| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced Ovarian Cancer (FIGO Stage II, Stage III, and Stage IV epithelial ovarian, fallopian tube, or primary peritoneal cancer). |
|
| E.1.1.1 | Medical condition in easily understood language |
| Advanced Ovarian Cancer (FIGO Stage II, Stage III, and Stage IV epithelial ovarian, fallopian tube, or primary peritoneal cancer). |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10033128 |
| E.1.2 | Term | Ovarian cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
To determine whether pazopanib (52 weeks of pazopanib 800 mg daily) prolongs progression free survival (PFS)
in women with non-bulky, FIGO Stage II-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer that
has not progressed after first line chemotherapy. |
|
| E.2.2 | Secondary objectives of the trial |
To compare the effect of 52 weeks of pazopanib 800 mg daily versus placebo on
- Overall survival (key secondary endpoint)
- Safety
- PFS by GCIG criteria
- 3-year PFS rate
- Quality of life (measured using EORTC QLQ-C30 with the OV-28 module, and
EuroQOL EQ-5D). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A subject will be considered eligible for inclusion in this study if all the following criteria are met:
1. Subject has provided written informed consent prior to performance of study-specific procedures or assessments, and is willing to comply with treatment and follow-up. Note: Procedures conducted as part of the subject’s routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes
provided these procedures meet the protocol requirements.
2. Subject is >= 18 years old.
3. Subject has histologically confirmed, FIGO stage II-IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma that was treated with surgical debulking and at least five cycles of platinum-taxane doublet chemotherapy. Note: Intravenous, intraperitoneal, or neoadjuvant platinum-taxane doublet chemotherapy are
allowed; for weekly therapy, three weeks are considered one cycle. Interval debulking is allowed; second look is also allowed, as long as neither procedure is related to, or indicate, disease progression.
4. The date of study randomization must be at least 3 weeks and not more than 12 weeks from the date of the last chemotherapy dose, and all major toxicities from the previous chemotherapy must have resolved to grade 1 or better.
5. Subject has had no evidence of disease progression throughout their first-line treatment and prior to study randomization, including -CT or MRI scan taken within 6 weeks prior to randomization showing no radiological progression, and -CA-125 measurement taken within 6 weeks prior to randomization showing no CA-125 progression (according to the GCIG criteria, Appendix 2), and - no other clinical evidence of disease progression.
6. Subject has ECOG status of 0 - 2.
7. Subject is able to swallow and retain oral medication.
8. Subject has adequate hematologic, hepatic, and renal system function as defined in the protocol.
9. Subject is of:
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has
had:
•A hysterectomy
•A bilateral oophorectomy (ovariectomy)
•A bilateral tubal ligation
•Is post-menopausal.
Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for ≥ 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >40 mIU/mL and an estradiol value < 40pg/mL (<140 pmol/L).
Subjects who are using HRT and whose menopausal status is in doubt will be required to use a highly effective
method of contraception (outlined below) if they wish to continue with their HRT during the study. Otherwise, these subjects must discontinue HRT prior to study enrollment to allow confirmation of post-menopausal status. For most forms of HRT, at least 2-4 weeks must elapse between the cessation of HRT and determination of menopausal status; length of this interval depends on the type and dosage of HRT. If a female subject is
determined not to be post-menopausal, they must use adequate contraception, as defined immediately below.
OR
Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate
contraception. GSK acceptable contraceptive methods, when used consistently and in accordance with both the
product label and the instructions of the physician, are as follows:
•An intrauterine device with a documented failure rate of less than 1% per year.
•Vasectomized partner who is sterile prior to the female subject’s entry and is the sole sexual partner for that female.
•Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product.
•Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with
spermicide; or male condom and diaphragm with spermicide).
Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to, or a
beneficiary of, a social security category. |
|
| E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Subject has either (a) bulky disease (eg, ascites that causes abdominal distention or requires paracentesis; mesenteric thickening; or tumor masses of 2 cm or more by CT or MRI identified on the baseline scan), or (b) any residual disease which in the opinion of the investigator will need imminent second-line therapy
2. Subjects with synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless ALL of the following criteria for describing the endometrial carcinoma are met
- FIGO Stage <= IB, and
- No lymphovascular invasion, and
- Not poorly differentiated (i.e. not Grade 3 or papillary serous or clear cell)
3. Subject has clinically significant gastrointestinal abnormalities including, but not limited to:
- Malabsorption syndrome
- Major resection of the stomach or small bowel that could affect the absorption of study drug (eg, short bowel syndrome)
- Active peptic ulcer disease
- Known intraluminal metastatic lesion/s with suspected bleeding
- Inflammatory bowel disease
- Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess.
4. Subject has prolongation of corrected QT interval (QTc) > 480 msecs in the Screening ECG.
5. Subject has a history of any one or more of the following cardiovascular conditions within the past 6 months prior to randomization:
- Cardiac angioplasty or stenting
- Myocardial infarction
- Unstable angina
- Symptomatic peripheral vascular disease
- Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
6. Subject has poorly controlled hypertension [defined as systolic blood pressure (SBP) of >=140mmHg or diastolic blood pressure (DBP) of >= 90mmHg].
Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. At Screening, blood pressure must be assessed on at least two occasions that are separated by a minimum of 24 hours. The mean SBP / DBP values from each blood pressure assessment must be <140/90mmHg in order for a subject to be eligible for the study.
7. Subject has a history of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months prior to randomization.
Note: Subjects with recent DVT who have been treated with therapeutic anticoagulating agents for at least 6 weeks are eligible.
8. Subject has had major surgery (including interval debulking) or trauma within 28 days, or minor surgical procedures (eg, central venous access line removal) within 7 days, prior to randomization, or has any non-healing wound, fracture, or ulcer.
9. Subject has evidence of active bleeding or bleeding diathesis.
10. Subject has had hemoptysis within 6 weeks prior to randomization.
11. Subject has known endobronchial metastases.
12. Subject has any serious and/or unstable pre-existing medical (e.g., uncontrolled infection), psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
13. Subject has been administered an investigational or anti-VEGF anticancer therapy prior to study randomization. Schedule, route, and dose variations of registered drugs do not account for investigational drugs.
14. Subject has known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib.
15. Subject has prior or concurrent invasive malignancies that currently or within the last 5 years show/ed activity of disease (except ovarian, fallopian tube, or peritoneal cancer, or concurrent endometrial cancer FIGO stages IA/B as described above). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint for this study is PFS, defined as the interval between the date of
randomization and the date of radiological disease progression (by RECIST criteria) or death due to any cause. |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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) | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| 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 | Yes |
| E.8.2.3 | Other | No |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 350 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| China |
| Hong Kong |
| Japan |
| Korea, Republic of |
| Taiwan |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| All subjects will receive up to 52 weeks (12 months) of investigational product, after which, depending on their disease progression status, they will enter a Post-treatment observation period or a survival Follow-up Period as defined in the protocol. Following the final analyses of all primary and secondary endpoints, the study will conclude. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| 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 | 6 |
| 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 |
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