Is it safe to add Cediranib to weekly paclitaxel chemotherapy in women with ovarian cancer who are at risk of developing malignant bowel obstruction?

Phase 1

• Conditions: Platinum-Resistant Ovarian Cancer; MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004618-93-GB
• Lead Sponsor: niversity of Manchester

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-05-16
• Last Update Posted: 21 May 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

There are two sets of inclusion criteria: one for treatment with paclitaxel and cediranib, and one for when patients switch treatment to cediranib and olaparib.

INITIAL TREATMENT (paclitaxel and cediranib):

1)Histologically confirmed, progressive, platinum-resistant or refractory, high-grade ovarian, fallopian tube or primary peritoneal cancer for which weekly paclitaxel would be a potential treatment option.
2)Aged 16 years or over.
3)Patients who are at risk of bowel obstruction are eligible for the trial. Features that are compatible with this diagnosis include increasing abdominal pain and swelling, borborygmi, change in bowel habit, extensive serosal disease or dilated or tethered bowel on radiological investigation. It is anticipated that one or more of these should be present in eligible patients. Previous bowel obstruction is permitted providing patients can take oral medication and there is no concern about absorption of oral medication. Recto sigmoid involvement is permitted.
4)Adequate haematological function: Hb = 100 g/l, Neutrophils = 1.5 x 109/l, Platelets = 100 x 109/l; coagulation: INR <1.4 (unless therapeutically anti-coagulated) and/or APPT ratio <1.4
5)Adequate renal function defined as GFR =50ml/min and Creatinine clearance =50 mL/min using modified Wright or Cockcroft-Gault formula.
6)Adequate liver function: bilirubin = 1.5 xULN, transaminases = 3 xULN.
7)Any number of previous anti-cancer treatments permitted including weekly paclitaxel in the first-line setting.
8)Controlled hypertension permitted. Patients must have a blood pressure (BP) of = Systolic BP (SBP) :150/ Diastolic BP (DBP) 90 mmHg, with or without anti-hypertensive medication. BP measurements must be taken in the clinic setting by a medical professional within 2 weeks prior to starting study. A maximum of 3 anti-hypertensive medications are permitted and it is strongly recommended that patients who are on 3 anti-hypertensive medications be followed by a cardiologist or a primary care physician for management of BP while on study.
9)ECOG performance status 0-2 and life expectancy of over 12 weeks.
10)Adequately controlled thyroid function, with no symptoms of thyroid dysfunction.
11)Measurable disease by RECIST 1.1.
12)Previous bevacizumab is permitted but patients cannot have been treated with VEGF RTKi previously.
13)Written informed consent.
14)Able to swallow and retain oral medications and without gastrointestinal (GI) illnesses that would preclude absorption of cediranib or olaparib.

SECOND TREATMENT (cediranib and olaparib):

1)Radiological evidence of PD that is measurable per RECIST v1.1.
2)Adequate haematological function: Hb = 100 g/l, Neutrophils = 1.5 x 10?/l, Platelets = 100 x 109/l; coagulation: INR <1.4 (unless therapeutically anti-coagulated) and/or APPT ratio <1.4.
3)Adequate renal function defined as GFR =50ml/min and Creatinine clearance =50 mL/min using modified Wright or Cockcroft-Gault formula
4)Adequate liver function: bilirubin =1.5xULN, transaminases=3xULN.
5)Controlled hypertension permitted. Patients must have a blood pressure (BP) of = SBP:150/ DBP 90 mmHg, with or without anti-hypertensive medication. BP measurements must be taken in the clinic setting by a medical professional within 2 weeks prior to starting study. A maximum of 3 anti-hypertensive medications are permitted and it is strongly recommended that patients who are on 3 anti-hypertensive medications be followed by a cardiologist o

Exclusion Criteria

There are two sets of exclusion criteria: one for treatment with paclitaxel and cediranib, and one for when patients switch treatment to cediranib and olaparib. The criteria have been edited from the Protocol to stay within the character limit.

INITIAL TREATMENT (paclitaxel and cediranib):
1)Patients with known hypersensitivity to olaparib, cediranib or paclitaxel or any of the excipients of the products.
2)Concurrent medical illness that would impact on compliance with the protocol including myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML) or with features suggestive of MDS/AML.
3)Uncontrolled brain metastases or seizures. A scan to confirm the absence of brain metastases is not required.
4)Known positivity for Hep B, Hep C or HIV.
5)Resting ECG with QTc > 470msec or family history of long QT syndrome.
6)Concomitant use of known strong CYP3A4/5 inhibitors such as such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir. Concomitant use of inducers or inhibitors (e.g., phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) is also excluded. The required washout period prior to starting olaparib is 2 weeks.
7)Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
8)Another cancer, active within the previous 5 years, except for adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin and no evidence of recurrence of other malignancy.
9)Pregnant or lactating. Pregnancy status in women of child bearing potential will be confirmed via a serum or urine pregnancy test prior to randomisation, monthly during the treatment period, and at the end of treatment assessment. In addition, women of child bearing potential MUST be willing to ensure they use effective contraception for four weeks before entering the trial, throughout the treatment period and for six months following the end of treatment. Acceptable methods of contraception are listed in Protocol.
10)Patients who are planning to receive maintenance bevacizumab.
11)Radiotherapy, surgery or tumour embolization within 28 days before cediranib.
12)Additional concurrent anti-cancer therapy.
13)Malabsorption e.g. uncontrolled diarrhoea or poorly controlled stoma.
14)Patients who have or have had prior leukoencephalopathy, recent arterial thromboembolic event (MI/CVA within previous 6 months), previous or concurrent fistula, previous or concurrent GI perforation, concurrent intra-abdominal abscess, previous VEGF RTKi or clinically relevant proteinuria.
15)Inability to comply with the protocol.
16)Major surgery within two weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
17)Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
18)Patients unable to swallow oral medication or with gastrointestinal disorders likely to interfere with absorption of study medication.
19)Patients receiving any systemic chemotherapy or radiotherapy (except for pa

Study & Design

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