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

Primary Purpose

Ovarian Cancer

Status
Terminated
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Vandetanib
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring ZD6474, Vandetanib, Zactima, Ovarian Cancer, Phase I, Phase II, Randomized, Safety

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Vandetanib added to standard therapy (pegliposomal doxorubicin)

Outcomes

Primary Outcome Measures

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 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)
Description (on the Basis of the Safety Set): Safety and Tolerability by Means of Clinically Significant Laboratory Abnormalities.
Number of patients with elevated liver enzymes grade 3 (CTCAE grade 3=severe, CTCAE grade 4=life threatening).
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.
Number of participants with dermatologic skin reactions grade 3/4 (CTCAE grade 3= severe, CTCAE grade 4=life threatening)
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.
Number of participants with palmar-plantar erythrodysesthesia (PPE) grade 3/4 (CTCAE grade 3=severe skin changes with pain, CTCAE grade 4=life threatening).
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.
Number of participants with mucositis grade 3 (CTCAE grade 3=severe pain interfering with oral intake)
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.
Number of participants with neutropenia grade 3/4 (CTCAE grade 3=severe, CTCAE grade 4=life threatening).

Secondary Outcome Measures

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).
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.
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).
Median overall survival (OS)

Full Information

First Posted
March 16, 2009
Last Updated
August 29, 2016
Sponsor
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT00862836
Brief Title
Addition of Vandetanib to Standard Therapy Pegliposomal Doxorubicin (PLD)
Acronym
ZACFAST
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 Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Terminated
Why Stopped
Lack of efficacy
Study Start Date
April 2009 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
September 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
ZD6474, Vandetanib, Zactima, Ovarian Cancer, Phase I, Phase II, Randomized, Safety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Vandetanib added to standard therapy (pegliposomal doxorubicin)
Intervention Type
Drug
Intervention Name(s)
Vandetanib
Other Intervention Name(s)
Zactima
Intervention Description
100mg doses orally, once daily
Primary Outcome Measure Information:
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.
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.
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.
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.
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.
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.
Secondary Outcome Measure Information:
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.
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.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Ulm
State/Province
Baden-Württemberg
Country
Germany
Facility Name
Research Site
City
Wiesbaden
State/Province
Hessen
Country
Germany
Facility Name
Research Site
City
Essen
State/Province
Nordrhein-Westfalen
Country
Germany
Facility Name
Research Site
City
Kiel
State/Province
Schleswig-Holstein
Country
Germany
Facility Name
Research Site
City
Berlin
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
24005613
Citation
Harter P, Sehouli J, Kimmig R, Rau J, Hilpert F, Kurzeder C, Elser G, du Bois A. Addition of vandetanib to pegylated liposomal doxorubicin (PLD) in patients with recurrent ovarian cancer. A randomized phase I/II study of the AGO Study Group (AGO-OVAR 2.13). Invest New Drugs. 2013 Dec;31(6):1499-504. doi: 10.1007/s10637-013-0011-3. Epub 2013 Sep 5.
Results Reference
derived

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Addition of Vandetanib to Standard Therapy Pegliposomal Doxorubicin (PLD)

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