Randomised Phase II Trial of Cediranib and Olaparib Maintenance in Advanced/Recurrent Cervical Cancer

Phase 1

• Conditions: Advanced recurrent and metastatic cervical cancer.; MedDRA version: 20.0 Level: LLT Classification code 10008231 Term: Cervical cancer recurrent System Organ Class: 100000004864; MedDRA version: 20.0 Level: LLT Classification code 10008235 Term: Cervical cancer stage III System Organ Class: 100000004864; MedDRA version: 20.0 Level: LLT Classification code 10008236 Term: Cervical cancer stage IV System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004215-13-GB
• Lead Sponsor: The Clatterbridge Cancer Centre NHS Foundation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-10-27
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 108

Inclusion Criteria

1.Patients over 18 years of age
2.Histologically proven carcinoma of the cervix (squamous, adenocarcinoma or mixed adeno/squamous).
3.Completion of first line platinum-based chemotherapy for advanced /recurrent disease, leading to either a complete response, partial response or stable disease.
4.ECOG performance status 0 or 1
5.Randomisation within 6 weeks of completion of chemotherapy
6.Patients may have received previous chemoradiotherapy and neoadjuvant chemotherapy given with a curative intent.
7.Creatinine Clearance = 51mls/min
8.Adequate haematological and biochemical function, as follows:
Haemoglobin > 10g/dl (with no blood transfusion in the 28 days prior to randomisation) Neutrophils > 1.5 x 109/l
Platelets > 100 x 109/l
Bilirubin < 1.5 x ULN
ALT or AST/ SGOT < 3 x ULN (or =5 x ULN if hepatic metastases present)
Alkaline Phosphatase < 3 x ULN (or =5 x ULN if hepatic metastases present)
Adequate coagulation, as follows:
Prothrombin ratio (PTR) / INR = 1.5 or
PTR / INR between 2.0 and 3.0 for patients on stable doses of anticoagulants
Partial thromboplastin time <1.2 x control
9.Life expectancy >12 weeks.
10.Informed written consent
11.Contrast enhanced computerised tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen and pelvis and a CT scan of the chest within 28 days prior to commencing randomisation (with RECIST 1.1)
12.Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
13.Able to swallow and retain oral medications and without gastrointestinal (GI) illnesses that would preclude absorption of cediranib or olaparib.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 54
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 54

Exclusion Criteria

1.Disease that is potentially treatable with exenterative surgery.
2.Relapse confined to the pelvis after radical surgery in circumstance where radiotherapy or chemoradiotherapy would be appropriate.
3.More than one line of prior chemotherapy for advanced/recurrent disease. Neoadjuvant chemotherapy is not counted.
4.Prior treatment with anti-angiogenic agents (with the exception of bevacizumab given as part of first line chemotherapy)
5.Persisting =Grade 2 CTCAE from previous anti-cancer previous systemic anti-cancer therapy except haematological toxicity (see inclusion criteria Adequate haematological function”) and alopecia.
6.History of other malignancy within the previous 5 years except for:
Curatively treated basal cell or squamous cell carcinoma of skin; in situ cancer of the cervix, ductal carcinoma in situ of the breast or stage 1, grade 1 endometrial carcinoma.
Curatively treated other solid tumors including lymphomas (without bone marrow involvement) with no evidence of disease for =5 years prior to start of IPs.
7.Pregnant or lactating women.
8.Fertile woman of childbearing potential not willing to use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) for the study duration and at least six months afterwards
9.Evidence of uncontrolled infection. (Defined as infection that cannot be resolved readily with antibiotics prior to patient entry into the trial for example a pelvic collection)
10.History of pelvic fistulae.
11.History of abdominal fistula that has been surgically corrected within 6 months of starting treatment. Patient should be deemed low risk of recurrent fistula
12.Sub-acute or acute intestinal obstruction.
13.Major surgery within 28 days or anticipated while on study.
14.Non-healing wound, ulcer or bone fracture.
15.Active bleeding.
16.History or evidence of thrombotic or haemorrhagic disorders.
17.History of stroke or transient ischemic attack within 6 months
18.Proteinuria > 1+ on dipstick on two consecutive dipsticks taken no less than 1 week apart, unless urinary protein is <1.5g in a 24 hour period.
19.Significant cardiovascular disease (arterial thrombotic event within 12 months, uncontrolled hypertension, myocardial infarction or angina within 6 months, NYHA grade 2 or worse congestive cardiac failure, grade = 3 peripheral vascular disease or cardiac arrhythmia requiring medication). Patients with rate-controlled atrial fibrillation are eligible.
20.Prolonged QTc (corrected) interval of >470ms on ECG or a family history of long QT syndrome.
21.Patients with symptomatic uncontrolled brain or meningeal metastases CNS disease
(A scan to confirm the absence of brain metastases is not required)
22.A history of poorly controlled hypertension or resting BP>140/90 mmHG in the presence or absence of a stable regimen of anti-hypertensive therapy (measurements will be made after the patient has been resting supine for a minimum of 5 minutes. Two or more readings should be taken at 2 minute int

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified