Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer
Conditions
Keywords
recurrent ovarian epithelial cancer, recurrent fallopian tube cancer, recurrent primary peritoneal cavity cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether docetaxel is more effective when given alone or together with vandetanib. PURPOSE: This randomized phase II trial is studying docetaxel given together with or without vandetanib to see how well it works in treating patients with persistent or recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.
Detailed description
OBJECTIVES: * To evaluate the clinical efficacy of docetaxel and vandetanib relative to docetaxel alone in patients with platinum-resistant, recurrent, refractory, or progressive/persistent ovarian epithelial, primary peritoneal, or fallopian tube cancer, as measured by progression-free survival. * To evaluate the response rate (complete and partial) and duration of overall survival of these patients. * To evaluate the response (complete and partial) and time to treatment failure after treatment with single agent vandetanib following progression on single agent docetaxel. * To evaluate the frequency and severity of adverse events as assessed by Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0. * To evaluate the toxicity of single agent vandetanib following docetaxel as assessed by CTCAE v4.0. OUTLINE: Patients are stratified according to prior treatment with antiangiogenesis agents (yes vs no). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who progress also receive oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of a second disease progression or unacceptable toxicity. * Arm II: Patients receive docetaxel IV over 1 hour on day 1 and oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.
Interventions
DRUGdocetaxel
Given IV
DRUGvandetanib
Given orally
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal carcinoma * Recurrent, refractory, or progressive/persistent disease * Measurable or non-measurable disease documented by CT scan of the abdomen and pelvis * Must have received 1 prior platinum-based chemotherapy regimen for management of primary disease containing carboplatin, cisplatin, or other organoplatinum compound * Initial treatment may have included any of the following: * High-dose therapy * Consolidation therapy * Non-cytotoxic agent therapy * Extended therapy administered after surgical or non-surgical assessment * Additional cytotoxic regimen for recurrent, refractory, or progressive/persistent disease, including re-treatment with primary treatment regimen * No more than 3 prior regimens for recurrent, refractory, persistent, or progressive disease. PATIENT CHARACTERISTICS: * Zubrod performance status 0-2 * Absolute neutrophil count (ANC) ≥ 1,500/mcl * Platelet count ≥ 100,000/mcl * Serum creatinine normal OR calculated creatinine clearance ≥ 30 mL/min * Urine protein:creatinine ratio \< 1 * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * aspartate aminotransferase - alanine aminotransferase (AST or ALT) ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases are present) * Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases are present) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for ≥ 6 months after completion of vandetanib therapy * No neuropathy ≥ grade 2 CTCAE v4.0 * No active infection requiring systemic or intravenous antibiotics * No significant traumatic injury within the past 28 days * No significant cardiovascular disease, including any of the following: * Uncontrolled hypertension (i.e., systolic blood pressure \[BP\] \> 140 mm Hg or diastolic BP \> 90 mm Hg) within the past 28 days * Myocardial infarction superior vena cava syndrome, or New York Heart Association (NYHA) class II-IV heart disease within the past 3 months * Presence of left bundle branch block * Congenital long QT syndrome or first degree relative with unexplained sudden death \< 40 years of age * QT interval with Bazett's correction that is unmeasurable or ≥ 480 msec by screening ECG * History of symptomatic arrhythmia (i.e., multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) requiring treatment (≥ CTCAE grade 3) or asymptomatic sustained ventricular tachycardia * Atrial fibrillation controlled on medication allowed PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from all prior therapy (except alopecia) to NCI CTCAE v3.0 grade ≤ 1 * No prior vandetanib * Treatment with other anti-vascular endothelial growth factor (VEGF) targeted therapy allowed * No prior docetaxel or any non-cytotoxic therapy (excluding hormonal therapy) for recurrent disease, regardless of whether it was part of primary treatment * Prior docetaxel as part of front-line cytotoxic regimen (including maintenance therapy) allowed as long as no disease progression on or within 6 months after receiving docetaxel * At least 7 days since prior hormonal therapy for the malignant tumor * Concurrent hormone replacement therapy for menopausal symptoms allowed * At least 28 days since other prior therapy for the malignant tumor, including immunologic agents * More than 7 days since prior minor surgical procedures, fine needle aspirates, or core biopsies * More than 14 days since prior and no concurrent potent inducers of cytochrome P450 3A4 (CYP3A4) function * More than 14 days since prior and no concurrent medications having a risk of causing Torsades de Pointes or risk of QTc prolongation * Patients receiving a drug that has a risk of QTc prolongation must not have QTc ≥ 460 msec * More than 28 days since prior investigational agents for any purpose * More than 28 days since prior and no concurrent major surgical procedure or open biopsy * More than 5 years since prior chemotherapy for abdominal or pelvic tumor, except treatment of ovarian, fallopian tube, or primary peritoneal cancer * Prior adjuvant chemotherapy for localized breast cancer allowed, provided it was completed more than 3 years prior to study, and the patient remains free of recurrent or metastatic disease * More than 5 years since prior radiotherapy to any portion of the abdominal cavity or pelvis, except for the treatment of ovarian, fallopian tube, or primary peritoneal cancer * Prior radiotherapy for localized cancer of the breast, head and neck, or skin allowed, provided it was completed more than 3 years prior to study, and the patient remains free of recurrent or metastatic disease * No prior radiation to more than 25% of marrow-bearing areas * More than 28 days since prior radiotherapy * No other concurrent investigational or commercial agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years | From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Disease assessment for responses were performed every 6 weeks for as long as the patient remained on protocol treatment, up to 5 years. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR in conjunction with measured CA125 responses |
| Overall Survival | every 3 months for two years and then every 6 months for 3 years | From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. |
| Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Toxicity assessment was evaluated before each treatment cycle (21 days), up to 5 years. | Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. |
| Time to Treatment Failure | Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years. | Time to treatment failure after treatment with single agent vandetanib following progression on single agent docetaxel. Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years. |
| Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel | Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR in conjunction with measured CA125 responses |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I: Docetaxel Patients receive docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who progress also receive oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of a second disease progression or unacceptable toxicity.
docetaxel: Given IV
vandetanib: Given orally | 66 |
| Arm II: Docetaxel + Vandetanib Patients receive docetaxel IV over 1 hour on day 1 and oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
docetaxel: Given IV
vandetanib: Given orally | 63 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 15 |
| Overall Study | Not protocol specified | 3 | 8 |
| Overall Study | Progression/relapse | 47 | 35 |
| Overall Study | Withdrawal by Subject | 8 | 5 |
Baseline characteristics
| Characteristic | Arm I: Docetaxel | Arm II: Docetaxel + Vandetanib | Total |
|---|---|---|---|
| Age, Continuous | 61.7 years | 61.9 years | 61.9 years |
| Baseline serum level of cancer-antigen 125 (CA-125) ≤ 35 units/mL | 17 participants | 10 participants | 27 participants |
| Baseline serum level of cancer-antigen 125 (CA-125) > 35 units/mL | 49 participants | 53 participants | 102 participants |
| Gender Female | 66 Participants | 63 Participants | 129 Participants |
| Gender Male | 0 Participants | 0 Participants | 0 Participants |
| Hispanic No | 64 participants | 58 participants | 122 participants |
| Hispanic Unknown | 0 participants | 1 participants | 1 participants |
| Hispanic Yes | 2 participants | 4 participants | 6 participants |
| Performance Status 0 | 37 participants | 33 participants | 70 participants |
| Performance Status 1 | 27 participants | 26 participants | 53 participants |
| Performance Status 2 | 2 participants | 4 participants | 6 participants |
| Primary Site Fallopian Tube | 3 participants | 4 participants | 7 participants |
| Primary Site Ovary | 56 participants | 53 participants | 109 participants |
| Primary Site Peritoneal | 7 participants | 6 participants | 13 participants |
| Prior Antiangiogenic Therapy No | 54 participants | 54 participants | 108 participants |
| Prior Antiangiogenic Therapy Yes | 12 participants | 9 participants | 21 participants |
| Prior treatment with platinum for recurrent disease | 34 participants | 28 participants | 62 participants |
| Race/Ethnicity, Customized Asian | 4 participants | 2 participants | 6 participants |
| Race/Ethnicity, Customized Black | 4 participants | 4 participants | 8 participants |
| Race/Ethnicity, Customized Unknown | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 58 participants | 56 participants | 114 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 61 / 64 | 59 / 61 | 32 / 33 |
| serious Total, serious adverse events | 1 / 64 | 31 / 61 | 7 / 33 |
Outcome results
Primary
Progression Free Survival (PFS)
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.
Time frame: Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I: Docetaxel | Progression Free Survival (PFS) | 3.5 months |
| Arm II: Docetaxel + Vandetanib | Progression Free Survival (PFS) | 3.0 months |
p-value: 0.4980% CI: [0.79, 1.26]Regression, Cox
Secondary
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR in conjunction with measured CA125 responses
Time frame: Disease assessment for responses were performed every 6 weeks for as long as the patient remained on protocol treatment, up to 5 years.
Population: Analysis of response is in the subset of patients who had at least one measurable target lesion at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Complete Response | 0 participants |
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Partial Response | 5 participants |
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Unconfirmed Complete Response | 1 participants |
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Unconfirmed Partial Response | 2 participants |
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Stable/No Response | 19 participants |
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Increasing Disease | 23 participants |
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Symptomatic Deterioration | 0 participants |
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Assessment Inadequate | 7 participants |
| Arm II: Docetaxel + Vandetanib | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Assessment Inadequate | 6 participants |
| Arm II: Docetaxel + Vandetanib | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Complete Response | 0 participants |
| Arm II: Docetaxel + Vandetanib | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Stable/No Response | 17 participants |
| Arm II: Docetaxel + Vandetanib | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Partial Response | 6 participants |
| Arm II: Docetaxel + Vandetanib | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Symptomatic Deterioration | 1 participants |
| Arm II: Docetaxel + Vandetanib | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Unconfirmed Complete Response | 0 participants |
| Arm II: Docetaxel + Vandetanib | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Increasing Disease | 20 participants |
| Arm II: Docetaxel + Vandetanib | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease | Unconfirmed Partial Response | 2 participants |
Secondary
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR in conjunction with measured CA125 responses
Time frame: Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years.
Population: Analysis of response is in the subset of patients who had at least one measurable target lesion at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel | Complete Response | 0 participants |
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel | Partial Response | 0 participants |
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel | Unconfirmed Complete Response | 0 participants |
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel | Unconfirmed Partial Response | 1 participants |
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel | Stable/No Response | 8 participants |
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel | Increasing Disease | 20 participants |
| Arm I: Docetaxel | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel | Assessment Inadequate | 1 participants |
Secondary
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Toxicity assessment was evaluated before each treatment cycle (21 days), up to 5 years.
Population: Eligible patients who had received the protocol treatments were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (serious), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Edema limbs | 1 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Allergic reaction | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 1 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 1 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ascites | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bladder infection | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Chest pain - cardiac | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constipation | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 3 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Depression | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 2 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 6 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal pain | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 1 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypercalcemia | 1 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 1 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypocalcemia | 2 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 1 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypomagnesemia | 1 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 1 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 1 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 1 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 2 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 1 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nail infection | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 5 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 32 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Palmar-plantar erythrodysesthesia syndrome | 1 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Papulopustular rash | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 3 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pneumonitis | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pruritus | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash acneiform | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sinus bradycardia | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin and subcutaneous tissue disorders - Other | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Stoma site infection | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Treatment related secondary malignancy | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urinary tract infection | 0 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 3 Participants |
| Arm I: Docetaxel | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 20 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Treatment related secondary malignancy | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypercalcemia | 0 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pruritus | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 0 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypocalcemia | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash acneiform | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypomagnesemia | 2 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 0 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 4 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 0 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urinary tract infection | 2 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sinus bradycardia | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 0 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin and subcutaneous tissue disorders - Other | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 0 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nail infection | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 20 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 2 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Stoma site infection | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 28 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Allergic reaction | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 2 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Palmar-plantar erythrodysesthesia syndrome | 0 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 2 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ascites | 0 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 3 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bladder infection | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Papulopustular rash | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Chest pain - cardiac | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constipation | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 3 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 0 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Depression | 0 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 5 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 2 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Edema limbs | 0 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 5 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pneumonitis | 1 Participants |
| Arm II: Docetaxel + Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal pain | 1 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypercalcemia | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 1 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pruritus | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Allergic reaction | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 2 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Treatment related secondary malignancy | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Stoma site infection | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypocalcemia | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Depression | 1 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 1 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash acneiform | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypomagnesemia | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 1 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 1 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Palmar-plantar erythrodysesthesia syndrome | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 1 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ascites | 1 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal pain | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bladder infection | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sinus bradycardia | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 1 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urinary tract infection | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Chest pain - cardiac | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Papulopustular rash | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 1 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin and subcutaneous tissue disorders - Other | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pneumonitis | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nail infection | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constipation | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Edema limbs | 0 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 1 Participants |
| Vandetanib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 0 Participants |
Secondary
Overall Survival
From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time frame: every 3 months for two years and then every 6 months for 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I: Docetaxel | Overall Survival | 18 months |
| Arm II: Docetaxel + Vandetanib | Overall Survival | 14 months |
p-value: 0.8380% CI: [0.93, 1.68]Regression, Cox
Secondary
Time to Treatment Failure
Time to treatment failure after treatment with single agent vandetanib following progression on single agent docetaxel. Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years.
Time frame: Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I: Docetaxel | Time to Treatment Failure | 1.4 Months |