Does Cediranib Prevent Bowel Perforation in Platinum-resistant Ovarian Cancer

NCT07648745 | Completed Phase 2 DMC

• 3 other identifiers: R1205022016-004618-93ESR-15-11304
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Ovarian cancer can often grow and cause obstructions in the bowel. These obstructions usually cannot be removed with surgery and can be fatal. This trial is testing whether a drug called cediranib can be used safely together with paclitaxel chemotherapy to treat ovarian cancer in women at risk of bowel obstructions. All participants will receive the cediranib/paclitaxel combination, and if the cancer worsens the participant will stop receiving paclitaxel and may receive an additional drug, olaparib, together with cediranib.

Conditions

Bowel Obstruction; Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer

Outcome Measures

Primary Outcomes (1)

• The number of patients free of grade III-V gastrointestinal perforation or fistula causally related to cediranib.

  The number of patients free of grade III-V gastrointestinal perforation or fistula during cediranib treatment. This is causally related to cediranib or the cediranib olaparib combination, during cediranib treatment until patient withdraws, dies or has been treated with cediranib for at least 18 weeks, and for 28 days following the last dose. The proportion will be calculated with an exact 95% confidence interval (CI) calculated using the Clopper-Pearson method.

  From date of registration until 28 days after the last dose of cediranib, or until death, whichever occurs first. Minimum assessment period: 18 weeks of cediranib treatment or until prior withdrawal/death.

Secondary Outcomes (10)

• Proportion of participants hospitalised for bowel obstruction

  From date of registration until patient withdraws from/stops cediranib treatment, dies or has been treated with cediranib for at least 18 weeks. All patients will be followed up for 28 days after the last dose of study drug.

• The number of grade III or more toxicities excluding gastrointestinal perforation/ fistula as assessed by CTCAE 4.03.

  From date of registration until patient withdraws from/stops cediranib treatment, dies or has been treated with cediranib for at least 18 weeks. All patients will be followed up for 28 days after the last dose of study drug.

• Total dose of paclitaxel delivered in Component 1

  From first dose of paclitaxel to last dose of paclitaxel, up to 18 weeks

• Relative dose intensity of paclitaxel in Component 1

  From first dose of paclitaxel to last dose of paclitaxel, up to 18 weeks

• Total dose of cediranib delivered in Component 1

  From first dose of cediranib to last dose of cediranib or data cutoff, up to 18 weeks

Other Outcomes (4)

• Association of prior bevacizumab exposure with treatment-related toxicities, objective response rate, progression free survival, and overall survival

  From date of registration until death, withdrawal, or database lock, assessed up to 36 months

• The number of grade III or more toxicities when on olaparib/cediranib treatment

  For the duration of treatment, up to 36 months. Treatment on component 2 will continue until second PD unless one of the following occurs: • patient withdrawal. • unacceptable toxicity. • intolerance to treatment.

• Association of BRCA1/2 mutation status with treatment related toxicities, objective response rate, progression free survival, and overall survival in patients receiving olaparib plus cediranib

  From date of registration until death, withdrawal, or database lock, assessed up to 36 months

Study Arms (1)

Cediranib

EXPERIMENTAL

Cediranib 20mg/day with weekly paclitaxel 70mg/m2/week. At the point of developing progressive disease (PD), patients will have the option of ceasing paclitaxel and continuing cediranib 20mg/day with olaparib 300mg bd continuously until further PD occurs.

Drug: Cediranib

Interventions

Cediranib DRUG

Cediranib in combination with weekly paclitaxel

Also known as: AZD-2171, cediranib maleate

Cediranib

Eligibility Criteria

• Age: 16 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Aged 16 years or over
• At risk of bowel obstruction: features compatible with this include increasing abdominal pain and swelling, borborygmi, change in bowel habit, extensive serosal disease or dilated or tethered bowel on radiological investigation. 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
• 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
• Adequate renal function defined as GFR ≥50ml/min and Creatinine clearance ≥50 mL/min using modified Wright or Cockcroft-Gault formula
• Adequate liver function: bilirubin ≤ 1.5 x ULN, transaminases ≤ 3 x ULN
• Any number of previous anti-cancer treatments permitted including weekly paclitaxel in the first-line setting
• 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
• ECOG performance status 0-2 and life expectancy of over 12 weeks.
• Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
• Measurable disease by RECIST v1.1
• Previous bevacizumab is permitted but patients cannot have been treated with VEGF RTKi previously
• Written informed consent
• Able to swallow and retain oral medications and without gastrointestinal (GI) illnesses that would preclude absorption of cediranib or olaparib.
• Radiological evidence of PD that is measurable per RECIST v1.1

You may not qualify if:

• Patients with a known hypersensitivity to olaparib, cediranib or paclitaxel or any of the excipients of the products
• 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
• Uncontrolled brain metastases or seizures. A scan to confirm the absence of brain metastases is not required. Central nervous system metastases:
• Symptomatic uncontrolled brain metastases requiring corticosteroid treatment
• History of spinal cord compression unless after definitive treatment the patient has clinically stable disease (SD) for at least 28 days prior to starting IMPs. In the absence of these features and in an asymptomatic patient a scan to confirm the absence of brain metastases is not required
• Known positivity for Hep B, Hep C or HIV
• Resting ECG with QTc \> 470msec on 2 or more time points within a 24-hour period or family history of long QT syndrome
• 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
• 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.
• Another cancer, which has been 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.
• 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:
• i. true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant) ii. a combination of male condom plus one of:
• vasectomised sexual partner, with participant assurance that partner received post-vasectomy confirmation of azoospermia
• Tubal occlusion
• Intrauterine device provided coils are copper-banded

Sponsors & Collaborators

• Prof Gordon Jayson: lead
• AstraZeneca: collaborator
• Cardiff University: collaborator

Study Sites (1)

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Intestinal Obstruction; Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

cediranib

Condition Hierarchy (Ancestors)

Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Study Officials

• Andrew Clamp

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medical Oncology

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: June 15, 2026
• Study Start: May 14, 2018
• Primary Completion: January 14, 2025
• Study Completion: January 14, 2025
• Last Updated: June 15, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)