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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief 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 Summary:

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
Sponsor: NHS Greater Glasgow and Clyde

Current Primary Outcome: Progression Free Survival (PFS) [ Time Frame: from date of randomisation to date of progression or death, which ever occurs earlier. Assessed up to 5 years 3 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Overall Survival [ Time Frame: defined as the number of days from date of randomisation to date of death (irrespective of reason). Assessed up to 5 years 3 months ]
  To estimate overall survival in women with relapsed clear cell carcinoma of the ovary, peritoneum or fallopian tube treated with Nintedanib and compare this to OS in women treated with chemotherapy.
• Disease control rate [ Time Frame: 12 weeks ]
  Disease control rate (Complete response, partial response and stable disease) at 12 weeks
• Quality of Life (QoL) [ Time Frame: up to 5 years ]
  Measured by EORTC QLQ C30 (EORTC Quality of Life Questionnaire Core 30) questionnaire. To assess quality of life in women with relapsed clear cell carcinoma of the ovary, peritoneum or fallopian tube and endometrium treated with Nintedanib and compare this to women treated with chemotherapy.
• Quality of Life (QoL) [ Time Frame: up to 5 years ]
  Measured by EORTC OV28 (Ovarian Cancer Module) questionnaire. To assess quality of life in women with relapsed clear cell carcinoma of the ovary, peritoneum or fallopian tube and endometrium treated with Nintedanib and compare this to women treated with chemotherapy.
• Quality of Life - recent symptoms of disease and treatment [ Time Frame: up to 5 years ]
  Measured by (Measure of Ovarian Cancer Symptoms and Treatment Concerns) MOST - Recent questionnaire. To measure recent symptoms of disease and treatment in women with relapsed clear cell carcinoma of the ovary, peritoneum or fallopian tube and endometrium treated with Nintedanib and compare this to women treated with chemotherapy.
• Q-TWIST (Quality-Adjusted Time Without Symptoms of Disease or Toxicity of Treatment) [ Time Frame: up to 5 years ]
  Measured by EuroQol Group questionnaire EQ-5D. Q-TWiST (Quality-Adjusted Time Without Symptoms of Disease or Toxicity of Treatment) will balance quality and quantity of time by combining survival data with EQ-5D quality of life data. Periods of time spent in ill health due to treatment toxicity or disease symptoms are weighted by average EQ-5D to give a quality of life adjusted time which is combined with a similarly adjusted time spent without either toxicity or symptoms
• Response Rate [ Time Frame: up to 2 years ]
  To estimate response rate (RR) in women with relapsed clear cell carcinoma of the endometrium treated with Nintedanib and those treated with chemotherapy. Best response rate will be determined according to a combined GCIG criteria and RECIST criteria Version 1.1
• Toxicity [ Time Frame: median 12 months ]
  Adverse event data will be collected during the treatment phase of the study. This will be coded and graded as per NCI-CTCAE v4.0. At the end of treatment, all patients presenting with grade 2 or above toxicities are assessed every 4 weeks until resolution of the toxicity or until another cancer treatment is administered.

Original Secondary Outcome: Same as current

Information By: NHS Greater Glasgow and Clyde

Dates:
Date Received: July 22, 2016
Date Started: April 2015
Date Completion: March 2021
Last Updated: August 10, 2016
Last Verified: July 2016