Neoplasms

Gland and Hormone Related Diseases

All Conditions

Diseases and Abnormalities at or Before Birth

Symptoms and General Pathology

Rare Diseases

Thyroid Neoplasms

Thyroid Diseases

Carcinoma

Carcinoma, Neuroendocrine

Carcinoma, Medullary

Endocrine Gland Neoplasms

Multiple Endocrine Neoplasia

Multiple Endocrine Neoplasia Type 2a

Endocrine System Diseases

Head and Neck Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neoplasms, Multiple Primary

Syndrome

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Thyroid Cancer, Medullary

Multiple Endocrine Neoplasia Type 2

Multiple Endocrine Neoplasia Type 2A

Neuroendocrine Tumor

Neuroepithelioma

ZD6474 (vandetanib)

Clinical Sciences & Operations

This will be a Phase II, open label study to establish the effect of once-daily oral doses of ZD6474 100mg in subjects with locally advanced or metastatic hereditary medullary thyroid cancer in whom no standard therapeutic option is available.

A Study To Assess ZD6474 (ZACTIMA™) Monotherapy In Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer

A Phase II, Open-Label Study To Assess The Efficacy and Tolerability of ZD6474 (ZACTIMA™ ) 100 mg Monotherapy In Subjects With Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer

The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as defined by RECIST criteria.

The categories for best objective response are CR, PR, stable disease (SD)\>= 12 weeks, progressive disease (PD) or NE.

Median progression free survival (months) estimated from a Weibull model with corresponding 95% confidence intervals. Progression free survival is the time from randomisation until objective disease progression (determined by RECIST assessments) or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment.

Disease control rate is defined as the number of patients who achieved disease control at 8 weeks following randomisation. Disease control at 8 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) \>= 24 weeks

Number of patients demonstrating an improvement from baseline to 24 weeks in WHO PS. Where WHO PS is the standard scale with patients scored (0 healthy - 5 dead) based on their physical capabilities

Symptomatic response will be defined as at least a 50% decrease in the stool frequency (represented by a persistent decrease in stool frequency over 4 weeks), taking as reference the baseline (mean) level.

A patient's best biochemical response was calculated from assessments performed at baseline and during treatment. Responders were those patients with a best biochemical response of CR or PR, confirmed by repeat assessments, which were to be performed no less than 4 weeks after the criteria for PR or CR were first met.

A patient's best biochemical response was calculated from assessments performed at baseline and during treatment. Responders were those patients with a best biochemical response of CR or PR, confirmed by repeat assessments, which were to be performed no less than 4 weeks after the criteria for Partial Response (PR) or Complete Response (CR) were first met.

Genzyme, a Sanofi Company

ZD6474 (ZACTIMA™) 100 mg

Age, Continuous

Gender

Trial Transparency Team

Objective Response Rate (ORR)

Progression-Free Survival (PFS)

Disease Control Rate (DCR)

World Heath Organization (WHO) Performance Status

Symptomatic Response

Biochemical Response Calcitonin (CTN )

Biochemical Response Carcinoembryonic Antigen CEA)

Overall Study

Daily oral dose of Caprelsa (vandetanib) 300mg

The purpose of this open label, two stage, phase II study is to evaluate the efficacy and tolerability of ZD6474 in patients with locally advanced or metastatic hereditary medullary thyroid carcinoma.

Efficacy and Tolerability of ZD6474 in Patients With Thyroid Cancer

An Open Label, Two Stage, Phase II Study to Evaluate the Efficacy and Tolerability of ZD6474 in Patients With Locally Advanced or Metastatic Hereditary Medullary Thyroid Carcinoma.

The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) defined according to RECIST 1.0.

Median time to progression defined according to RECIST 1.0 (months) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment.

Median duration of objective response as defined according to RECIST 1.0 from onset of response until data of objective disease progression or death from any cause in days.

Disease control rate was defined as the number of patients who had a best response of Complete Response (CR), or Partial Response (PR) or stable disease (SD) ≥24 weeks as defined according to RECIST 1.0.

A patient's best biochemical response was calculated from assessments performed at baseline and during treatment. Responders were those patients with a confirmed best biochemical response of Complete Response or Partial (i.e. complete normalization of CTN or at least a 50% decrease in CTN from baseline).

Number of participants with a reduction of frequency and improvement in consistency of stool to normal (no more than 2 solid stools daily without concomitant anti-diarrheal medication) following administration of Caprelsa (vandetanib) denoted a symptomatic CR. An improvement in stool consistency to mostly semisolid and decrease in stool frequency to 50% or greater denoted symptomatic PR.

Number of patients demonstrating a worsening (increase in score of one or more from baseline) in WHO PS from baseline to 24 weeks. WHO PS is scored zero (Fully active) to 4 (completely disabled)

Other (non-serious) adverse events terms were reported as per MedDRA 11.0.

Caprelsa (Vandetanib) 300 mg

Sex: Female, Male

Objective Response Rate

Progression Free Survival

Duration of Objective Response

Disease Control Rate

Biochemical Response Calcitonin (CTN)

World Health Organisation (WHO) Performance Status

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Disease Progression

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Bicalutamide

Androgens

Androgen Antagonists

Hormones

Hormone Antagonists

ZD6474 (Vandetanib)

Placebo

This randomized, double-blind phase II trial is to assess the efficacy and safety of bicalutamide (Casodex® ) associated to ZD6474 (Zactima™ ) or to placebo in patients with castration-refractory metastatic prostate cancer without any clinical symptom related to disease progression. The study is blinded, and subjects will be randomised (1:1 ratio) to either ZD6474 300 mg or placebo. The blinded design ensures robust, unbiased data collection and assessment. Placebo control is necessary to ensure a robust assessment of PSA PFS, and is acceptable in this subject population where all subjects will also received bicalutamide 150 mg o.d. Subjects will continue study treatment until they reach objective biological disease progression or unacceptable toxicity or withdrawal of consent or until end of trial (which event occurs first). The end of study is fixed 12 months after the last randomised patient's first dose of study treatment.

Efficacy and Safety of Zactima™ in Patients With Castration-refractory Metastatic Prostate Cancer

A Randomized, Double-blind Phase II Trial to Assess the Efficacy and Safety of Bicalutamide (Casodex® ) Associated to ZD6474 (Zactima™ ) or to Placebo in Patients With Castration-refractory Metastatic Prostate Cancer Without Any Clinical Symptom Related to Disease Progression

To assess the effect of vandetanib on biological progression free rate based on PSA level (assessable set).

PSA progression free rate defined as the number of participants with :

* After decline from baseline: a 25% increase above the nadir
* No decline from baseline: a 25% increase above the baseline (min. increase of 2 ng/mL)

Due to the difficulties to assess biological progression date when clinical progression has occurred first, and because of the non-assessment of the clinical progression after treatment discontinuation, Time to PSA progression was not evaluated. PFS was evaluated instead, whether biological or clinical progression.

Due to the difficulties to assess biological progression date when clinical progression has occurred first, and because of the non-assessment of the clinical progression after treatment discontinuation, Time to onset of cancer-related symptoms was not evaluated. PFS was evaluated instead, whether biological or clinical progression.

To investigate the effect of vandetanib on the PSA response rate. PSA response rate defined by the number of participants with a PSA decrease relative to baseline of at least 50%.

A minimum decrease of 2 ng/mL in absolute value and a confirmation on at least 2 consecutive occasions (at least 4 weeks apart) were requested.

To investigate the effect of vandetanib on overall survival. Patients alive at the time of the statistical analysis were censored at the time they were last known to be alive. Due to censored data, median overall survival in the placebo group cannot be calculated. OS defined as the number of participants who were alive.

To describe the effect of vandetanib on progression rate from the radionuclide bone scanning in a sub-group of patients who had a bone scan within 3 to 6 months after 1st treatment dose. Number of participants with at least 2 new lesions on the radionuclide bone scan compared to baseline assessment were counted for calculation of progression rate.

To investigate the effect of vandetanib on CTC. Numbering of CTCs to be performed at baseline, 1 week, 1 and 2 months after randomisation. This study was proposed only to patients followed in a study centre located in Ile de France.

Correlation between the number of CTCs and PSA response was to be estimated after 1 week, 1 and 2 months of treatment

To investigate the effect of vandetanib on CEC. Numbering of CECs was to be performed at baseline, 1 week, 1 month and 2 months after randomisation.

Correlation between the number of CECs and PSA response was to be estimated after 1 week, 1 month and 2 months of treatment.

To investigate the relationship between response to vandetanib, CTCs and CECs. To investigate gene signature profile of antiangiogenic response by gene micro-array analysis of CTCs.

Gene signature profile of CTCs was aimed to be compared before and after 2 months of treatment. No blood sample has been taken for the study, and so results on CTCs, CECs of tumour vessels and gene and signature profiles of CTCs were not performed.

Safety analysis set is composed with all randomized subjects who received at least one dose of treatment. One patient mistakenly received vandetanib during 3 days while randomized to placebo. This patient was accounted in the vandetanib group in the safety population. So, safety analysis set is composed with 48 Vandetanib and 47 placebo patients.

Bicalutamide 150mg + Vandetanib (ZD6474) 300mg

Vandetanib

Total

Prostate Specific Antigen (PSA) Progression Free Rate at 4 Months

Progression Free Survival (PFS) at 4 Months (Instead of Time to PSA Progression)

Progression Free Survival (PFS) at 4 Months (Instead of Time to Onset of Cancer-related Symptoms)

PSA Response Rate

Overall Survival (OS)

Progression Rate From the Radionuclide Bone Scanning

This part of the study was proposed only to patients followed in one study centre located in Ile de France and finally no blood sample has been taken at this centre. So no data on CTCs, CECs were collected and no analysis was performed.

Number of Circulating Tumour Cells (CTC) (in Patients Included in Ile de France Centres Only)

Number of Circulating Endothelial Cells (CEC) of Tumour Blood Cells (in Patients Included in Ile de France Centres Only)

Number of Patients With CECs, CTCs and Gene Signature Profile of CTCs

Respiratory Tract (Lung and Bronchial) Diseases

Nervous System Diseases

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Lung Neoplasms

Brain Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

100 mg as a once daily oral dose, 21 days

Whole Brain Radiotherapy (WBRT)

200 mg as a once daily oral dose, 21 days

ZD6474

300 mg as a once daily oral dose, 21 days

A clinical study to investigate the maximum tolerated dose of Vandetanib and concurrent WBRT in patients with NSCLC and brain metastases. All patients will receive WBRT, 10 fractions of 3 Gy. Patients will start 7 days prior to start of radiation treatment with Vandetanib. Total treatment time with Vandetanib is 3 weeks (21 days). Patients will have the opportunity to continue Vandetanib until progression at a dose of 300 mg. This multi-centre study will be conducted in a minimum of 9 patients and a maximum of 18 patients at 3 sites.

Investigate the Maximum Tolerated Dose of Vandetanib and Concurrent Whole Brain Radiotherapy (WBRT) in Patients With Non-small Cell Lung Cancer (NSCLC) and Brain Metastases

A Phase I Study of ZD6474 (Vandetanib) Concurrent With Whole Brain Radiotherapy for the Treatment of Brain Metastases in Patients With Non-small Cell Lung Cancer (NSCLC)

Sanofi

Carcinoma, Squamous Cell

Cisplatin

Radiation

The purpose of this study is to determine the maximum tolerated dose of ZD6474 given in combination with radiation or in combination with chemotherapy and radiation in patients with squamous cell carcinoma of the head and neck.

Open Label, Phase I ZD6474 Head and Neck Cancer Study

An Open Label Phase 1 Study to Assess the Maximum Tolerated Dose of ZACTIMA™ Given Concomitantly With Weekly Cisplatin Chemotherapy and Radiation Therapy in Patients With Previously Untreated, Unresected Stage III-IV Head and Neck Squamous Cell Carcinoma

Recurrence

Glioma

Glioblastoma

Astrocytoma

Oligodendroglioma

Gliosarcoma

Neoplasms, Neuroepithelial

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Oligoastrocytoma

Carboplatin

Sequential Group (carboplatin followed by vandetanib)

Vandetanib is an oral medication known to block angiogenesis and has shown significant antitumor activity in laboratory and animal studies. Vandetanib appears to be well tolerated by patients at specific daily doses.

Carboplatin is a drug that interrupts division of cancer cells and has been shown to be a useful drug in treatment of tumors known as gliomas. It is a useful drug for treating brain tumors, but researchers are interested in gathering more information about how it works as a treatment for patients who have not responded to initial surgery, radiation, or chemotherapy.

Katherine E Warren, M.D.

Background:

* Growth of new blood vessels (angiogenesis) provides many tumors, including brain tumors, with needed nutrients and oxygen for cancer cells to survive. One possible treatment for different kinds of cancer involves treatment with drugs that slow or stop angiogenesis and prevent further tumor growth.
* Vandetanib is an oral medication known to block angiogenesis and has shown significant antitumor activity in laboratory and animal studies. Vandetanib appears to be well tolerated by patients at specific daily doses.
* Carboplatin is a drug that interrupts division of cancer cells and has been shown to be a useful drug in treatment of tumors known as gliomas. It is a useful drug for treating brain tumors, but researchers are interested in gathering more information about how it works as a treatment for patients who have not responded to initial surgery, radiation, or chemotherapy.

Objective:

- To determine the safety and effectiveness of vandetanib and carboplatin, given together or sequentially, against recurrent high-grade gliomas.

Eligibility:

- Adults diagnosed with a malignant glioma who have received standard treatments that no longer appear to be effective.

Design:

* Patients will be assigned to one of two groups. Group 1 patients (combination group) will receive oral vandetanib for 28 days and intravenous (IV) carboplatin (once at the beginning of the 28-day cycle). Group 2 patients (sequential group) will receive IV carboplatin alone (once at the beginning of the 28-day cycle) and then oral vandetanib (300 mg daily) for 28 days if the tumor grows or the patient develops unacceptable carboplatin toxicity.
* Treatment will continue in 28-day cycles for 1 year for both groups.
* Patients will undergo a number of tests and procedures during the treatment cycle, including physical examinations, routine laboratory tests, electrocardiograms, and magnetic resonance imaging (MRI) scans
* At the end of 1 year of treatment, patients will be reevaluated for possible continuation of drug therapy.

Background:

In vivo experiments have documented the ability of vandetanib (ZD6474) to inhibit tumor growth in various preclinical tumor models. Given the pronounced neovasculature associated with malignant gliomas, and abundant published data demonstrating the dependence of glioma growth on the maintenance and proliferation of this neovasculature, vandetanib represents a potentially promising new therapeutic approach to these otherwise refractory tumors. Phase II data of vandetanib for recurrent glioblastomas conducted at the National Institutes of Health showed promising activity but responses were usually short-lasting.

Carboplatin has shown activity as monotherapy in the treatment of recurrent malignant gliomas in adults and preclinical data generated at Dr. Fines' laboratory demonstrate additive anti-glioma activity with vandetanib. The safety profile of carboplatin and the preclinical and clinical data supports its use in combination with vandetanib in patients with malignant gliomas.

Vandetanib is also an epidermal growth factor receptor (EGFR) inhibitor and it has been demonstrated that the presence of the EGFRvIII mutant and/or the presence of an intact phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and non-phosphorylated protein kinase B (AKT) predict for a higher likelihood of response to the EGFR inhibitors Tarceva and Iressa.

Objectives:

To establish data regarding the anti-tumor activity of vandetanib in combination with carboplatin and single agent carboplatin and to collect information regarding the spectrum of toxicities.

To determine if the presence of the EGFRvIII mutant and/or the presence of an intact PTEN and non-phosphorylated AKT predict for a higher likelihood of response to vandetanib.

Eligibility:

Patients with histologically proven malignant glioma are eligible for this study.

Design:

Patients will be randomized (1:1) to one of two groups. Patients in group one will be treated with vandetanib (300 mg daily for patients not on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg daily for patients on EIAEDs) and with carboplatin (area under the concentration-time curve at steady-state \[area under curve (AUC)\], 6mg/mL x min) once every 4-week cycle (combination group). Patients in group two will receive carboplatin alone (AUC 6mg/mL x min) once every 4-week cycle. Patients who develop tumor progression or unacceptable toxicity on carboplatin alone (group 2) can then receive single agent vandetanib (300 mg daily for patients not on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg daily for patients on EIAEDs) in 4-week cycles (sequential group). A total of 128 evaluable patients will be analyzed. The total accrual ceiling will allow for 74 patients to be enrolled in the glioblastoma multiforme (GBM) stratum and 74 patients in the anaplastic gliomas (AG) stratum (total 148) to factor in replacing those patients who come off treatment prior to cycle 1.

A Randomized Phase II Trial of Vandetanib (ZD6474) in Combination With Carboplatin Versus Carboplatin Alone Followed by Vandetanib Alone in Adults With Recurrent High-Grade Gliomas

Percentage of participants who are alive and progression-free at 6 months.

Time between the first day of treatment and the day of death.

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

National Cancer Institute (NCI)

Principal Investigator

Carboplatin: Carboplatin is a drug that interrupts division of cancer cells and has been shown to be a useful drug in treatment of tumors known as gliomas. It is a useful drug for treating brain tumors, but researchers are interested in gathering more information about how it works as a treatment for patients who have not responded to initial surgery, radiation, or chemotherapy.

ZD6474 (Vandetanib): Vandetanib is an oral medication known to block angiogenesis and has shown significant antitumor activity in laboratory and animal studies. Vandetanib appears to be well tolerated by patients at specific daily doses.

Carboplatin: Carboplatin is a drug that interrupts division of cancer cells and has been shown to be a useful drug in treatment of tumors known as gliomas. It is a useful drug for treating brain tumors, but researchers are interested in gathering more information about how it works as a treatment for patients who have not responded to initial surgery, radiation, or chemotherapy.

Vandetanib With Carboplatin

ZD6474 (Vandetanib): Vandetanib is an oral medication known to block angiogenesis and has shown significant antitumor activity in laboratory and animal studies. Vandetanib appears to be well tolerated by patients at specific daily doses.

Crossover to Vandetanib

Age, Categorical

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Katherine E. Warren

Glioblastoma (Combination)

Glioblastoma (Carboplatin Alone)

Anaplastic Astrocytomas (Combination)

Anaplastic Astrocytomas (Carboplatin Alone)

The group data is displayed per the report provided to the Food and Drug Administration.

Progression Free Survival at 6 Months

Glioblastoma (Carboplation Alone)

Anaplastic Astrocytoma (Combination)

Anaplastic Astrocytoma (Carboplatin Alone)

Overall Survival

Combo Group (both drugs together)

ZD6474 (Vandetanib): Vandetanib is an oral medication known to block angiogenesis and has shown significant antitumor activity in laboratory and animal studies. Vandetanib appears to be well tolerated by patients at specific daily doses.

Carboplatin: Carboplatin is a drug that interrupts division of cancer cells and has been shown to be a useful drug in treatment of tumors known as gliomas. It is a useful drug for treating brain tumors, but researchers are interested in gathering more information about how it works as a treatment for patients who have not responded to initial surgery, radiation, or chemotherapy.

Sequential Group (carboplatin followed by vandetanib)

ZD6474 (Vandetanib): Vandetanib is an oral medication known to block angiogenesis and has shown significant antitumor activity in laboratory and animal studies. Vandetanib appears to be well tolerated by patients at specific daily doses.

Carboplatin: Carboplatin is a drug that interrupts division of cancer cells and has been shown to be a useful drug in treatment of tumors known as gliomas. It is a useful drug for treating brain tumors, but researchers are interested in gathering more information about how it works as a treatment for patients who have not responded to initial surgery, radiation, or chemotherapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study To Assess ZD6474 (ZACTIMA™) Monotherapy In Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer	NCT00358956	Thyroid Cancer	ZD6474 (vandeta...	18 Years -	Sanofi
Efficacy and Tolerability of ZD6474 in Patients With Thyroid Cancer	NCT00098345	Thyroid Cancer	ZD6474 (vandeta...	18 Years - 130 Years	Sanofi
Efficacy and Safety of Zactima™ in Patients With Castration-refractory Metastatic Prostate Cancer	NCT00659438	Prostate Cancer	ZD6474 (Vandeta... Bicalutamide Placebo	18 Years -	Sanofi
Investigate the Maximum Tolerated Dose of Vandetanib and Concurrent Whole Brain Radiotherapy (WBRT) in Patients With Non-small Cell Lung Cancer (NSCLC) and Brain Metastases	NCT00807170	Non-small Cell ...	ZD6474 (Vandeta... Whole Brain Rad... ZD6474 ZD6474	18 Years -	Sanofi
Open Label, Phase I ZD6474 Head and Neck Cancer Study	NCT00450138	Head and Neck C...	ZD6474 (vandeta... Cisplatin Radiation	18 Years -	Sanofi
Investigate the Maximum Tolerated Dose of Vandetanib and Concurrent Whole Brain Radiotherapy (WBRT) in Patients With Non-small Cell Lung Cancer (NSCLC) and Brain Metastases	NCT00807170	Non-small Cell ...	ZD6474 (Vandeta... Whole Brain Rad... ZD6474 ZD6474	18 Years -	Sanofi
A Randomized Phase II Trial of Vandetanib (ZD6474) in Combination With Carboplatin Versus Carboplatin Alone Followed by Vandetanib Alone in Adults With Recurrent High-Grade Gliomas	NCT00995007	Glioblastoma Mu... Gliosarcoma Anaplastic Astr... Anaplastic Olig... Anaplastic Mixe...	ZD6474 (Vandeta... Carboplatin	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Open Label, Phase I ZD6474 Head and Neck Cancer Study	NCT00450138	Head and Neck C...	ZD6474 (vandeta... Cisplatin Radiation	18 Years -	Sanofi
An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer	NCT00410761	Thyroid Cancer	ZD6474 (Vandeta...	18 Years -	Sanofi

Spots Global Cancer Trial Database for zd6474 (vandetanib)