Phase II Study of the Optimal Scheme of Administration of Pazopanib in Thyroid Carcinoma

Learn more about:
Related Clinical Trial
Optimising Molecular Radionuclide Therapy Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer Development of Liquid Biopsy Technologies for Noninvasive Cancer Diagnostics in Patients With Suspicious Thyroid Nodules or Thyroid Cancer Function Integrity of Neck Anatomy in Thyroid Surgery An Investigational Scan (hpMRI) for Monitoring Treatment Response in Patients With Thyroid Cancer Undergoing Radiation Therapy and/or Systemic Therapy Vemurafenib Plus Copanlisib in Radioiodine-Refractory (RAIR) Thyroid Cancers Malignancy Predictors, Bethesda and TI-RADS Scores Correlated With Final Histopathology in Thyroid Diseases Effect of Artificial Tears on Radioiodine Levels in the Nasolacrimal Duct System Evaluation of a New CZT System Thermal Ablation and Spine Stereotactic Radiosurgery in Treating Patients With Spine Metastases at Risk for Compressing the Spinal Cord Doxepin Hydrochloride in Treating Esophageal Pain in Patients With Thoracic Cancer Receiving Radiation Therapy to the Thorax With or Without Chemotherapy Cabozantinib S-Malate in Treating Younger Patients With Recurrent or Refractory Solid Tumors Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction Modified Cormack Lehane Scores Evaluated by Laryngoscopy During Awake Versus Under General Anesthesia Parathyroid Reimplantation in Forearm Subcutaneous Tissue During Thyroidectomy: a Simple Way to Avoid Ipoparathyroidism and Evaluate Graft Function Efficacy of Fibrin Sealant to Reduce the Amount of Post-thyroidectomy Drain A Study Into the Effect of Seprafilm in Open Total Thyroidectomy Lenvatinib and Pembrolizumab in DTC Study of XL184 (Cabozantinib) in Adults With Advanced Malignancies Genomic Profiling of Nodular Thyroid Disease and Thyroid Cancer Comparative Study of Robot BABA Approach and Chest Breast Approach for Lateral Neck Dissection Sunitinib Malate in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer Influence of Thyroid Hormones on the Woundhealing Process ctDNA in Patients With Thyroid Nodules Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine Aflibercept in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy Radioiodine Dosimetry Protocol for Thyroid Cancer Metastases Evaluation of Lancet Blood Sampling for Radioiodine Dosimetry in Thyroid Cancer Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer Clinical Evaluation of 18F-DOPA Positron Emission Tomography in Medullary Thyroid Cancer Biomarkers to Distinguish Benign From Malignant Thyroid Neoplasm Gallium-68 Prostate Specific Membrane Antigen PET in Diagnosing Patients With Thyroid Cancer Effect of Polyglycolic Acid Mesh (Neoveil) in Thyroid Cancer Surgery The Effect of Coffee on the Absorption of Thyroid Hormone in Patients With Thyroid Carcinoma Lesion Dosimetry With Iodine-124 in Metastatic Thyroid Carcinoma Renal Tracer Elimination in Thyroid Cancer Patients Treated With 131-Iodine Trial of LBH589 in Metastatic Thyroid Cancer Enhancing Radioiodine (RAI) Incorporation Into BRAF Mutant, RAI-Refractory Thyroid Cancers With the BRAF Inhibitor Vemurafenib: A Pilot Study Prospective, Non-interventional, Post-authorization Safety Study That Includes All Patients Diagnosed as Unresectable Differentiated Thyroid Carcinoma and Treated With Sorafenib Phase II Study of the Optimal Scheme of Administration of Pazopanib in Thyroid Carcinoma Study of Sulfatinib in Treating Advanced Medullary Thyroid Carcinoma and Iodine-refractory Differentiated Thyroid Carcinoma Thyroid Cancer and Sunitinib Feasibility of Endoscopic Thyroidectomy for Thyroid Carcinoma Sorafenib Phase II Study for Japanese Anaplastic or Medullary Thyroid Carcinoma Patients Lipid Metabolic Status in Thyroid Carcinoma

Brief Title

Phase II Study of the Optimal Scheme of Administration of Pazopanib in Thyroid Carcinoma

Official Title

A Randomized, Multicenter, Open-label, Phase II Study of the Optimal Scheme of Administration of Pazopanib in Thyroid Carcinoma

Brief Summary

      The objective of this study is to determine the feasibility of pazopanib treatment
      interruption with reintroduction at progression in iodine refractory progressive
      Differentiated Thyroid Cancer (DTC) patients as compared to pazopanib continuous
      administration.
    

Detailed Description

      Total or near-total thyroidectomy is the primary treatment for differentiated thyroid
      carcinoma. Postoperatively, DTC are treated with radioiodine (131I) and thyroid stimulating
      hormone (TSH) suppressive levothyroxine therapy.

      But 5% to 20% of patients with DTC develop distant metastases; some of them become refractory
      to 131I therapy.

      Targeted therapies have been studied in iodine refractory DTC for several years but none of
      these treatments has yet been approved in DTC and clinicians continue to enroll patients in
      clinical trials. The agents used so far in thyroid cancer are small molecules sharing the
      property to inhibit various tyrosine kinase receptors such as Vascular Endothelial Growth
      Factor Receptor (VEGFR), Epidermal Growth Factor Receptor (EGFR), RET or c-met.

      The VEGF (Vascular Endothelial Growth Factor) is one of the several pro angiogenic molecules
      that play a pivotal role in angiogenesis, one of the mechanisms involved in tumor growth and
      dissemination.

      VEGF expression is highly prevalent in Papillary Thyroid Carcinoma (PTCs) (79%), Follicular
      Thyroid Carcinoma (FTCs) (50%) or Poorly Differentiated Thyroid Carcinoma (PDTCs) (37%) and
      VEGFR is respectively expressed in 76%, 83% and 25% for VEGRF-1 and 68%, 56% and 37% for
      VEGRF-2.

      Pazopanib (GW786034 - GlaxoSmithKline) is an orally administered, potent multitarget tyrosine
      kinase inhibitor of VEGFR in particular (but also of PDGFR-α and -β, and stem cell factor
      receptor c-Kit).

      The results obtained in metastatic or locally advanced refractory DTC are currently available
      (phase II study of 39 patients with metastatic, rapidly progressive RAI-refractory DTC,
      treated with pazopanib 800mg daily, were published in Lancet Oncology in 2010 by KC Bible),
      demonstrating the efficacy of these therapies in this indication. However, no clear data is
      yet available indicating the optimal duration of treatment in first line therapy: patients
      are currently treated until progression or until drug discontinuation due to toxicity.
      Indeed, patients may have some difficulties to manage the chronic mild to moderate (grade
      1-2) side-effects related to long-term treatment, leading some asymptomatic patients in whom
      tumor is controlled by TKI treatment to ask for treatment interruption.

      The intermittent administration should avoid the occurrence of long-term adverse event and
      subsequent dose reductions or discontinuation, thus allowing a longer control of underlying
      disease.

      All these considerations led our reflexion in the design of the present study, that is to say
      to determine the feasibility of pazopanib treatment interruption with reintroduction at
      progression in iodine refractory progressive DTC patients as compared to pazopanib continuous
      administration, after 6 initial cycles of pazopanib 800 mg daily for all patients included in
      the study, with a strong rationale for intermittent administration of pazopanib.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Time to treatment failure (TTF)

Secondary Outcome

 Objective Response Rate (ORR)

Condition

Thyroid Carcinoma

Intervention

Continuous pazopanib (Arm A)

Study Arms / Comparison Groups

 Continuous pazopanib (Arm A)
Description:  Daily oral administration of pazopanib 800mg (28 days cycles) from randomization until progression (according to RECIST 1.1) under treatment, after an initial period of 6 cycles (28 days) of daily administration of pazopanib 800mg from inclusion until randomization

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

168

Start Date

March 2013

Completion Date

January 2019

Primary Completion Date

January 2019

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 18 years old,

          -  Histologically confirmed diagnosis of differentiated thyroid cancer (papillary,
             follicular and poorly differentiated)

          -  Archival tumor sample available. It will be provided for all subjects, for biomarker
             analysis before and/or during study treatment.

          -  Patients must have been treated with therapeutic RAI. Patients may have received prior
             treatment with either 1 line of chemotherapy and/or up to 1 Tyrosine Kinase Inhibitor,

          -  Resistance to therapeutic radioiodine (RAI) (for DTC) as demonstrated at least by one
             of the following:

               -  Absence of iodine uptake in at least one target lesion on a post-therapy
                  radioactive iodine scan,

               -  Presence of a target lesion after a cumulative radio-iodine activity of at least
                  600 mCi,

               -  Patient with uptake who have RAI treatment of at least 100 mCi within the last 12
                  months and have disease progression,

          -  Documented progression as per RECIST 1.1 based on 2 consecutives imaging performed
             within the last 12 months,

          -  Measurable disease according to RECIST version 1.1,

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1,

          -  Adequate organ system function defined as the following:

        Hematology:

          -  Absolute Neutrophils Count (ANC) ≥ 1.5 Gi/L

          -  Hemoglobin ≥ 9 g/dL (5.6µM) (transfusion is not allowed within 7 days of screening
             assessments)

          -  Platelets ≥ 100 Gi/L

          -  Prothrombin Time (PT) ≤ 1.2 x ULN or International Normalized Ratio (INR) ≤ 1.2
             Subjects receiving anticoagulant therapy are eligible if their INR is stable and
             within the recommended range for the desired target of anticoagulation

          -  Activated Partial Thromboplastin Time (aPTT) ≤ 1.2 x ULN

        Electrolytes :

        - Potassium within normal ranges.

        Hepatic :

          -  Total bilirubin ≤ 1.5 x ULN

          -  Alanine AminoTansferase (ALAT) and Aspartate AminoTransferase (ASAT) ≤ 2.5 x ULN
             Concomitant elevation in bilirubin and ASAT/ALAT above 1.0xULN is not allowed

        Renal :

          -  Serum creatinine ≤ 1.5 mg/dL (133µM) or if serum creatinine> 1.5 mg/dL, calculated
             creatinine clearance (ClCR) ≥ 50 mL/min (Cockcroft formula or MDRD formula for
             patients older than 65 years old)

          -  Urine Protein to Creatinine Ratio (UPC) < 1; If UPC ratio ≥ 1, then a 24-hour urine
             protein must be assessed. Subjects must have a 24-hour urine protein value < 1 gram to
             be eligible Use of urine dipstick for renal function assessment is not acceptable

               -  Women of childbearing potential must have a negative urine or serum pregnancy
                  test within 7 days of first dose of pazopanib. They must be willing to use
                  effective contraception methods during the study and up to 7 days after the last
                  pazopanib administration.

               -  Affiliated to the French social security system.

               -  Subjects must provide written informed consent prior to perform any
                  study-specific procedure or assessment and must be willing to comply with
                  treatment and follow up.

        Note: Procedures conducted as part of the subject's routine clinical management (e.g.,
        blood count, imaging study such as bone scan) and obtained prior to signing of informed
        consent may be utilized for screening or baseline purposes provided these procedures are
        conducted as specified in the protocol,

        Exclusion Criteria:

          -  Other histological sub-types of thyroid tumors like medullar carcinoma, anaplastic
             carcinoma, lymphoma or sarcoma,

          -  Prior treatment with pazopanib,

          -  Prior malignancy, Subjects who have had another malignancy and have been disease-free
             for 5 years, or subjects with a history of completely resected non-melanomatous skin
             carcinoma or successfully treated in situ carcinoma are eligible

          -  Symptomatic metastases of Central nervous system (CNS) requiring or having required
             steroids or enzyme-inducing anticonvulsants within 4 weeks before inclusion ,

          -  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 with risk of bleeding,

               -  Inflammatory bowel disease (e.g. ulcerative colitis, Crohn'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 begin study treatment,

          -  Clinically significant gastrointestinal abnormalities that may affect absorption of
             investigational product including, but not limited to:

               -  Malabsorption syndrome,

               -  Major resection of the stomach or small bowel,

          -  Corrected QT interval (QTc) > 480 msec (correction method according to the Bazett's
             method),

          -  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),

               -  Cerebrovascular accident including Transient Ischemic Attack (TIA), pulmonary
                  embolism or untreated Deep Venous Thrombosis (DVT), Subjects with recent DVT who
                  have been treated with therapeutic anti-coagulating agents for at least 6 weeks
                  are eligible,

          -  Poorly controlled hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood
             pressure ≥ 90 mmHg) as described in the section 7.2 "Study requirements" of this
             protocol, Initiation or adjustment of antihypertensive medication(s) is permitted
             prior to study entry. At least one day after antihypertensive medication initiation or
             adjustment, blood pressure (BP) must be re-assessed three times at approximately
             2-minute intervals. 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 mmHg (OR 150/90 mm Hg, if this criterion is approved by the coordination
             center) in order to be eligible.

          -  Major surgery or trauma within 28 days prior to first dose of investigational product
             and/or presence of any non-healing wound, fracture, or ulcer (procedures such as
             catheter placement are 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, Lesions infiltrating major pulmonary
             vessels (contiguous tumor 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.

          -  Hemoptysis within the last 8 weeks before inclusion,

          -  Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drug,

          -  Treatment with any of the following anti-cancer therapies :

               -  radiation therapy, surgery or tumor embolization within 14 days prior to the
                  first dose of pazopanib (analgesic radiation therapy is allowed if the radiation
                  field doesn't include a potential target lesion for tumor assessments),

               -  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,

          -  Administration of other oncologic drug or any non-oncologic investigational drug
             within 30 days (or 5 half lives whichever is longer) prior to receiving the first dose
             of study treatment, or planned to be administered during the study participation,

          -  Unable or unwilling to discontinue use of prohibited medications listed in Section
             6.2.4.c "Prohibited medications" for at least 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 (according to the NCI-CTC AE v4.0), except alopecia,

          -  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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Christelle De La Fouchardière, MD, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT01813136

Organization ID

PAZOTHYR

Secondary IDs

2012-003162-41

Responsible Party

Sponsor

Study Sponsor

Centre Leon Berard

Collaborators

 GlaxoSmithKline

Study Sponsor

Christelle De La Fouchardière, MD, Principal Investigator, Centre Léon Bérard; Lyon


Verification Date

August 2019