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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01813136
• Date of registration: 11/03/2013
• Prospective Registration: No
• Primary sponsor: Centre Leon Berard
• Public title: Phase II Study of the Optimal Scheme of Administration of Pazopanib in Thyroid Carcinoma
• Scientific title: A Randomized, Multicenter, Open-label, Phase II Study of the Optimal Scheme of Administration of Pazopanib in Thyroid Carcinoma
• Date of first enrolment: March 2013
• Target sample size: 168
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01813136
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

France

Contacts

• Name: Christelle De La Fouchardière, MD
• Affiliation: Centre Léon Bérard; Lyon

Key inclusion & exclusion 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 pre


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Thyroid Carcinoma

Intervention(s)

Drug: Continuous pazopanib (Arm A)

Drug: Intermittent pazopanib (Arm B)

Primary Outcome(s)

Time to treatment failure (TTF) [Time Frame: up to 36 months]

Secondary Outcome(s)

Disease Control Rate (SDR) [Time Frame: 6 months after randomization]

Safety profile of pazopanib [Time Frame: up to 36 months]

Objective Response Rate (ORR) [Time Frame: 6 months after inclusion]

Overall Survival (OS) [Time Frame: up to 36 months]

Objective Response Rate (ORR) [Time Frame: 6 months after randomization]

Best response rate [Time Frame: up to 36 months]

Disease Control Rate (DCR) [Time Frame: 6 months after inclusion]

Progression-Free Survival (PFS) [Time Frame: up to 36 months]

Duration of response [Time Frame: up to 36 months]

Quality of Life (QoL) [Time Frame: At inclusion, randomization and at the end of pazopanib treatment]

Secondary ID(s)

2012-003162-41

PAZOTHYR

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

GlaxoSmithKline