| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
This study is a prospective single-arm, open-label, multicenter
phase I/II trial. The phase I-trial is a dose-escalation trial to
determine the maxium tolerated dose (MTD) of pazopanib in
combination with weekly topotean. The phase II-trial is a single
arm open-label trial to further assess the safety and the efficacy of
this combination of treatment. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with recurrent ovarian cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10033131 |
| E.1.2 | Term | Ovarian carcinoma |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Phase I:
Determination of the maximal tolerable dosis (MTD) of the
combination of pazopanib and weekly topotecan
Phase II:
Determination of efficacy and safety of pazopanib and weekly
topotecan |
|
| E.2.2 | Secondary objectives of the trial |
· Overall survival
· Response rate (CR, PR) according to RECIST criteria
· Clinical benefit rate (CR, PR, SD)
· Duration of response
· Time to progression (TTP)
· Evaluation of CA-125 tumour response
· Safety and tolerability
· Quality of life as defined |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Associated Translational Project within the EUTROC - European Network of Translational Research in Ovarian Cancer (www.eutroc.org)
included in the study protocol V 1.1from 03.06.2011
The purpose of the sub-study is to identify new approaches to predicting treatment response and survival by examining biomarkers at the protein and RNA level. Such examinations may also be undertaken by scientific co-operation partners. These examinations therefore do not in any way restrict the histological diagnosis or the clinical management.These translational examinations are focused on predictive and prognostic molecular biological markers and will be submitted separately and in detail to the Ethics Committee. For the subsequent examinations, the necessary data will be stored anonymously. The purpose of the examinations is to be able to develop improved treatment plans in future. For this reason, the results of the experimental studies will not be notified to the attending doctors or patients as their significance is still largely unclear and no consequences can be drawn from them for the treatment or further care of patients. |
|
| E.3 | Principal 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. |
|
| E.4 | Principal 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 dose of study drug.
28. Biological therapy, immunotherapy, hormonal therapy or
treatment with an investigational agent within 14 days (for
bevacizumab, 60 days) or 5 half-lives, whichever is longer
prior to the first dose of study drug.
29. Is unable or unwilling to discontinue predefined prohibited
medications listed in the protocol for 14 days or five halflives
of a drug (whichever is longer) prior to first dose of
study drug and for the duration of the study
30. Any ongoing toxicity from prior anti-cancer therapy that is
>Grade 1 and/or that is progressing in severity, except
alopecia.
31. Known immediate or delayed hypersensitivity reaction or
idiosyncrasy to drugs chemically related to pazopanib
32. Psychological, familial, sociological, or geographical
conditions that do not permit compliance with the protocol.
33. Clinically assessed as having inadequate venous access
for PK sampling.
34. Any condition that is unstable or could jeopardize the
safety of the patient and their compliance in the study
35. Legal incapacity or limited legal capacity
36. Participation in another clinical study with experimental
therapy within the 30 days before start of treatment
37. Subjects housed in an institution on official or legal orders.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Phase I: Dose-limiting toxicity
Phase II: Progression-free survival according to RECIST
criteria
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 12 months from end of topotecan treatment onwards |
|
| E.5.2 | Secondary end point(s) |
· Overall survival
· Response rate (CR, PR) according to RECIST criteria
· Clinical benefit rate (CR, PR, SD)
· Duration of response
· Time to progression (TTP)
· Evaluation of CA-125 tumour response
· Safety and tolerability
· Quality of life as defined by EORTC-QLQ C 30 and Ovar
28 questionnaire |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 12 months from end of topotecan treatment onwards |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 2 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Last visit of the last subject |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
