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

NCT01813136 | Completed Phase 2 DMC

• 2 other identifiers: PAZOTHYR2012-003162-41
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 13

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.

Conditions

Thyroid Carcinoma

Keywords

radioiodine refractory Differentiated Thyroid Carcinoma; pazopanib; intermittent administration; time to treatment failure; TUTHYREF

Outcome Measures

Primary Outcomes (1)

• Time to treatment failure (TTF)

  TTF is the time to permanent treatment discontinuation due to any cause after randomization in each arm

  up to 36 months

Secondary Outcomes (10)

• Objective Response Rate (ORR)

  6 months after inclusion

• Disease Control Rate (DCR)

  6 months after inclusion

• Progression-Free Survival (PFS)

  up to 36 months

• Best response rate

  up to 36 months

• Duration of response

  up to 36 months

Other Outcomes (2)

• Identification of prognostic biomarkers of clinical outcome.

  At inclusion, day 56 and day 168 of treatment (before randomisation)

• Tissue expression of Raf-1 kinase inhibitory protein, PAX8, BRAF, Pi3KCA and Ras.

  At inclusion, day 56 and day 168 of treatment (before randomization)

Study Arms (2)

Continuous pazopanib (Arm A)

ACTIVE COMPARATOR

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

Drug: Continuous pazopanib (Arm A)

Intermittent pazopanib (Arm B)

EXPERIMENTAL

Temporary discontinuation of pazopanib at randomization, after an initial period of 6 cycles (28 days) of daily administration of pazopanib 800mg from inclusion until randomization. Pazopanib will be reintroduced for 6 cycles of 28 days, with daily administration of pazopanib 800mg, as soon as the patient relapses (progressive disease according to RECIST 1.1). At the end of this additional 6 cycles, study drug will be stopped a second time. This sequential scheme will be maintained until the patient experiences "on-treatment" progression

Drug: Intermittent pazopanib (Arm B)

Interventions

Continuous pazopanib (Arm A) DRUG

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

Also known as: GW786034

Continuous pazopanib (Arm A)

Intermittent pazopanib (Arm B) DRUG

Temporary discontinuation of pazopanib at randomization, after an initial period of 6 cycles (28 days) of daily administration of pazopanib 800mg from inclusion until randomization. Pazopanib will be reintroduced for 6 cycles of 28 days, with daily administration of pazopanib 800mg, as soon as the patient relapses (progressive disease according to RECIST 1.1). At the end of this additional 6 cycles, study drug will be stopped a second time. This sequential scheme will be maintained until the patient experiences "on-treatment" progression

Also known as: GW786034

Intermittent pazopanib (Arm B)

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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,

Sponsors & Collaborators

• Centre Leon Berard: lead
• GlaxoSmithKline: collaborator

Study Sites (13)

CHU Angers

Angers, 49933, France

Location

CHU Bordeaux

Bordeaux, 33075, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Centre François Baclesse

Caen, 14076, France

Location

CHRU Lille Hôpital Claude Huriez

Lille, 59037, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Hôpital de la Timone APHM

Marseille, 13385, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hôpital Saint-Louis APHP

Paris, 75010, France

Location

Hôpital de la Pitié Salpêtrière APHP

Paris, 75651, France

Location

Institut Jean Godinot

Reims, 51726, France

Location

Institut Claudius Régaud

Toulouse, 31052, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

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MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Christelle De La Fouchardière, MD

  Centre Léon Bérard, Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2013
• First Posted: March 18, 2013
• Study Start: March 1, 2013
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: August 16, 2019

Record last verified: 2019-08

Locations

FR (13)