Study Of Nintedanib Compared To Chemotherapy in Patients With Recurrent Clear Cell Carcinoma Of The Ovary Or Endometrium
NiCCC
A Randomised Phase II Study Of Nintedanib (BIBF1120) Compared To Chemotherapy in Patients With Recurrent Clear Cell Carcinoma Of The Ovary Or Endometrium
5 other identifiers
interventional
120
1 country
17
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Apr 2015
Longer than P75 for phase_2
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2015
CompletedFirst Submitted
Initial submission to the registry
July 22, 2016
CompletedFirst Posted
Study publicly available on registry
August 15, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2021
CompletedAugust 15, 2016
July 1, 2016
4.9 years
July 22, 2016
August 10, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
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.
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
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
12 weeks
Quality of Life (QoL)
up to 5 years
Quality of Life (QoL)
up to 5 years
Quality of Life - recent symptoms of disease and treatment
up to 5 years
- +3 more secondary outcomes
Study Arms (2)
Nintedanib
EXPERIMENTALNintedanib (BIBF1120) 200mg twice daily PO, continuously
Chemotherapy
ACTIVE COMPARATOROvarian 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.
Interventions
Nintedanib (BIBF1120) 200mg twice daily PO, continuously, until progression or withdrawal from the treatment.
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.
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.
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.
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.
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.
Eligibility Criteria
You may qualify if:
- 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
- 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.
You may not qualify if:
- 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)
- 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.
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NHS Greater Glasgow and Clydelead
- Boehringer Ingelheimcollaborator
- Cancer Research UKcollaborator
- European Organisation for Research and Treatment of Cancer - EORTCcollaborator
- Nordic Society of Gynaecological Oncology - Clinical Trials Unitcollaborator
- ARCAGY/ GINECO GROUPcollaborator
Study Sites (17)
Beatson West of Scotland Cancer Centre
Glasgow, Lanarkshire, G12 0YN, United Kingdom
Ninewells Hospital
Dundee, Tayside, United Kingdom
Clatterbridge Cancer Centre
Liverpool, Wirral, United Kingdom
Belfast City Hospital (Northern Ireland Cancer Centre)
Belfast, United Kingdom
Bristol Heamatology and Cancer Centre
Bristol, United Kingdom
Velindre Hospital
Cardiff, United Kingdom
Kent & Canterbury Hospital
Kent, United Kingdom
Queen Elizabeth Queen Mother Hospital
Kent, United Kingdom
William Harvey Hospital
Kent, United Kingdom
St James Hospital
Leeds, United Kingdom
Guy's Hosital
London, United Kingdom
Royal Marsden Hospital
London, United Kingdom
St Bartholomew's Hospital
London, United Kingdom
University College London Hospital
London, United Kingdom
The Christie Hospital
Manchester, United Kingdom
Great Western Hospital
Swindon, United Kingdom
Musgrove Park Hospital
Taunton, United Kingdom
Related Publications (1)
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.
PMID: 37185961DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rosalind Glasspool
NHS Greater Glasgow and Clyde
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 22, 2016
First Posted
August 15, 2016
Study Start
April 1, 2015
Primary Completion
March 1, 2020
Study Completion
March 1, 2021
Last Updated
August 15, 2016
Record last verified: 2016-07
Data Sharing
- IPD Sharing
- Will share
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.