Ovarian Clear Cell CarcinomaPhase 2NiCCCNCT02866370
Study Of Nintedanib Compared To Chemotherapy in Patients With Recurrent Clear Cell Carcinoma Of The Ovary Or Endometrium
A Phase 2 study testing Nintedanib, Paclitaxel and Pegylated Liposomal Doxorubicin (PLD) in people with Ovarian Clear Cell Carcinoma and Endometrial Clear Cell Carcinoma, run by NHS Greater Glasgow and Clyde at 17 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Clear Cell Carcinoma, Endometrial Clear Cell Carcinoma
- What is being tested?
- Nintedanib, Paclitaxel and Pegylated Liposomal Doxorubicin (PLD)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 17 sitesUnited Kingdom
- Study dates
- Apr 2015to Mar 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Progressive or recurrent ovarian peritoneal or fallopian tube clear cell carcinoma, or progressive or recurrent endometrial clear cell carcinoma. 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. Progressive disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
- Failure after ≥1 prior platinum containing regimen which may have been given in the adjuvant setting. For patients with ovarian clear cell carcinoma, progression must have occurred within 6 calendar months of their last platinum dose.
- ECOG (Eastern Cooperative Oncology Group) Performance status of ≤2.
- Life expectancy of >3 months.
- Adequate hepatic, bone marrow coagulation and renal function
- Hepatic function: total bilirubin < Upper Limit of Normal (ULN); ALT and AST < 2.5 x ULN
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- Coagulation parameters: INR (International Normalised Ratio) <2 x ULN and prothrombin time and activated partial thromboplastin time < 1.5 x ULN in the absence of therapeutic anticoagulation
- absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- platelets ≥ 100 x 109L
- haemoglobin ≥ 9.0 g/dL
- proteinuria < grade 2 CTCAE (version 4)
- Glomerular Filtration Rate ≥40ml/min. (calculated using the Wright, Cockroft \& Gault equation or measured by EDTA clearance)
- Female and > 18 years of age.
- Signed and dated written informed consent prior to admission to the study in accordance with International Conference on Harmonization on Good Clinical Practice (ICH-GCP) guidelines and local legislation.
- Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures.
Who cannot join
- Prior treatment with Nintedanib or other angiogenesis inhibitor/VEGF targeted therapy, except for prior treatment with bevacizumab which is permitted.
- Treatment within 28 days prior to randomisation with any investigational drug, radiotherapy, immunotherapy, chemotherapy, hormonal therapy or biological therapy. Palliative radiotherapy may be permitted for symptomatic control of pain from bone metastases in extremities, provided that the radiotherapy does not affect target lesions, and the reason for the radiotherapy does not reflect progressive disease.
- Previous treatment with the chemotherapy regimen selected as the control arm by the investigator. (Prior therapy with paclitaxel given on a three weekly regimen is permitted for patients receiving weekly paclitaxel. Prior treatment with weekly paclitaxel is permitted where this has been used as part of first line therapy and it is greater than 6 months since the last dose of weekly paclitaxel. Prior weekly paclitaxel for relapsed disease is not permitted).
- Other malignancy diagnosed within 5 years of enrolment except for:
- non-melanomatous skin cancer (if adequately treated)
- cervical carcinoma in situ (if adequately treated)
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- carcinoma in situ of the breast (if adequately treated)
- For patients with ovarian clear cell cancer, prior or synchronous endometrial cancer (if adequately treated), provided all of the following criteria are met:
- disease stage FIGO (International Federation of Gynecology and Obstetrics) Stage 1a (tumour invades less than one half of myometrium)
- Grade 1 or 2
- Patients with any other severe concurrent disease, which may increase the risk associated with study participation or study drug administration and, in the judgement of the investigator, would make the patient inappropriate for entry into this study, including significant neurologic, psychiatric, infectious, hepatic, renal, or gastrointestinal diseases or laboratory abnormality.
- Symptoms or signs of gastrointestinal obstruction requiring parenteral nutrition or hydration or any other gastro-intestinal disorders or abnormalities, including difficulty swallowing, that would interfere with drug absorption.
- Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal) or antiviral therapy, including known hepatitis B and/or C infection and HIV-infection.
- Symptomatic central nervous system (CNS) metastasis or leptomeningeal carcinomatosis.
- Known, uncontrolled hypersensitivity to the investigational drugs or their excipients.
- Hypersensitivity to Nintedanib, peanut or soya, or to any of the excipients of Nintedanib.
- Significant cardiovascular diseases, including uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months prior to randomisation, congestive heart failure > NYHA (New York Heart Association) III, severe peripheral vascular disease, clinically significant pericardial effusion.
- History of major thromboembolic event, such as pulmonary embolism or proximal deep vein thrombosis, unless on stable therapeutic anticoagulation
- Known inherited predisposition to bleeding or thrombosis.
- History of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 6 months.
- History of clinically significant haemorrhage in the past 6 months.
- Major injuries or surgery within the past 28 days prior to start of study treatment or planned surgery during the on-treatment study period.
- Pregnancy or breastfeeding. Patients with preserved reproductive capacity must have a negative pregnancy test (β-HCG test in urine or serum) prior to commencing study treatment.
- Patients with preserved reproductive capacity, unwilling to use a medically acceptable method of contraception (see section 5.7) for the duration of the trial and for 6 months afterwards.
- Radiographic evidence of cavitating or necrotic tumours with invasion of adjacent major blood vessels.
- Any psychological, familial, sociological or geographical consideration potentially hampering compliance with the study protocol and follow up schedule; those considerations should be discussed with the patient before registration in the trial.
- Patients who have already received maximal lifetime dose of anthracycline or have experienced cardiac toxicity from an anthracycline should not receive doxorubicin or Paclitaxel Liposomal Doxorubicin (PLD).
Trial locations and contacts
17 sites in 1 country.
Claire A Lawless contact
17 sites in 1 country
United Kingdom17 sites, 17 recruiting
- Recruiting
Belfast City Hospital (Northern Ireland Cancer Centre)
Belfast
Sarah McKenna
- Recruiting
Bristol Heamatology and Cancer Centre
Bristol
Axel Walther
- Recruiting
Velindre Hospital
Cardiff
Rachel Jones
- Recruiting
Ninewells Hospital
Dundee, Tayside
Michelle Ferguson
- Recruiting
Beatson West of Scotland Cancer Centre
Glasgow, Lanarkshire, G12 0YN
Ros Glasspool
Ros Glasspool
- Recruiting
Kent & Canterbury Hospital
Kent
Justin Waters
- Recruiting
Queen Elizabeth Queen Mother Hospital
Kent
Justin Waters
- Recruiting
William Harvey Hospital
Kent
Justin Waters
- Recruiting
St James Hospital
Leeds
Geoff Hall
- Recruiting
Clatterbridge Cancer Centre
Liverpool, Wirral
Rosemary Lord
- Recruiting
Guy's Hosital
London
Ana Montes
- Recruiting
Royal Marsden Hospital
London
Susannah Bannerjee
- Not yet recruiting
St Bartholomew's Hospital
London
Melanie Powell
- Not yet recruiting
University College London Hospital
London
Jonathan Ledermann
- Recruiting
The Christie Hospital
Manchester
Andrew Clamp
- Recruiting
Great Western Hospital
Swindon
Omar Khan
- Recruiting
Musgrove Park Hospital
Taunton
Clare Barlow
About this study
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
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
Read the 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.
- Being tested
- Nintedanib, Paclitaxel, Pegylated Liposomal Doxorubicin (PLD), Topotecan, Carboplatin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NintedanibDrug
Also called BIBF 1120, Vargatef
Nintedanib (BIBF1120) 200mg twice daily PO, continuously, until progression or withdrawal from the treatment.
PaclitaxelDrug
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.
Pegylated Liposomal Doxorubicin (PLD)Drug
Also called Caelyx
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.
TopotecanDrug
Also called Hycamtin
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.
CarboplatinDrug
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.
DoxorubicinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Nintedanib | Experimental | Nintedanib (BIBF1120) 200mg twice daily PO, continuously Receives: Drug: Nintedanib |
| Chemotherapy | Active comparator | Ovarian Cancer Patients:
Paclitaxel (80mg/m2) IV Day 1, 8, 15 every 28 days Pegylated Liposomal Doxorubicin (PLD) (40mg/m2) IV every 28 days Topotecan (4mg/m2) IV Day 1, 8, 15 every 28 days
Endometrial Cancer Patients:
Carboplatin (AUC 5) and Paclitaxel (175mg/m2) IV every 21 days 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. Receives: Drug: Paclitaxel; Drug: Pegylated Liposomal Doxorubicin (PLD); Drug: Topotecan; Drug: Carboplatin; Drug: Doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
To estimate the progression free survival (PFS) in women with relapsed clear cell carcinoma of the ovary, peritoneum or fallopian tube treated with Nintedanib and compare this to PFS in women treated with chemotherapy.
Measured: from date of randomisation to date of progression or death, which ever occurs earlier. Assessed up to 5 years 3 months
Secondary outcomes (8)
Overall Survival
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.
Measured: defined as the number of days from date of randomisation to date of death (irrespective of reason). Assessed up to 5 years 3 months
Disease control rate
Disease control rate (Complete response, partial response and stable disease) at 12 weeks
Measured: 12 weeks
Quality of Life (QoL)
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.
Measured: up to 5 years
Quality of Life (QoL)
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.
Measured: up to 5 years
Quality of Life - recent symptoms of disease and treatment
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.
Measured: up to 5 years
Q-TWIST (Quality-Adjusted Time Without Symptoms of Disease or Toxicity of Treatment)
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
Measured: up to 5 years
Response Rate
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
Measured: up to 2 years
Toxicity
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.
Measured: median 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2016 (estimated)
- Study startApr 2015
- Primary completionMar 2020 (estimated)
- Study completionMar 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian Clear Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NHS Greater Glasgow and Clyde
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim, Cancer Research UK, European Organisation for Research and Treatment of Cancer - EORTC, Nordic Society of Gynaecological Oncology - Clinical Trials Unit, ARCAGY/ GINECO GROUP
- Responsible party
- Sponsor
- Investigators
- Rosalind Glasspool, Principal investigator, NHS Greater Glasgow and Clyde
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02866370
- Sponsor's protocol ID
- GN12ON259 (NiCCC2013)
- Other IDs
- 2013-002109-73, ISRCTN50772895, ENGOT-GYN1, EORTC1212
- Acronym
- NiCCC
- Status last verified
- Jul 2016
- First submitted
- 22 Jul 2016
- Last updated
- 15 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: It is proposed that data generated by the study will be available 2 years after completion of the trial, or after publication of the first major paper describing the dataset, whichever occurs sooner.
Publications
Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.
PubMed 37185961
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02866370
- Acronym / sponsor ID
- NiCCC / GN12ON259 (NiCCC2013)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- NHS Greater Glasgow and ClydeUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim, Cancer Research UK, European Organisation for Research and Treatment of Cancer - EORTC, Nordic Society of Gynaecological Oncology - Clinical Trials Unit, ARCAGY/ GINECO GROUP
- Study start
- Apr 2015
- Primary completion
- Mar 2020 (estimated)
- Study completion
- Mar 2021 (estimated)
- First posted
- 15 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nintedanib | Experimental | Drug: NintedanibNintedanib (BIBF1120) 200mg twice daily PO, continuously |
| Chemotherapy | Active comparator | Drug: Paclitaxel, Drug: Pegylated Liposomal Doxorubicin (PLD), Drug: Topotecan, Drug: Carboplatin, Drug: DoxorubicinOvarian Cancer Patients: Paclitaxel (80mg/m2) IV Day 1, 8, 15 every 28 days Pegylated Liposomal Doxorubicin (PLD) (40mg/m2) IV every 28 days Topotecan (4mg/m2) IV Day 1, 8, 15 every 28 days Endometrial Cancer Patients: Carboplatin (AUC 5) and Paclitaxel (175mg/m2) IV every 21 days 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Progressive or recurrent ovarian peritoneal or fallopian tube clear cell carcinoma, or progressive or recurrent endometrial clear cell carcinoma. 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. Progressive disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
- Failure after ≥1 prior platinum containing regimen which may have been given in the adjuvant setting. For patients with ovarian clear cell carcinoma, progression must have occurred within 6 calendar months of their last platinum dose.
- ECOG (Eastern Cooperative Oncology Group) Performance status of ≤2.
- Life expectancy of >3 months.
- Adequate hepatic, bone marrow coagulation and renal function
Key exclusion criteria (27 listed)
- Prior treatment with Nintedanib or other angiogenesis inhibitor/VEGF targeted therapy, except for prior treatment with bevacizumab which is permitted.
- Treatment within 28 days prior to randomisation with any investigational drug, radiotherapy, immunotherapy, chemotherapy, hormonal therapy or biological therapy. Palliative radiotherapy may be permitted for symptomatic control of pain from bone metastases in extremities, provided that the radiotherapy does not affect target lesions, and the reason for the radiotherapy does not reflect progressive disease.
- Previous treatment with the chemotherapy regimen selected as the control arm by the investigator. (Prior therapy with paclitaxel given on a three weekly regimen is permitted for patients receiving weekly paclitaxel. Prior treatment with weekly paclitaxel is permitted where this has been used as part of first line therapy and it is greater than 6 months since the last dose of weekly paclitaxel. Prior weekly paclitaxel for relapsed disease is not permitted).
- Other malignancy diagnosed within 5 years of enrolment except for:
- Patients with any other severe concurrent disease, which may increase the risk associated with study participation or study drug administration and, in the judgement of the investigator, would make the patient inappropriate for entry into this study, including significant neurologic, psychiatric, infectious, hepatic, renal, or gastrointestinal diseases or laboratory abnormality.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NintedanibAlso: BIBF 1120, VargatefNintedanib (BIBF1120) 200mg twice daily PO, continuously, until progression or withdrawal from the treatment. | Drug | Nintedanib |
| PaclitaxelOvarian 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 | Chemotherapy |
| Pegylated Liposomal Doxorubicin (PLD)Also: CaelyxOvarian 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 | Chemotherapy |
| TopotecanAlso: HycamtinOvarian 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 | Chemotherapy |
| CarboplatinEndometrial 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 | Chemotherapy |
| DoxorubicinEndometrial 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. | Drug | Chemotherapy |
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
To estimate the progression free survival (PFS) in women with relapsed clear cell carcinoma of the ovary, peritoneum or fallopian tube treated with Nintedanib and compare this to PFS in women treated with chemotherapy.
8 secondary outcomes
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
Disease control rate
Time frame: 12 weeks
Quality of Life (QoL)
Time frame: up to 5 years
Quality of Life (QoL)
Time frame: up to 5 years
Quality of Life - recent symptoms of disease and treatment
Time frame: up to 5 years
Q-TWIST (Quality-Adjusted Time Without Symptoms of Disease or Toxicity of Treatment)
Time frame: up to 5 years
Response Rate
Time frame: up to 2 years
Toxicity
Time frame: median 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2016.
- Derived from this study: PubMed 37185961Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.
- Individual participant dataSharing planned: Yes. It is proposed that data generated by the study will be available 2 years after completion of the trial, or after publication of the first major paper describing the dataset, whichever occurs sooner.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claire A Lawless contact
Rosalind Glasspool principal investigator
NHS Greater Glasgow and Clyde
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nintedanib, Paclitaxel and Pegylated Liposomal Doxorubicin (PLD) in people with Ovarian Clear Cell Carcinoma and Endometrial Clear Cell Carcinoma, run by NHS Greater Glasgow and Clyde at 17 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Claire A Lawless (claire.lawless@glasgow.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02866370, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2016; AzTrials last refreshed its copy on 7 Nov 2026.