ZACFAST: Addition of Vandetanib to Standard Therapy Pegliposomal Doxorubicin (PLD)

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00862836
• Collaborator: (none)
• Enrollment: 15
• Locations: 5
• Arm: 1
• Duration (Months): 17
• Patients Per Site: 3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This multi-centre, non-randomized open phase I/randomized phase II study will be conducted in 70 patients (10 in phase I, 60 in phase II) with platinum-refractory recurrent epithelial cancer of the ovary, fallopian tube or peritoneum. A total of approximately 5 national centers will participate in phase I of the study. If the starting criteria for phase II of the study are met at the end of phase I, a total of approximately 20 national centers will participate in phase II of the study.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: Vandetanib	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Addition of Vandetanib to Standard Therapy (Pegliposomal Doxorubicin) in Patients With Recurrent Ovarian Cancer. A Multicentre Phase I / Randomized Phase II Study
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Vandetanib added to standard therapy (pegliposomal doxorubicin)	Drug: Vandetanib; 100mg doses orally, once daily; Other Names: Zactima

Outcome Measures

Primary Outcome Measures

1. Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). [From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.]

   Number of participants with at least 1 adverse event of grade 3 or higher (CTCAE grade 3=severe, CTCAE grade 4=life threatening/disabling, CTCAE grade 5=death, as defined by National Cancer Institute CTCAE, Version 3)

2. Description (on the Basis of the Safety Set): Safety and Tolerability by Means of Clinically Significant Laboratory Abnormalities. [From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.]

   Number of patients with elevated liver enzymes grade 3 (CTCAE grade 3=severe, CTCAE grade 4=life threatening).

3. Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). Number of Participants With Dermatologic Skin Reactions Grade 3/4. [From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.]

   Number of participants with dermatologic skin reactions grade 3/4 (CTCAE grade 3= severe, CTCAE grade 4=life threatening)

4. Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). Number of Participants With Palmar-plantar Erythrodysesthesia (PPE) Grade 3/4. [From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.]

   Number of participants with palmar-plantar erythrodysesthesia (PPE) grade 3/4 (CTCAE grade 3=severe skin changes with pain, CTCAE grade 4=life threatening).

5. Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). Number of Participants With Mucositis Grade 3. [From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.]

   Number of participants with mucositis grade 3 (CTCAE grade 3=severe pain interfering with oral intake)

6. Description (on the Basis of the Safety Set): Safety and Tolerability by Means of Clinically Significant Laboratory Abnormalities. Number of Participants With Neutropenia Grade 3/4. [From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.]

   Number of participants with neutropenia grade 3/4 (CTCAE grade 3=severe, CTCAE grade 4=life threatening).

Secondary Outcome Measures

1. Evaluation (for ITT Set): Clinical Activity of Once Daily Oral Vandetanib 100 mg When Added to Standard Therapy (See Above), by Assessment of Progression Free Survival (PFS). [From date of registration (Informed Consent Form completed) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months.]

   Progression Free Survival: Progression is defined using RECIST, as a measurable increase of at least 20% in the sum of longest diameters of target lesions or unequivocal progression of non-target lesions, or the appearance of new lesions, since baseline.

2. Evaluation (for ITT Set): Clinical Activity of Once Daily Oral Vandetanib 100 mg When Added to Standard Therapy (See Above), by Assessment of Overall Survival (OS). [From date of registration (Informed Consent Form completed) until the date of death.]

   Median overall survival (OS)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histopathologically documented invasive epithelial ovarian carcinoma, cancer of the fallopian tube or the peritoneum refractory to platinum-based chemotherapy or with partially platinum sensitive disease.

• Planned therapy with pegylated liposomal doxorubicin 50 mg/m² for recurrent platinum-refractory ovarian cancer.

• Patients with a progression-free-interval of 6 to 12 months after platinum-based chemotherapy are only eligible if a further course of platinum-based combination chemotherapy is not possible as judged by the investigator(s).

• Patients must have received at least one previous platinum- and taxane-based chemotherapy regimen.

Exclusion Criteria:

• Brain metastases or spinal cord compression, unless treated at least 4 weeks before first dose and stable without steroid treatment for 10 days

• Any concomitant medications that may cause QTc prolongation or induce Torsades de Pointes or induce CYP3A4 function

• Treatment with mouse-antibodies in patients with evaluable disease and CA-125 progressive disease in the last 3 months. These patients are only eligible in case of measurable disease according to RECIST or cytological/histological proven relapse

• More than two prior lines of chemotherapy.

• Any chemotherapy or other systemic anti-cancer therapy within four weeks prior to randomization.

• Radiation therapy within the last 4 weeks prior to randomization (with the exception of palliative radiotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Ulm	Baden-Württemberg	Germany
2	Research Site	Wiesbaden	Hessen	Germany
3	Research Site	Essen	Nordrhein-Westfalen	Germany
4	Research Site	Kiel	Schleswig-Holstein	Germany
5	Research Site	Berlin		Germany

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00862836
• Other Study ID Numbers: D4200C00083; 2008-005557-38
• First Posted: Mar 17, 2009
• Last Update Posted: Oct 10, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Genzyme, a Sanofi Company: ZD6474; Vandetanib; Zactima; Ovarian Cancer; Phase I; Phase II; Randomized; Safety
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Study Results

Participant Flow

Pre-assignment Detail	Phase I of the trial consisted of a safety run-in phase of 10 patients with histologically confirmed, epithelial ovarian carcinoma, cancer of the fallopian tube or the peritoneum refractory or partially sensitive to platinum-based therapy evaluable for at least 2 cycles. Phase II of the trial was not conducted.

Arm/Group Title	Vandetanib 100 mg
Arm/Group Description	Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
Period Title: Overall Study
STARTED	15
Evaluable for Safety/Toxicity	14
Evaluable for Activity (Tumour Response)	10
COMPLETED	14
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Vandetanib 100 mg
Arm/Group Description	Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 80%
>=65 years	3 20%
Sex: Female, Male (Count of Participants)
Female	15 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs).
Description	Number of participants with at least 1 adverse event of grade 3 or higher (CTCAE grade 3=severe, CTCAE grade 4=life threatening/disabling, CTCAE grade 5=death, as defined by National Cancer Institute CTCAE, Version 3)
Time Frame	From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg
Arm/Group Description	Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
Measure Participants	14
Number [Participants]	9 60%

2. Secondary Outcome

Title	Evaluation (for ITT Set): Clinical Activity of Once Daily Oral Vandetanib 100 mg When Added to Standard Therapy (See Above), by Assessment of Progression Free Survival (PFS).
Description	Progression Free Survival: Progression is defined using RECIST, as a measurable increase of at least 20% in the sum of longest diameters of target lesions or unequivocal progression of non-target lesions, or the appearance of new lesions, since baseline.
Time Frame	From date of registration (Informed Consent Form completed) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg
Arm/Group Description	Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
Measure Participants	10
Median (95% Confidence Interval) [Months]	6.7

3. Secondary Outcome

Title	Evaluation (for ITT Set): Clinical Activity of Once Daily Oral Vandetanib 100 mg When Added to Standard Therapy (See Above), by Assessment of Overall Survival (OS).
Description	Median overall survival (OS)
Time Frame	From date of registration (Informed Consent Form completed) until the date of death.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg
Arm/Group Description	Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
Measure Participants	10
Median (95% Confidence Interval) [Months]	11.1

4. Primary Outcome

Title	Description (on the Basis of the Safety Set): Safety and Tolerability by Means of Clinically Significant Laboratory Abnormalities.
Description	Number of patients with elevated liver enzymes grade 3 (CTCAE grade 3=severe, CTCAE grade 4=life threatening).
Time Frame	From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg
Arm/Group Description	Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
Measure Participants	14
Number [Participants]	3 20%

5. Primary Outcome

Title	Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). Number of Participants With Dermatologic Skin Reactions Grade 3/4.
Description	Number of participants with dermatologic skin reactions grade 3/4 (CTCAE grade 3= severe, CTCAE grade 4=life threatening)
Time Frame	From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg
Arm/Group Description	Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
Measure Participants	14
Number [Participants]	5 33.3%

6. Primary Outcome

Title	Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). Number of Participants With Palmar-plantar Erythrodysesthesia (PPE) Grade 3/4.
Description	Number of participants with palmar-plantar erythrodysesthesia (PPE) grade 3/4 (CTCAE grade 3=severe skin changes with pain, CTCAE grade 4=life threatening).
Time Frame	From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg
Arm/Group Description	Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
Measure Participants	14
Number [Participants]	5 33.3%

7. Primary Outcome

Title	Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). Number of Participants With Mucositis Grade 3.
Description	Number of participants with mucositis grade 3 (CTCAE grade 3=severe pain interfering with oral intake)
Time Frame	From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg
Arm/Group Description	Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
Measure Participants	14
Number [Participants]	2 13.3%

8. Primary Outcome

Title	Description (on the Basis of the Safety Set): Safety and Tolerability by Means of Clinically Significant Laboratory Abnormalities. Number of Participants With Neutropenia Grade 3/4.
Description	Number of participants with neutropenia grade 3/4 (CTCAE grade 3=severe, CTCAE grade 4=life threatening).
Time Frame	From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg
Arm/Group Description	Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
Measure Participants	14
Number [Participants]	2 13.3%

Adverse Events

Arm/Group Title	Vandetanib 100 mg
Arm/Group Description	Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks)
All Cause Mortality
	Vandetanib 100 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vandetanib 100 mg
	Affected / at Risk (%)	# Events
Total	3/14 (21.4%)
Cardiac disorders
Arrhythmia	1/14 (7.1%)
Gastrointestinal disorders
Abdominal pain	1/14 (7.1%)
Ascites	1/14 (7.1%)
Ileus	1/14 (7.1%)
Nausea	1/14 (7.1%)
Vomiting	1/14 (7.1%)
General disorders
General physical health deterioration	1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/14 (7.1%)
Other (Not Including Serious) Adverse Events
	Vandetanib 100 mg
	Affected / at Risk (%)	# Events
Total	14/14 (100%)
Blood and lymphatic system disorders
Anaemia	1/14 (7.1%)
Leukopenia	1/14 (7.1%)
Neutropenia	1/14 (7.1%)
Thrombocytopenia	1/14 (7.1%)
Thrombocytosis	1/14 (7.1%)
Cardiac disorders
Angina pectoris	1/14 (7.1%)
Tachyarrhythmia	1/14 (7.1%)
Gastrointestinal disorders
Diarrhoea	7/14 (50%)
Nausea	7/14 (50%)
Constipation	4/14 (28.6%)
Vomiting	4/14 (28.6%)
Abdominal pain	3/14 (21.4%)
Dyspepsia	3/14 (21.4%)
Stomatitis	3/14 (21.4%)
Dysphagia	2/14 (14.3%)
Oesophagitis	2/14 (14.3%)
Flatulence	1/14 (7.1%)
Gingivitis	1/14 (7.1%)
Oesophageal pain	1/14 (7.1%)
General disorders
Fatigue	6/14 (42.9%)
Mucosal inflammation	6/14 (42.9%)
Chills	1/14 (7.1%)
Mucosal dryness	1/14 (7.1%)
Oedema peripheral	1/14 (7.1%)
Immune system disorders
Hypersensitivity	1/14 (7.1%)
Infections and infestations
Localised infection	1/14 (7.1%)
Nasopharyngitis	1/14 (7.1%)
Urinary tract infection	1/14 (7.1%)
Rhinitis	1/14 (7.1%)
Investigations
Gamma-glutamyltransferase	6/14 (42.9%)
Aspartate aminotransferase	5/14 (35.7%)
White blood cell count	5/14 (35.7%)
Alanine aminotransferase	4/14 (28.6%)
Blood alkaline phosphatase	4/14 (28.6%)
Blood creatinine	3/14 (21.4%)
Blood lactate dehydrogenase	3/14 (21.4%)
Haemoglobin	3/14 (21.4%)
Blood glucose	2/14 (14.3%)
Monocyte count	2/14 (14.3%)
Protein total	2/14 (14.3%)
Activated partial thromboplastin time	1/14 (7.1%)
Alanine aminotransferase increased	1/14 (7.1%)
Aspartate aminotransferase increased	1/14 (7.1%)
Blood bilirubin	1/14 (7.1%)
Blood calcium	1/14 (7.1%)
Blood chloride	1/14 (7.1%)
Blood glucose increased	1/14 (7.1%)
Blood lactate dehydrogenase increased	1/14 (7.1%)
Blood magnesium decreased	1/14 (7.1%)
Blood potassium	1/14 (7.1%)
Haematocrit	1/14 (7.1%)
Haematocrit decreased	1/14 (7.1%)
Haemoglobin decreased	1/14 (7.1%)
Monocyte count decreased	1/14 (7.1%)
Neutrophil count	1/14 (7.1%)
Neutrophil count increased	1/14 (7.1%)
Prothrombin time	1/14 (7.1%)
International normalised ratio	1/14 (7.1%)
Metabolism and nutrition disorders
Hypocalcaemia	2/14 (14.3%)
Decreased appetite	1/14 (7.1%)
Hypoglycaemia	1/14 (7.1%)
Hypomagnesaemia	1/14 (7.1%)
Hyponatraemia	1/14 (7.1%)
Hypoproteinaemia	1/14 (7.1%)
Musculoskeletal and connective tissue disorders
Back pain	1/14 (7.1%)
Muscle spasms	1/14 (7.1%)
Nervous system disorders
Headache	4/14 (28.6%)
Peripheral sensory neuropath	1/14 (7.1%)
Psychiatric disorders
Sleep disorder	2/14 (14.3%)
Insomnia	1/14 (7.1%)
Chromaturia	1/14 (7.1%)
Renal and urinary disorders
Renal pain	1/14 (7.1%)
Reproductive system and breast disorders
Breast pain	1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/14 (21.4%)
Epistaxis	2/14 (14.3%)
Cough	1/14 (7.1%)
Dyspnoea exertional	1/14 (7.1%)
Oropharyngeal pain	1/14 (7.1%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	7/14 (50%)
Rash	4/14 (28.6%)
Nail disorder	2/14 (14.3%)
Acne	1/14 (7.1%)
Alopecia	1/14 (7.1%)
Dry skin	1/14 (7.1%)
Eczema	1/14 (7.1%)
Erythema	1/14 (7.1%)
Heat rash	1/14 (7.1%)
Pruritus	1/14 (7.1%)
Skin toxicity	1/14 (7.1%)
Vascular disorders
Flushing	1/14 (7.1%)
Hot flush	1/14 (7.1%)

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.