Trial of PAZOpanib with or without FOSbretabulin in advanced recurrent ovarian cancer

Phase 1

Completed

• Conditions: Topic: Cancer; Subtopic: Gynaecological Cancer; Disease: Ovary/Fallopian tube; Cancer; Overlapping lesion of female genital organs

• Registration Number: ISRCTN30090285
• Lead Sponsor: The Christie NHS Foundation Trust (UK)

Brief Summary

2018 conference abstract in: https://doi.org/10.1093/annonc/mdy285.164

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-04-17
• Study Completion: 2017-03-31
• Last Update Posted: 5 May 2019

Recruitment & Eligibility

• Status: Completed
• Sex: Female
• Target Recruitment: 33

Inclusion Criteria

1. Advanced, progressive, recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma, which has recurred following at least one platinum-containing regimen.
2. Progressive disease according to RECIST 1.1 or GCIG criteria within 312 months of completing platinum-containing therapy, although this need not be the immediately preceding regimen.
3. World Health Organisation (WHO) performance status of 0 or 1 (Appendix 1).
4. Measurable disease (RECIST 1.1 (Appendix 2) or PD according to CA125 GCIG criteria with non-measurable disease on CT scan.
5. Life expectancy of at least 12 weeks.
6. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day 7 to Day 1) before the patient receives the first dose of IMP. Laboratory Test Value required:
6.1. Haemoglobin (Hb) = 90 g/L
6.2. Absolute neutrophil count = 1.5 x 10*9/L
6.3. Platelet count = 100 x 10*9/L
6.4. Serum potassium within normal range
6.5. Bilirubin up to 1.5 x ULN and
6.6. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) = 2.5 x ULN unless raised due to hepatic metastatic disease in which case up to 5 x ULN is permissible
6.7. Calculated creatinine clearance or isotope clearance measurement = 40 mL/min
6.8. Activated partial thromboplastin time (aPTT) = 1.2 x ULN
6.9. Prothrombin Time (PT) or international normalised ratio (INR) = 1.3 x ULN
7. Urine protein dipstick of less than 2+, or if 2+ or greater the patient must have a 24-hour urinary protein value of less than 2 g.
8. Clinically euthyroid
9. Aged 18 years or over at the time of consent
10. Written (signed and dated) informed consent and capable of cooperating with treatment and follow-up
11. Patients can have received bevacizumab prior to trial entry providing that the last dose was administered at least 6 months before the first dose of IMP
Target Gender: Female ; Lower Age Limit 18 years

Exclusion Criteria

1. Radiotherapy, surgery or tumour embolisation within 28 days before the first dose of IMP
2. Endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin C and six weeks for investigational medicinal products) before the first dose of IMP.
3. Ongoing grade = 2 toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Chief and Principal Investigators should not exclude the patient; and grade 1 or 2 neurotoxicity considered to be due to paclitaxel.
4. Female patients who are able to become pregnant (or are already pregnant or lactating). Those who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have an intrauterine device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for six months afterwards are considered eligible.
5. Major thoracic or abdominal surgery from which the patient has not yet recovered.
6. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
7. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
8. History of any of the following cardiovascular conditions within the last six months:
8.1. Coronary revascularisation (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG])
8.2. Acute coronary syndrome (myocardial infarction [MI], unstable angina)
8.3. Symptomatic peripheral vascular disease
8.4. Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) (Appendix 4)
9. Patients who have sustained hypertension, defined as a systolic blood pressure (SBP) of > 140 mmHg or diastolic blood pressure (DBP) of > 90 mmHg, on three occasions.
10. ECG with evidence of clinically significant abnormalities.
11. Patients with a QTc > 480 ms or taking any drug known to prolong the QTc interval that cannot be stopped for the duration of the trial (Appendix 4).
12. Patients with pathologic bradycardia (<60 b/m in nonathletes), heart block (excluding first-degree block, being PR interval prolongation only).
13. History of cerebrovascular accident (including transient ischaemic attack [TIA]), pulmonary embolism or untreated deep vein thrombosis (DVT) within the past six months. Patients with recent DVT who have been treated with therapeutic anticoagulant agents for at least six weeks will be eligible, provided their INR (if taking oral anticoagulants) has been stable for this period of time.
14. 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 anticonvulsant medication for six months prior to the first dose of IMP.
15. Clinically significant abnormalities that may increase the risk of gastrointestinal bleeding or perforation, including but not limited to:

Study & Design

• Study Type: Interventional
• Study Design: Not specified