary resistance with those biomarkers identified in patients who have primary resistance.

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2020
  2. Study start25 Jun 2015
  3. Primary completion8 Feb 2017
  4. Study completion8 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04462445
Sponsor's protocol ID
INT 146-14
Acronym
PIPELINE
Status last verified
Jun 2020
First submitted
2 Jul 2020
Last updated
10 Jul 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29. doi: 10.3322/caac.21208. Epub 2014 Jan 7.

    PubMed 24399786

  • Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med. 1996 Sep 19;335(12):865-75. doi: 10.1056/NEJM199609193351207. No abstract available.

    PubMed 8778606

  • Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993 May 28;260(5112):1317-20. doi: 10.1126/science.8493574.

    PubMed 8493574

  • George DJ, Kaelin WG Jr. The von Hippel-Lindau protein, vascular endothelial growth factor, and kidney cancer. N Engl J Med. 2003 Jul 31;349(5):419-21. doi: 10.1056/NEJMp030061. No abstract available.

    PubMed 12890838

  • Schwandt A, Wood LS, Rini B, Dreicer R. Management of side effects associated with sunitinib therapy for patients with renal cell carcinoma. Onco Targets Ther. 2009 Feb 18;2:51-61. doi: 10.2147/ott.s4052.

    PubMed 20616894

  • Sonpavde G, Hutson TE, Sternberg CN. Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma. Expert Opin Investig Drugs. 2008 Feb;17(2):253-61. doi: 10.1517/13543784.17.2.253.

    PubMed 18230058

  • Kumar R, Crouthamel MC, Rominger DH, Gontarek RR, Tummino PJ, Levin RA, King AG. Myelosuppression and kinase selectivity of multikinase angiogenesis inhibitors. Br J Cancer. 2009 Nov 17;101(10):1717-23. doi: 10.1038/sj.bjc.6605366. Epub 2009 Oct 20.

    PubMed 19844230

  • Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarba JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010 Feb 20;28(6):1061-8. doi: 10.1200/JCO.2009.23.9764. Epub 2010 Jan 25.

    PubMed 20100962

  • Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. doi: 10.1056/NEJMoa1303989.

    PubMed 23964934

  • Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, Gschwend JE, De Giorgi U, Parikh O, Hawkins R, Sevin E, Negrier S, Khan S, Diaz J, Redhu S, Mehmud F, Cella D. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol. 2014 May 10;32(14):1412-8. doi: 10.1200/JCO.2013.50.8267. Epub 2014 Mar 31.

    PubMed 24687826

  • Ravaud A, Gross-Goupil M. Overcoming resistance to tyrosine kinase inhibitors in renal cell carcinoma. Cancer Treat Rev. 2012 Dec;38(8):996-1003. doi: 10.1016/j.ctrv.2012.01.003. Epub 2012 Feb 12.

    PubMed 22330762

  • Hutson TE. Targeted therapies for the treatment of metastatic renal cell carcinoma: clinical evidence. Oncologist. 2011;16 Suppl 2(Suppl 2):14-22. doi: 10.1634/theoncologist.2011-S2-14.

    PubMed 21346036

  • Hernandez-Yanez M, Heymach JV, Zurita AJ. Circulating biomarkers in advanced renal cell carcinoma: clinical applications. Curr Oncol Rep. 2012 Jun;14(3):221-9. doi: 10.1007/s11912-012-0231-2.

    PubMed 22434312

  • Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer. 2008 Aug;8(8):592-603. doi: 10.1038/nrc2442.

    PubMed 18650835

  • Shojaei F, Lee JH, Simmons BH, Wong A, Esparza CO, Plumlee PA, Feng J, Stewart AE, Hu-Lowe DD, Christensen JG. HGF/c-Met acts as an alternative angiogenic pathway in sunitinib-resistant tumors. Cancer Res. 2010 Dec 15;70(24):10090-100. doi: 10.1158/0008-5472.CAN-10-0489. Epub 2010 Oct 15.

    PubMed 20952508

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pazopanib in people with Metastatic Renal Cell Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

A panel of possible predictive candidate biomarkers of resistance to anti-angiogenic targeted tyrosine kinase inhibitor (TKI) (time frame: 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04462445, which also lists 26 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2020; AzTrials last refreshed its copy on 6 Nov 2026.

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