To increase progression-free survival at 3 months.
ID
Source
Brief title
Condition
- Uterine, pelvic and broad ligament disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentage of patients free of progression at 3 months.
Secondary outcome
Response rate, progression free survival, overall survival,
tolerability/toxicity.
Background summary
Endometrial cancer is mainly diagnosed in the 6th and 7th decade of life, and
is often curable by surgery and/or radiotherapy. However, in the approximately
40% of patients with either recurrent or metastatic disease, survival is poor.
Although hormonal therapy with progestins is well tolerated, it yields a
response rate of only 15-30% overall. These responses occur almost exclusively
in well-differentiated, progesterone receptor-positive cancers which show a
response rate of 75%, vs. 7% in poorly differentiated tumors. Even
well-differentiated tumors become progestin resistant at some point. In hormone
resistant tumors, combination chemotherapy with
doxorubicin-cisplatin(-paclitaxel) leads to response rates of over 40%, but is
generally poorly tolerated in this elderly patient group. Median progression
free survival without treatment is 2 months, and with combination chemotherapy
4-8 months. Median overall survival does not exceed 12 months in most series,
with maximal OS reported in a randomized trial being 15 months using TAP.
Carboplatin-paclitaxel schedules, which are less toxic, are currently being
tested, but even this schedule is not always suitable for the endometrial
cancer population with frequent comorbidities. There is therefore a pressing
need for effective systemic treatment with an acceptable toxicity profile for
this patient group.
Angiogenesis inhibition is a novel cancer treatment that has proven efficacy in
a variety of tumors, such as colorectal cancer, breast cancer and lung cancer.
Angiogenesis plays an important part in the progression of endometrial cancer.
VEGF levels in endometrium cancer correlate with established poor prognostic
factors, and VEGF-A is overexpressed in endometrial cancer but not in benign
endometrial hyperplasia. The oral small molecule tyrosine kinase inhibitor
(TKI) pazopanib targets the ATP-binding site of the VEGF receptor (in addition
to the PDGHF and c-kit receptors). There is evidence of single agent activity
of pazopanib against renal cell cancer, ovarian cancer and sarcomas. Pazopanib
is well tolerated. The main side-effects are hypertension, fatigue and
gastro-intestinal symptoms. In view of the importance of angiogenesis in the
sustenance of endometrial cancer, pazopanib is an ideal candidate to study in
this disease.
Study objective
To increase progression-free survival at 3 months.
Study design
Multi-center open label non-randomized phase II study.
Intervention
Pazopanib 800 mg once daily PO.
Study burden and risks
Patients will visit the outpatient clinic at regular intervals, every 3 weeks
for the first 12 weeks, every 4 weeks for the next 12 weeks, and every 6 weeks
thereafter. At every visit blood will be drawn. Tumor assessment will take
place regularly, every 6 weeks for the first 12 weeks, and every 12 weeks
thereafter, for as long as patients continue study treatment. This is in
essence not differemnt from the evaluations that would be considered standard
in this patient group outside the realm of a study.
All patients will be exposed to pazopanib and therefore all may encounter
side-effects. Serious side-effects are fortunately rare. The main side-effects
are hypertension, fatigue and gastro-intestinal symptoms.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
1. Written informed consent.
2. Age * 18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
4. Histologically or cytologically confirmed diagnosis of endometrial cancer.
5. Metastatic disease or locally advanced tumor not amenable to local therapy.
6. Documented progressive disease before enrolment.
7. Measurable lesions outside irradiated field or progressive measurable lesions in irradiated area.
8. Not eligible for hormonal therapy (because of negative hormone receptor/poor differentiation, or after failure of hormonal therapy)
9. Previous failure of chemotherapy, or refusal to undergo chemotherapy or chemo-naive patients not suitable for chemotherapy.
10. Adequate organ system function
Exclusion criteria
1. Prior malignancy.
Note: Subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
2. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, with no radiological signs of progression and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug.
3. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding or may affect absorption of investigational product.
4. Presence of uncontrolled infection.
5. Corrected QT interval (QTc) > 480 msecs using Bazett*s formula
6. History of major cardiovascular conditions within the past 6 months or poorly controlled hypertension, 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.
7. 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).
8. Evidence of active bleeding or bleeding diathesis.
9. 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-000287-99-NL |
| CCMO | NL35873.018.11 |