NCT02866370

Study Of Nintedanib Compared To Chemotherapy in Patients With Recurrent Clear Cell Carcinoma Of The Ovary Or Endometrium

A Randomised Phase II Study Of Nintedanib (BIBF1120) Compared To Chemotherapy in Patients With Recurrent Clear Cell Carcinoma Of The Ovary Or Endometrium

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: NHS Greater Glasgow and Clyde · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The trial will recruit up to 120 patients; 90 with ovarian clear cell carcinoma and up to 30 with endometrial clear cell carcinoma. Patients will be randomised between chemotherapy and Nintedanib 200mg twice daily oral administration (PO) continuously. The primary diagnosis must be histologically confirmed and central pathological review of the presenting tumour or biopsy of relapsed disease must find at least 50% clear cell carcinoma with no serous differentiation

Detailed description

Clear cell carcinoma (CCC) is an uncommon histotype of ovarian and a rare histotype of endometrial cancer. The prognosis for recurrent disease is poor with response rates to standard chemotherapy of \<10% so there is an urgent need for novel therapies. Ovarian CCC (OCCC) is biologically different from other ovarian cancer histotypes but shares features with renal CCC, including upregulation of angiogenesis pathways. Hence inhibition of angiogenesis, which has been a successful strategy in renal CCC, may also be of benefit in OCCC and endometrial CCC (ECCC). Nintedanib is a well-tolerated, potent, orally-available, kinase inhibitor targeting Vascular Endothelial Growth Factor (VEGFR) 1-3, Platelet Derived Growth Factor Receptor (PDGFR)α/β, and Firbroblas Gworth Factor Receptors (FGFR) 1-3. It is licensed in Europe in combination with docetaxel after first line chemotherapy for Non-Small Cell Lung Cancer (NSCLC). Importantly it also has significant activity as a single agent in renal CCC with an Overall Response Rate (ORR) of 20.3%, disease control rate of 76.% and 43% 9 month progression free survival. Response rates (RR) of ovarian CCC to standard chemotherapy with or without platinum are poor whatever line of treatment. A number of different agents are used in recurrent CCC and, although isolated instances of response to a variety of agents have been reported, no regimen seems to offer a particular advantage. As a result the investigators do not expect to see significant differences in response rates within the chemotherapy arms of the study. Hence it is feasible to allow physicians a choice of chemotherapy from a pre-specified selection and to include patients with multiple previous relapses. Since overall and progression free survival may be shorter with successive lines of treatment, the number of previous lines of treatment will be a stratification factor. These measures should maximise recruitment of this rare tumour sub-type across different countries.

Conditions

• Ovarian Clear Cell Carcinoma
• Endometrial Clear Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Nintedanib	Nintedanib (BIBF1120) 200mg twice daily PO, continuously, until progression or withdrawal from the treatment.
DRUG	Paclitaxel	Ovarian Cancer Patients Paclitaxel (80mg/m2) IV Day 1, 8, 15 every 28 days\* Endometrial Cancer Patients Carboplatin (AUC 5) and Paclitaxel (175mg/m2) IV every 21 days\* \* Patients will usually receive up to 6 cycles of chemotherapy. If in the opinion of the Investigator, a patient would benefit from continuing with chemotherapy beyond 6 cycles, it is acceptable to continue until progression or unacceptable toxicity.
DRUG	Pegylated Liposomal Doxorubicin (PLD)	Ovarian Cancer Patients Pegylated Liposomal Doxorubicin (PLD) (40mg/m2) IV every 28 days\* \* Patients will usually receive up to 6 cycles of chemotherapy. If in the opinion of the Investigator, a patient would benefit from continuing with chemotherapy beyond 6 cycles, it is acceptable to continue until progression or unacceptable toxicity. The maximal lifetime cumulative dose of doxorubicin or pegylated liposomal doxorubicin allowed is 450 mg/m2.
DRUG	Topotecan	Ovarian Cancer Patients Topotecan 4mg/m2 IV Day 1, 8, 15 every 28 days\* \* Patients will usually receive up to 6 cycles of chemotherapy. If in the opinion of the Investigator, a patient would benefit from continuing with chemotherapy beyond 6 cycles, it is acceptable to continue until progression or unacceptable toxicity.
DRUG	Carboplatin	Endometrial Cancer Patients Carboplatin (AUC 5) and Paclitaxel (175mg/m2) IV every 21 days\* \* Patients will usually receive up to 6 cycles of chemotherapy. If in the opinion of the Investigator, a patient would benefit from continuing with chemotherapy beyond 6 cycles, it is acceptable to continue until progression or unacceptable toxicity.
DRUG	Doxorubicin	Endometrial Cancer Patients Doxorubicin IV 60mg/m2 every 21 days\* \* Patients will usually receive up to 6 cycles of chemotherapy. If in the opinion of the Investigator, a patient would benefit from continuing with chemotherapy beyond 6 cycles, it is acceptable to continue until progression or unacceptable toxicity. The maximal lifetime cumulative dose of doxorubicin or pegylated liposomal doxorubicin allowed is 450 mg/m2.

Timeline

• Start date: 2015-04-01
• Primary completion: 2020-03-01
• Completion: 2021-03-01
• First posted: 2016-08-15
• Last updated: 2016-08-15

Locations

17 sites across 1 country: United Kingdom