Clinical Trial Investigating Pazopanib in Patients With Platinum-resistant Advanced Ovarian Cancer

• Status: Completed
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

Given the low Responses Rates and short survival times achieved with conventional cytotoxic agents in resistant ovarian cancer patients, new treatment options are needed in this patient population.Antiangiogenic therapy has an important role in this group of patients and Pazopanib in particular. We are going to study if Pazopanib is able to control disease-related symptoms minimizing the side effects of treatment. This aspect is very important in the treatment of resistant ovarian cancer patient since our treatment is palliative without any impact in overall survival. So our goal is to study the Clinical Benefit Rate (objective responses plus stable disease rates) achieved with Pazopanib and its toxicity profile in this subgroup of patients

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Grupo Español de Investigación en Cáncer de Ovario

Criteria

Inclusion Criteria:

1. Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up.

2. Age ≥ 18 years

3. The patient has histologically or cytologically confirmed epithelial ovarian cancer, primary peritoneal carcinoma, fallopian tube cancer

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

5. The patient has completed at least 4 CYCLES OF one and up to two platinum-containing regimens (involving cisplatin or carboplatin),for the management of this condition. Treatment may have included intraperitoneal therapy, consolidation or extended therapy administered after surgical or nonsurgical assessment.

6. The patient must have a platinum-free interval of ≤ 6 months after the final dose of primary or subsequent platinum-based therapy.

Patients must have platinum-resistant disease,(defined as progression within <6 months from completion of a minimum of 4 platinum therapy cycles. The date should be calculated from the last administered dose of platinum therapy.

7. The patient has at least one unidimensionally measurable target lesion (≥ 20 mm or ≥ 10 mm by spiral computed tomography [CT] or magnetic resonance imaging [MRI]), as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines V 1.1.

8. Previously archived tumor tissue from either the primary or metastatic tumor (paraffin block or 10 unstained slides) should be collected prior to administration of the first dose of study therapy and stored at a secure central laboratory.

9. Adequate organ system function

10. Women of child bearing potential should be using an effective method of contraception (complete abstinence, any intrauterine device (IUD) with published data showing that the lowest expected failure rate is < 1 % per year; or any other methods with published data showing that the lowest expected failure rate is less than 1 % per year) before entry into the study and throughout the same and for 6 months after ending the study. Women of childbearing potential must have a negative test serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta human chorionic gonadotropin [β-HCG]) within 7 days prior to randomization.

11. Able to swallow oral compound.

12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.

Exclusion Criteria:

1. Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.

2. Previous treatment with >2 anticancer regimens for ovarian cancer

3. Prior treatment with any antiangiogenic treatment (i.e. Bevacizumab)

4. Patients with platinum-refractory disease defined as those patients progress during platinum-based therapy.

5. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases.

6. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:

• Active peptic ulcer disease

• Known intraluminal metastatic lesion/s with risk of bleeding

• Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease), or other gastrointestinal conditions with increased risk of perforation

• History of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment.

• active episodes of intestinal pseudo-obstruction

7. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:

• Malabsorption syndrome

• Major resection of the stomach or small bowel.

• Grade 3 diarrhoea

8. Presence of uncontrolled infection.

9. Corrected QT interval (QTc) > 480 msecs using Bazett's formula

10. History of any one or more of the following cardiovascular conditions within the past 6 months:

• Cardiac angioplasty or stenting

• Myocardial infarction

• Unstable angina

• Coronary artery bypass graft surgery

• Symptomatic peripheral vascular disease

• Class II, III or IV congestive heart failure, as defined by the New York Heart Association (NYHA

11. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg] instead an anti-hypertensive treatment.

Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be assessed using the following recommendations:

Once a patient has had an elevated blood pressure reading (> 140/80mmHg) this should be confirmed with another measurement, done locally if possible, either by the patients local doctor, or by home monitoring if available. Patients should continue to have their blood pressure monitored, at least weekly, until it becomes controlled (i.e. ≤ 140/80mmHg on 2 separate occasions, at least one week apart). Anti-hypertension medication changes, such as initiation of therapy, dose increases of existing therapies, or addition of other anti-hypertensive agents, should be done if the blood pressure remains high at 2 consecutive readings, at least 24 hours apart. Please, refer to guidance regarding the management of hypertension for the patient's local doctor for further information.

12. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.

Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible

13. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).

14. Prior minor surgery within 7 days prior to first dose of study drug

15. Evidence of active bleeding or bleeding diathesis.

16. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

17. Hemoptysis within 6 weeks of first dose of study drug.

18. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.

19. Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.

20. Treatment with any of the following anti-cancer therapies:

radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib

21. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.

22. Women who are pregnant or breast-feeding