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Multicenter Dose-escalation Study of a Combination of Pazopanib and Bevacizumab in Patients With Metastatic Renal Cell Carcinoma or Others Advanced Solid Tumors (PARASOL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01202032
Recruitment Status : Completed
First Posted : September 15, 2010
Last Update Posted : May 18, 2016
Information provided by (Responsible Party):
Centre Leon Berard

Brief Summary:

This is an open-label, multicenter dose-escalation phase I study using a 3+3+3 design (i.e., 3 to 9 patients per dose level) in patients with mRCC or others advanced refractory solid tumors. Enrolment will be performed to include approximately ½ of patients with mRCC.

The primary endpoint is the occurrence of limiting toxicities leading to definitive discontinuation of the study drugs during the first 24 weeks in absence of progression of the disease.

Secondary endpoints included the occurrence of Dose Limiting Toxicities (DLTs) evaluated during the first two cycles; overall response rate, 6-months progression-free survival rate and Pharmacokinetic assessments.

Condition or disease Intervention/treatment Phase
Metastatic Renal Cell Carcinoma Advanced Refractory Solid Tumors Histologically or Cytologically Confirmed Drug: Association of Bevacizumab (BVC)+ Pazopanib (PZP) Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bevacizumab in Patients With Metastatic Renal Cell Carcinoma or Others Advanced Solid Tumors
Study Start Date : July 2010
Actual Primary Completion Date : January 2013
Actual Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

Intervention Details:
  • Drug: Association of Bevacizumab (BVC)+ Pazopanib (PZP)

    Treatment is administered in 28-day cycles, during which patients received BVC intravenously every 2 weeks and oral PZP once daily from days 1 to 28. For the first cycle, PZP is administered alone from days 1 to 14.

    The starting dose for dose escalation is BVC at 7.5 mg/kg in combination with PZP 400 mg (level 1).

    The therapy regimens for each dose level are respectively:

    BVC 7.5 mg/kg + PZP 600 mg (level 2) BVC 10 mg/kg + PZP 600 mg (level 3) BVC 10 mg/kg + PZP 800 mg (level 4). Patients who experience grades 3 to 4 adverse events have dose adjustments to one or both drugs. Dose reductions affect in priority the administration of PZP. Doses reductions to PZP are made in 200-mg decrements and to BVC to 2.5-mg/kg decrements.

    Patients with toxicities that warrant reductions at either PZP 400 mg or BVC 7.5 mg/kg are withdrawn from the study.

Primary Outcome Measures :
  1. Determination of the Optimal Long Exposure Dose (OLED) [ Time Frame: 24 weeks for each patient ]
    The primary endpoint is the occurrence of an interruption of one drug of the association of a duration superior to 4 weeks during the first 24 weeks in absence of progression of the disease.

Secondary Outcome Measures :
  1. The determination of the maximum-tolerated dose (MTD) [ Time Frame: 8 weeks for each patient ]
  2. To estimate the overall response rate (ORR) [ Time Frame: 24 weeks ]
  3. To estimate the 6-month progression-free survival (PFS) rate [ Time Frame: 24 weeks ]
  4. To characterize the pharmacokinetic (PK) profile of Pazopanib when combined with Bevacizumab. [ Time Frame: 8 weeks ]

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Age >18 years.
  • Dated and signed written informed consent.
  • Histologically progressive mRCC or other advanced refractory histologically or cytologically confirmed solid tumors. In mRCC situation, only patients who have received no prior therapy or who have failed only one prior systemic therapy (except tyrosine kinase inhibitors) are allowed; for patients with other advanced refractory solid tumors, no more than three prior systemic therapy regimens (except tyrosine kinase inhibitors) are permitted.
  • ECOG performance status of 0 or 1.
  • At least one measurable site of disease as defined by RECIST criteria 1.1. based on investigator's assessment.
  • Adequate bone marrow function: absolute neutrophil count >=1.5 x 109/L, platelet count >= 100 x 109/L, and hemoglobin >= 9 g/dL.
  • Adequate liver function: AST/ALT <= 2 x upper limit of normal (ULN) and total bilirubin in the normal values.
  • Adequate coagulation function: prothrombin time (PT) or international normalized ratio (INR) <=1.2 x ULN and activated partial thromboplastin time (APTT)<=1.2x ULN.
  • Adequate renal function: serum creatinine ≤ 1.5 mg/dL (133 µmol/L) or, if greater than 1.5 mg/dL: calculated creatinine clearance ≥ 50 mL/min.
  • Absence of proteinuria confirmed by urinary dipstick test. If the dipstick test is twice positive, proteinuria will be quantified on a complete 24h urine sample: urine protein value must be <1 g /L.
  • Ability to swallow and retain oral medication.
  • Adequate contraception methods.
  • Mandatory affiliation with a health insurance company.

Exclusion Criteria:

  • Prior Pazopanib treatment.
  • Prior Bevacizumab treatment within 6 months prior to begin study treatment. Patients with any grade 3 or grade 4 toxicity during prior BVC therapy are not eligible.
  • Prior treatment with any tyrosine kinase inhibitor.
  • Concomitant participation to an other clinical study estimating a experimental agent.
  • Patients with any haematological, renal, or neurological grade 3-4 toxicity during prior systemic therapy regimens.
  • Patients with any liver injury grade 3-4 during prior systemic therapy regimens.
  • Patients with squamous non-small cell lung carcinoma.
  • Patients with high vascular and nephrologic risks [uncontrolled hypertension while receiving appropriate medication (SBP ≥ 150 mmHg and DBP ≥ 90 mmHg), significant proteinuria, low creatinine clearance level…].
  • Patients with brain metastases.
  • Clinically significant gastrointestinal abnormalities which might interfere with oral dosing:

Active peptic ulcer disease;kown intraluminal metastatic lesion/s with suspected bleeding;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; malabsorption syndrome; major resection of the stomach or small bowel.

  • History of Gilbert's disease.
  • Patients with chronic hepatitis.
  • Any unstable or serious concurrent condition (i.e., presence of uncontrolled infection).
  • Prolongation of corrected QT interval (QTc) >480 msecs using Bazett's formula.
  • History of any one of more of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting; myocardial infarction; unstable angina; symptomatic peripheral vascular disease; coronary artery by-pass graft surgery; class III or IV congestive heart failure as defined by the New York Heart Association (NYHA); history of cerebrovascular accident, 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-coagulant agents (excluding therapeutic warfarin) for at least 6 weeks are eligible.

  • Hemoptysis within 6 weeks of first dose of study drug.
  • Evidence of active bleeding or bleeding diathesis.
  • Anticoagulant treatment with curative intent.
  • Known endobronchial lesions or involvement of large pulmonary vessels by tumor.
  • 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.
  • Radiation therapy, surgery or tumor embolization within 2 weeks prior to the first dose of study drug.
  • Chemotherapy, immunotherapy, biological therapy, hormonal therapy or treatment with an investigational agent within 14 days or 5 half-lives, whichever is longer prior to the first dose of study drug.
  • Patient unable or unwilling to discontinue predefined prohibited medications listed in the protocol for 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.
  • Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to PZP.
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  • Clinically assessed as having inadequate venous access for PK sampling.
  • Women who are pregnant or breast feeding.

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 identifier (NCT number): NCT01202032

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Centre Léon BERARD
Lyon, France, 69373
Sponsors and Collaborators
Centre Leon Berard
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Principal Investigator: SYLVIE NEGRIER, Phd Centre Léon Bérard; Lyon; FRANCE

Additional Information:

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Centre Leon Berard Identifier: NCT01202032     History of Changes
Other Study ID Numbers: PARASOL
First Posted: September 15, 2010    Key Record Dates
Last Update Posted: May 18, 2016
Last Verified: May 2016

Keywords provided by Centre Leon Berard:
Metastatic renal cell carcinoma
Advanced solid tumors
Dose escalation
Association Pazopanib-Bevacizumab

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