Ovarian Cancer
Conditions
Keywords
ZD6474, Vandetanib, Zactima, Ovarian Cancer, Phase I, Phase II, Randomized, Safety
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.
Interventions
DRUGVandetanib
100mg doses orally, once daily
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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) |
| 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) |
| 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). |
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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. |
Countries
Germany
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Vandetanib 100 mg Once daily oral Vandetanib 100 mg added to standard therapy (pegylated liposomal doxorubicin 50 mg/m2 iv every 4 weeks) | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Vandetanib 100 mg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 3 / 14 |
Outcome results
Primary
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).
Time frame: From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vandetanib 100 mg | Description (on the Basis of the Safety Set): Safety and Tolerability by Means of Clinically Significant Laboratory Abnormalities. | 3 Participants |
Primary
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).
Time frame: From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vandetanib 100 mg | 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. | 2 Participants |
Primary
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)
Time frame: From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vandetanib 100 mg | Description (on the Basis of the Safety Set): Safety and Tolerability by Means of the Incidence and Type of Adverse Events (AEs). | 9 Participants |
Primary
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)
Time frame: From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vandetanib 100 mg | 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. | 5 Participants |
Primary
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)
Time frame: From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vandetanib 100 mg | 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. | 2 Participants |
Primary
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).
Time frame: From date of registration (Informed Consent Form completed) to date of last vist, up to 18 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vandetanib 100 mg | 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. | 5 Participants |
Secondary
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)
Time frame: From date of registration (Informed Consent Form completed) until the date of death.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vandetanib 100 mg | 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). | 11.1 Months |
Secondary
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.
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vandetanib 100 mg | 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). | 6.7 Months |