Clinical trial for assessment of safety and the efficacy of the combination of topotecan and pazopanib in patients with recurrent ovarian cancer

Phase 1

• Conditions: This study is a prospective single-arm, open-label, multicenterphase I/II trial. The phase I-trial is a dose-escalation trial todetermine the maxium tolerated dose (MTD) of pazopanib incombination with weekly topotean. The phase II-trial is a singlearm open-label trial to further assess the safety and the efficacy ofthis combination of treatment.; MedDRA version: 19.0Level: LLTClassification code 10033131Term: Ovarian carcinomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

• Registration Number: EUCTR2011-000259-17-DE
• Lead Sponsor: Charité - Universitätsmedizin Berlin

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12-07
• Last Update Posted: 1 October 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 68

Inclusion Criteria

1. Patients 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
assessments and procedures.
2. Histologically confirmed diagnosis of epithelian ovarian
cancer, primary peritoneal carcinoma or fallopian tube
cancer.
3. Patients must have platinum resistant (recurrence within 6
months of a platinum-containing regimen) or platinum
refractory (progression during platinum treatment) or
intermediate platinum-sensitive (recurrence within 12
months after a platinum-based primary therapy) disease.
4. No more than 2 prior treatment regimens for epithelial
ovarian cancer
5. Age ³18 years
6. Eastern Cooperative Oncology Group (ECOG)
performance status of 0 or 1
7. Adequate organ function defined as in the table below.
8. There must be measurable disease or evaluable disease
according to RECIST criteria.
9. Able to swallow and retain oral medication.
10. A life expectancy of at least 12 weeks.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 48
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

11. Prior malignancies; subject who have had another
malignancy and have been disease-free for 5 years which
effect progression free survival, or subject with a history of
completely resected non-melanomatous skin carcinoma or
successfully treated in situ carcinoma are eligible
12. 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.
13. Clinically significant gastrointestinal abnormalities that
might interfere with oral dosing or that may increase the
risk for gastrointestinal bleeding including, but not limited
to:
Active peptic ulcer disease
Known intraluminal metastatic lesion/s with suspected
bleeding
Inflammatory bowel disease (e.g. ulcerative colitis,
Crohn’s disease), or other gastrointestinal conditions
with increased risk of perforation
History of abdominal fistula, gastrointestinal perforation,
or intra-abdominal abscess within 28 days prior to
beginning study treatment
14. 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
15. Grade 3 or 4 diarrhoea
16. Any unstable or serious concurrent condition (e.g., active
infection requiring systemic therapy).
17. Poorly controlled hypertension [defined as systolic blood
pressure (SBP) of =140 mmHg or diastolic blood pressure
(DBP) of = 90mmHg].
Note: Initiation or adjustment of antihypertensive medication(s) is
permitted prior to study entry. BP must be re-assessed on two
occasions that are separated by a minimum of 1 hour; on each of
these occasions, the mean (of 3 readings) SBP / DBP values
from each BP assessment must be <140/90 mmHg in order for a
subject to be eligible for the study
18. Prolongation of corrected QT interval (QTc) >480 msecs
using Bazett’s formula.
19. History of any one or more of the following cardiovascular conditions within the past 6 months:
Cardiac angioplasty or stenting
Myocardial infarction
Unstable angina
Symptomatic peripheral vascular disease
Coronary artery by-pass graft surgery
20. Class III or IV congestive heart failure as defined by the
New York Heart Association (NYHA)
21. 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-coagulant agents (excluding therapeutic
warfarin) for at least 6 weeks are eligible.
22. Macroscopic hematuria
23. Hemoptysis in excess of 2.5 mL (or one half teaspoon)
within 8 weeks of first dose of study drug.
24. Evidence of active bleeding or bleeding diathesis.
25. Known endobronchial lesions and/or lesions infiltrating
major pulmonary vessels and/or involvement of large
pulmonary vessels by tumor
26. Prior major surgery or trauma within 14 days prior to first
dose of study drug and/or presence of any non-healing
wound, fracture, or ulcer.
27. Chemotherapy or radiation therapy or tumour embolization
within 2 weeks prior to the first d

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Phase I:<br>Determination of the maximal tolerable dosis (MTD) of the<br>combination of pazopanib and weekly topotecan<br>Phase II:<br>Determination of efficacy and safety of pazopanib and weekly<br>topotecan;Secondary Objective: · Overall survival<br>· Response rate (CR, PR) according to RECIST criteria<br>· Clinical benefit rate (CR, PR, SD)<br>· Duration of response<br>· Time to progression (TTP)<br>· Evaluation of CA-125 tumour response<br>· Safety and tolerability<br>· Quality of life as defined;Primary end point(s): Phase I: Dose-limiting toxicity<br>Phase II: Progression-free survival according to RECIST<br>criteria<br>;Timepoint(s) of evaluation of this end point: 12 months from end of topotecan treatment onwards

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): · Overall survival<br>· Response rate (CR, PR) according to RECIST criteria<br>· Clinical benefit rate (CR, PR, SD)<br>· Duration of response<br>· Time to progression (TTP)<br>· Evaluation of CA-125 tumour response<br>· Safety and tolerability<br>· Quality of life as defined by EORTC-QLQ C 30 and Ovar<br>28 questionnaire;Timepoint(s) of evaluation of this end point: 12 months from end of topotecan treatment onwards