Evaluate the Safety and Tolerability of Vandetanib in Japanese Patients With Medullary Thyroid Carcinoma

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01661179
• Collaborator: (none)
• Enrollment: 14
• Locations: 4
• Arm: 1
• Duration (Months): 19.9
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Open-label Study to Evaluate the Safety and Tolerability of Vandetanib 300 mg/day in Japanese Patients with Unresectable Locally Advanced or Metastatic Medullary Thyroid Carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Unresectable Locally Advanced or Metastatic, Medullary Thyroid Carcinoma	Drug: Vandetanib 300mg	Phase 1/Phase 2

Detailed Description

A Phase I/II, Open-label Study to Evaluate the Safety and Tolerability of Vandetanib 300 mg/day in Japanese Patients with Unresectable Locally Advanced or Metastatic Medullary Thyroid Carcinoma

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II, Open-label Study to Evaluate the Safety and Tolerability of Vandetanib 300 mg/Day in Japanese Patients With Unresectable Locally Advanced or Metastatic Medullary Thyroid Carcinoma
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vandetanib 300mg 300 mg/day vandetanib	Drug: Vandetanib 300mg; 300 mg oral dose once daily (100 mg x 3 tablets); Other Names: ZD6474

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate Within the First 56 Weeks After the First Dose of Vandetanib [Sept 2012 to May 2014]

   ORR is defined as the percentage of patients who have a confirmed CR (Disappearance of all target lesions) or PR (>=30% decrease in the sum of diameters of target lesions) prior to any evidence of progression as defined by RECIST V1.1. This percentage is calculated with only patients who had at least measurable lesion in the efficacy analysis set.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written consent from female or male Japanese patients aged 20 years and over. Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status.

• Previous diagnosis of unresectable, locally advanced or metastatic, hereditary or sporadic Medullary Thyroid Carcinoma(MTC).

• Patients who have a good overall health status(World Health Organization (WHO) Performance status 0-2).

• Patients who have appropriate renal conditions confirmed by test results for taking part in the study.

• For patients with measurable disease(at least one lesion, not irradiated within 12 weeks of study registration, with longest diameter more or equal 10mm (lymph nodes minimum more or equal 15 mm) with CT or MRI).

Exclusion Criteria:

• Patients with brain metastases or spinal cord compression.

• Patients with significant abnormal ECG (QTcB correction unmeasurable or more than 480 ms)findings and /or significant cardiac conditions or events, uncontrolled hypertension and evidence of severe lung disease.

• Abnormal electrolytes such as potassium, magnesium and calcium, or abnormal organ functions such as decreased creatinine clearance.

• Patients with significant abnormal laboratory findings (to include abnormal liver function tests (bilirubin more than 1.5xULRR, and ALT, AST, or ALP more than 2.5xULRR or 5.0xULRR if related to liver metastases).

• Prior treatment (major surgery, radiation therapy, chemotherapy, or other investigational drugs) received within 28 days before registration.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Fukuoka-shi		Japan
2	Research Site	Kobe-shi		Japan
3	Research Site	Koto-ku		Japan
4	Research Site	Shinjuku-ku		Japan

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, MD, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• CSR Synopsis

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01661179
• Other Study ID Numbers: D4200C00098
• First Posted: Aug 9, 2012
• Last Update Posted: Dec 5, 2016
• Last Verified: Oct 1, 2016

• Keywords provided by Genzyme, a Sanofi Company: Medullary Thyroid Carcinoma; Medullary Thyroid Cancer; Vandetanib
• Additional relevant MeSH terms: Carcinoma; Thyroid Neoplasms; Carcinoma, Neuroendocrine; Thyroid Diseases

Study Results

Participant Flow

Recruitment Details	From 12 November 2012 to 18 June 2013, 14 participants were treated by 4 centers in Japan to receive vandetanib.
Pre-assignment Detail	16 participants were screened; 14 participants were treated.

Arm/Group Title	Vandetanib 300 mg
Arm/Group Description	Vandetanib at 300 mg using 3 x 100 mg vandetanib tablets were dosed orally, once daily
Period Title: Overall Study
STARTED	14
COMPLETED	8
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Vandetanib 300 mg
Arm/Group Description	Vandetanib at 300 mg using 3 x 100 mg vandetanib tablets were dosed orally, once daily
Overall Participants	14
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.6 (10.21)
Age, Customized (Number) [Number]
>=20 - <50 years	6 42.9%
>=50 - <65 years	7 50%
>=65 years	1 7.1%
Sex: Female, Male (Count of Participants)
Female	7 50%
Male	7 50%
Race/Ethnicity, Customized (Number) [Number]
Asian	14 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate Within the First 56 Weeks After the First Dose of Vandetanib
Description	ORR is defined as the percentage of patients who have a confirmed CR (Disappearance of all target lesions) or PR (>=30% decrease in the sum of diameters of target lesions) prior to any evidence of progression as defined by RECIST V1.1. This percentage is calculated with only patients who had at least measurable lesion in the efficacy analysis set.
Time Frame	Sept 2012 to May 2014

Outcome Measure Data

Analysis Population Description

All patients with post-baseline efficacy assessments

Arm/Group Title	Vandetanib 300 mg
Arm/Group Description	Vandetanib at 300 mg using 3 x 100 mg vandetanib tablets were dosed orally, once daily
Measure Participants	13
Number (95% Confidence Interval) [percentage of participants]	38.5 275%

Adverse Events

Arm/Group Title	Vandetanib 300 mg
Arm/Group Description	Vandetanib at 300 mg using 3 x 100 mg vandetanib tablets were dosed orally, once daily
All Cause Mortality
	Vandetanib 300 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vandetanib 300 mg
	Affected / at Risk (%)	# Events
Total	4/14 (28.6%)
Gastrointestinal disorders
Ascites	1/14 (7.1%)	1
General disorders
Fatigue	1/14 (7.1%)	1
Malaise	1/14 (7.1%)	1
Infections and infestations
Pyelonephritis	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	1/14 (7.1%)	1
Other (Not Including Serious) Adverse Events
	Vandetanib 300 mg
	Affected / at Risk (%)	# Events
Total	14/14 (100%)
Blood and lymphatic system disorders
Eosinophilia	1/14 (7.1%)	1
Cardiac disorders
Palpitations	3/14 (21.4%)	3
Supraventricular extrasystoles	1/14 (7.1%)	1
Ear and labyrinth disorders
Vertigo	2/14 (14.3%)	2
Eye disorders
Chalazion	1/14 (7.1%)	1
Corneal opacity	5/14 (35.7%)	5
Dry eye	2/14 (14.3%)	2
Eyelid function disorder	1/14 (7.1%)	1
Keratitis	1/14 (7.1%)	1
Keratopathy	1/14 (7.1%)	1
Meibomian gland dysfunction	2/14 (14.3%)	2
Vision blurred	1/14 (7.1%)	1
Punctate keratitis	1/14 (7.1%)	1
Gastrointestinal disorders
Abdominal pain upper	1/14 (7.1%)	1
Dyspepsia	1/14 (7.1%)	1
Gastritis	1/14 (7.1%)	1
Haemorrhoidal haemorrhage	1/14 (7.1%)	1
Nausea	5/14 (35.7%)	6
Cheilitis	1/14 (7.1%)	1
Constipation	2/14 (14.3%)	2
Diarrhoea	11/14 (78.6%)	17
Dry mouth	1/14 (7.1%)	1
Glossitis	1/14 (7.1%)	1
Stomatitis	4/14 (28.6%)	6
Vomiting	2/14 (14.3%)	2
General disorders
Fatigue	3/14 (21.4%)	5
Non-cardiac chest pain	1/14 (7.1%)	1
Pyrexia	4/14 (28.6%)	8
Malaise	2/14 (14.3%)	2
Mucosal erosion	1/14 (7.1%)	1
Oedema	4/14 (28.6%)	4
Oedema mucosal	1/14 (7.1%)	1
Pain	1/14 (7.1%)	2
Infections and infestations
Anisakiasis	1/14 (7.1%)	1
Tinea pedis	1/14 (7.1%)	1
Bronchitis	1/14 (7.1%)	1
Cystitis	1/14 (7.1%)	1
Dermatitis infected	1/14 (7.1%)	1
Gastroenteritis	1/14 (7.1%)	1
Herpes zoster	1/14 (7.1%)	1
Laryngitis	1/14 (7.1%)	1
Nasopharyngitis	3/14 (21.4%)	4
Paronychia	3/14 (21.4%)	3
Rash pustular	1/14 (7.1%)	1
Upper respiratory tract infection	1/14 (7.1%)	1
Urinary tract infection	1/14 (7.1%)	1
Vaginitis bacterial	1/14 (7.1%)	1
Vulvovaginal candidiasis	1/14 (7.1%)	1
Wound infection	1/14 (7.1%)	1
Injury, poisoning and procedural complications
Thermal burn	1/14 (7.1%)	1
Investigations
Alanine aminotransferase increased	1/14 (7.1%)	1
Aspartate aminotransferase increased	1/14 (7.1%)	1
Blood alkaline phosphatase increased	1/14 (7.1%)	1
Electrocardiogram QT prolonged	3/14 (21.4%)	5
Haemoglobin increased	1/14 (7.1%)	1
Weight decreased	2/14 (14.3%)	2
Blood calcium increased	1/14 (7.1%)	1
Blood creatinine increased	2/14 (14.3%)	2
Blood magnesium decreased	1/14 (7.1%)	1
Red blood cell count increased	1/14 (7.1%)	1
Weight increased	1/14 (7.1%)	1
Metabolism and nutrition disorders
Decreased appetite	5/14 (35.7%)	6
Dehydration	2/14 (14.3%)	2
Hypocalcaemia	2/14 (14.3%)	4
Hypokalaemia	1/14 (7.1%)	1
Hypomagnesaemia	1/14 (7.1%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/14 (7.1%)	1
Arthritis	2/14 (14.3%)	2
Muscle spasms	1/14 (7.1%)	1
Musculoskeletal chest pain	1/14 (7.1%)	1
Neck pain	1/14 (7.1%)	1
Nervous system disorders
Dysgeusia	2/14 (14.3%)	2
Headache	2/14 (14.3%)	2
Somnolence	1/14 (7.1%)	1
Syncope	1/14 (7.1%)	1
Tremor	1/14 (7.1%)	1
Peripheral sensory neuropathy	2/14 (14.3%)	2
Dizziness	4/14 (28.6%)	4
Psychiatric disorders
Anxiety	1/14 (7.1%)	1
Insomnia	1/14 (7.1%)	1
Restlessness	1/14 (7.1%)	1
Renal and urinary disorders
Haematuria	2/14 (14.3%)	3
Nephrolithiasis	1/14 (7.1%)	1
Proteinuria	5/14 (35.7%)	5
Renal impairment	2/14 (14.3%)	2
Respiratory, thoracic and mediastinal disorders
Cough	2/14 (14.3%)	2
Dysphonia	3/14 (21.4%)	3
Dyspnoea	1/14 (7.1%)	1
Dyspnoea exertional	2/14 (14.3%)	2
Epistaxis	2/14 (14.3%)	2
Hiccups	1/14 (7.1%)	1
Skin and subcutaneous tissue disorders
Alopecia	4/14 (28.6%)	4
Dermatitis acneiform	2/14 (14.3%)	2
Dry skin	1/14 (7.1%)	1
Ingrowing nail	2/14 (14.3%)	2
Onychomadesis	1/14 (7.1%)	1
Palmar-plantar erythrodysaesthesia syndrome	4/14 (28.6%)	4
Pruritus	2/14 (14.3%)	2
Rash	6/14 (42.9%)	6
Rash maculo-papular	5/14 (35.7%)	5
Vascular disorders
Hypertension	9/14 (64.3%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.