Thyroid Cancer and Sunitinib (THYSU)

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT00510640
First received: August 1, 2007
Last updated: February 27, 2013
Last verified: February 2013
  Purpose

Due to arguments showing that angiogenesis could be involved in progression of metastatic thyroid carcinoma and to objective response during previous studies with sunitinib (an angiogenic oncology drug also known as Sutent), this study, THYSU, is justified to evaluate the efficacy of sunitinib in metastatic thyroid carcinoma. Furthermore, the standard treatment of metastatic thyroid carcinoma when a general treatment is to be prescribed is limited to radioiodine. When radioiodine becomes ineffective, there is no standard treatment despite some use of chemotherapy.

The objective of the trial is to determine the objective tumor response rate (efficacy) in patients with locally advanced or metastatic anaplastic, differentiated or medullary thyroid carcinoma treated with sunitinib; a secondary objective is to evaluate the safety of sunitinib in these patients.

The THYSU trial is a phase II, French multi-center study. This trial's plan is to enroll 75 patients with locally advanced or metastatic anaplastic, differentiated or medullar thyroid carcinoma.


Condition Intervention Phase
Cancer
Thyroid Carcinoma
Drug: Sunitinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 of Sunitinib (Sutent) in Patients With Locally Advanced or Metastatic Anaplastic, Differentiated or Medullar Thyroid Cancer

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • Objective response rate (ORR) : defined as the proportion of patients with confirmed complete (CR) or partial response (PR) according to the RECIST, relative to the total patients enrolled who received at least 1 dose of trial medication [ Time Frame: Every two cycles ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate the safety of sunitinib in patients with thyroid carcinoma [ Time Frame: After each cycle of treatment ] [ Designated as safety issue: Yes ]
  • Determine time-to-event variables of overall survival, time to: disease progression, response, and duration of response [ Time Frame: variable ] [ Designated as safety issue: No ]

Enrollment: 71
Study Start Date: August 2007
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sunitinib
Sunitinib will be administered orally daily for 4 weeks followed by a 2-week rest; the daily starting dose will be 50 mg with a provision for dose reduction based on tolerability. All patients will receive repeated cycles until disease progression or occurrence of severe toxicity.
Drug: Sunitinib
Capsule, 12.5 or 50 mg, starting dose level 50 mg daily

  Hide Detailed Description

Detailed Description:

The THYSU trial is a phase II trial of sunitinib (Sutent) in patients with locally advanced or metastatic anaplastic, differentiated or medullary thyroid carcinoma.

Due to arguments showing that angiogenesis could be involved in progression of metastatic thyroid carcinoma and to objective response during a phase I trial with sunitinib, it was justified to evaluate in a prospective trial the efficacy of sunitinib in metastatic thyroid carcinoma. Furthermore, the standard treatment of metastatic thyroid carcinoma when a general treatment is to be prescribed is limited to radioiodine. When radioiodine becomes ineffective, there is no standard treatment despite some usage of chemotherapy.

The objective of the trial is to determine the objective tumor response rate in patients with locally advanced or metastatic anaplastic, differentiated or medullary thyroid carcinoma treated with sunitinib, a secondary objective is to evaluate the safety of sunitinib in these patients with thyroid carcinoma.

The treatment of sunitinib is the standard dosage and schedule. Sunitinib is given orally at the dose of 50 mg daily for 28 days followed by 2 weeks of rest. Forthcoming cycles remain identical. Modification of the dose may use a lower dose at 37.5 mg or 25 mg given daily on the same schedule. All patients will receive repeated cycles of treatment until disease progression, occurrence of unacceptable toxicity, withdrawal of patient consent, or other withdrawal criteria are met. After discontinuation of treatment and the mandated 28-day follow up, patients will be followed only in order to collect information on further antineoplastic therapy and survival. In patients discontinuing treatment for reasons other than disease progression, tumor assessment will continue until disease progression, or initiation of other antineoplastic therapies.

The more frequent side effects are asthenia, mucositis, arterial hypertension, hand foot syndrome and diarrhea. Other side effects have been reported including nausea, vomiting, cutaneous events, decrease in left ventricular ejection fraction, neutropenia, and thrombopenia.

The patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial:

  • Patients must sign and date IRB/EC-approved informed consent.
  • Age ≥ 18.
  • Patients must have a life expectancy of at least 3 months and Karnofsky performance status ≥ 70%
  • Patients must have histologically confirmed TC
  • Tumor disease must be progressive (evidence of disease progression within 6 months)
  • Patients should not be candidates for surgical resection, external beam radiotherapy or radioiodine, and patients must not have more than one previous systemic treatment for cancer
  • Patients must have measurable disease defined by RECIST criteria as at least one lesion at least 2 cm in length by conventional CT techniques or at least 1 cm by spiral CT scan.
  • Resolution of all acute toxic effects of any prior treatment to NCI - CTCAE (version 3.0) grade < 1.
  • Patients must have discontinued from radiation therapy at least 4 weeks before first dose of study treatment and must have recovered from any toxic effects of treatment.
  • Blood pressure < 140 / 90 mmHg
  • Patients must have adequate organ function.
  • Patients with reproductive potential must use medically acceptable contraceptive method.
  • Willingness and ability to comply with the study procedures.
  • Patient affiliated with or profiting from a social security system

The presence of any non-inclusion criteria will exclude a patient from study enrollment.

Prior to undergoing any specific study procedures, patient and investigator sign informed consent. During the initial visit including verification of eligibility criteria, an interview with the patient is conducted regarding his/her recent and past clinical and treatment history (including oncology history). Physical examination including examination of major body systems, Karnofsky performance status, body weight, height, and vital signs is performed. Laboratory data are collected (hematology and chemistry, coagulation, thyroid tests, tumor markers and pregnancy test if applicable). Para clinic evaluations (12-lead ECGs and tumor imaging) are carried out. LVEF assessed by Echocardiogram or by MUGA scan (if necessary) and Brain Naturatic Peptide (Or NT pro-BNP) test are done.

During the follow-up, the patients are followed between the end of week 4 and week 6 by clinical and biological evaluation. Evaluation of tumor sites under sunitinib is planned every 2 cycles with CT scans. For patients with anaplastic or differentiated thyroid carcinoma, the first stage will include 21 efficacy-evaluable patients. An additional 29 efficacy-evaluable patients will be included at the second stage.

For patients with medullary thyroid carcinoma, the first stage will include 11 efficacy-evaluable patients. An additional 7 to 14 efficacy-evaluable patients will be included at the second stage.

10 French Oncology Departments are involved in this trial.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent.
  • Age ≥ 18.
  • Patients must have a life expectancy of at least 3 months
  • Patients must have a Karnofsky performance status ≥ 70%
  • Patients must have histologically confirmed thyroid cancer (TC)
  • Tumor disease must be progressive (evidence of disease progression within 6 months before starting the study for follicular and medullary thyroid cancer or symptomatic disease)
  • Patients should not be candidates for surgical resection, external beam radiotherapy or radioiodine
  • Patients must have measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST), such as at least one lesion at least 2 cm in length by conventional computed tomography (CT) techniques or at least 1 cm by spiral CT scan
  • Patients must not have more than one previous systemic treatment for cancer
  • Resolution of all acute toxic effects of any prior local treatment to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 3.0) grade < 1
  • Patients must have discontinued from radiation therapy at least 4 weeks before start of study treatment and must have recovered from any toxic effects of treatment
  • Blood pressure < 140 / 90 mmHg
  • Patients must have adequate organ function defined as: Platelets > 100 x 10*9/L, Hemoglobin > 8 g/dl, ANC > 1.5 x 10*9/L, Bilirubin < 3 mg/dL, AST and ALT < 2.5 x the upper limit of normal (ULN) or < 5 x the ULN for liver metastases, INR < 1.7 or prothrombin time < 6 sec over ULN, Serum creatinine < 1.5 x ULN
  • Patients with reproductive potential must use medically acceptable contraceptive methods (oral contraception or an intrauterine device [IUD])
  • Willingness and ability to comply with all study procedures
  • Affiliated or profit patient of a social security system

Exclusion Criteria:

  • Prior treatment on sunitinib or other anti-angiogenic therapy
  • NCI CTCAE grade 3 hemorrhage < 4 weeks of starting study treatment
  • Diagnosis of any second malignancy < 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma of the cervix uteri that has been adequately treated with no evidence of recurrent disease for 12 months
  • History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
  • Any of the following within the 12 months prior to study drug administration: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, including transient ischemic attack, or pulmonary embolism
  • Ongoing cardiac dysrhythmias of NCI CTCAE grade > 2, atrial fibrillation of any grade, or prolongation of the QTc interval to > 450 msec for males or > 470 msec for females
  • Left ventricular ejection fraction ( LVEF) < 50%
  • Hypertension that cannot be controlled by medications
  • Treatment with anticoagulant agents and treatment with therapeutic doses of warfarin currently or within 2 weeks prior to first day of sunitinib administration
  • Inability to swallow oral medications, or presence of active inflammatory bowel disease, partial or complete bowel obstruction or chronic diarrhea
  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness
  • Pregnancy or breastfeeding
  • Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study
  • Receipt of any investigational agent prior to study entry
  • Current treatment on another therapeutic clinical trial
  • Patient under safeguard of justice
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00510640

Locations
France
Centre Paul Papin - 2 rue Moll
Angers, France, 49100
Département Endocrinolo-Diabéto-Nutrition - CHU d'Angers - 4 rue de Larray
Angers, France, 49933
Service d'Oncologie Médicale et de Radiothérapie - Hôpital Saint André - 1 rue Jean Burguet
Bordeaux, France, 33075
Fédération Endocrinologie - Groupe Hospitalier Est - Hôpital neurologique - CHU Lyon - 59 Boulevard Pinel
Bron, France, 69677
Service d'Endocrinologie et maladies métaboliques, Clinique Marc Linquette - rue du Pr Laguesse
Lille, France, 59037
Centre Léon Bérard - Département de Médecine - 28 rue Laennec
Lyon, France, 69373
Service d'Endocrinologie, CHU Timone, AP-HM - 254 rue St Pierre
Marseille, France, 13385
Service des Maladies Endocriniennes - Hôpital Lapeyronie - 191 avenue du Doyen Gaston Giraud
Montpellier, France, 34295
Centre Paul Lamarque - Va d'Aurelle - CRLC Val d'Aurelle - 208 rue des Apothicaires
Montpellier, France, 34298
Service d'Endocrinologie - Hôpital de l'Archet I - Route Saint Antoine de Jinestière
Nice, France, 06202
Centre Antoine Lacassagne - 33 avenue de Valombrose
Nice, France, 06189
Service de Cancérologie Médicale - HEGP - 20 rue Leblanc
Paris, France, 75015
Service d'Oncologie Médicale, Institut Claudius Regaud - 20-24 rue du Pont Saint Pierre
Toulouse, France, 31052
Service d'endocrinologie et Maladies Métaboliques, Groupe Hospitalier Rangueil-Larrey CHU Toulouse - avenue Prof Jean Poulhes
Toulouse, France, 31059
Service d'Endocrinologie - CHU de Nancy, Hôpital de Brabois - rue du Morvan
Vandoeuvre les Nancy, France, 54511
Sponsors and Collaborators
University Hospital, Bordeaux
Pfizer
Investigators
Principal Investigator: Alain Ravaud, Pr. University Hospital, Bordeaux, France
Study Chair: Geneviève Chene, Pr. University Hospital, Bordeaux, France
  More Information

No publications provided

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT00510640     History of Changes
Other Study ID Numbers: 9277-06, 2006-23
Study First Received: August 1, 2007
Last Updated: February 27, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
thyroid carcinoma
Sunitinib
RECIST guidelines

Additional relevant MeSH terms:
Carcinoma
Thyroid Diseases
Thyroid Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014