Clinical Trials /

Olaparib +/- Cediranib or Chemotherapy in Patients With Platinum-resistant Ovarian Cancer

NCT03117933

Description:

The trial will compare the drugs olaparib and cediranib with standard chemotherapy in platinum resistant ovarian cancer. Patients will be randomised to one of three treatment groups: olaparib only, olaparib and cediranib and the control group paclitaxel. The aim is to compare efficacy of the 3 treatments and also how well each treatment is tolerated including the participants quality of life.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Olaparib +/- Cediranib or Chemotherapy in Patients With Platinum-resistant Ovarian Cancer
  • Official Title: Randomised Phase II Trial of Olaparib, Chemotherapy or Olaparib and Cediranib in Patients With Platinum-resistant Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: OCTO_062
  • SECONDARY ID: 2016-000559-28
  • SECONDARY ID: 16/LO/2150
  • NCT ID: NCT03117933

Conditions

  • Ovarian Cancer

Interventions

DrugSynonymsArms
OlaparibB: Olaparib
CediranibC: Olaparib and Cediranib
PaclitaxelA: Paclitaxel

Purpose

The trial will compare the drugs olaparib and cediranib with standard chemotherapy in platinum resistant ovarian cancer. Patients will be randomised to one of three treatment groups: olaparib only, olaparib and cediranib and the control group paclitaxel. The aim is to compare efficacy of the 3 treatments and also how well each treatment is tolerated including the participants quality of life.

Detailed Description

      Olaparib is a PARP inhibitor which targets BRCA1/2 mutated tumour cells and cediranib is an
      anti-angiogenic drug which reduces blood supply to the tumour, suppressing tumour viability.
      Phase I/II trials of both drugs have shown these are well tolerated alone or in combination
      in ovarian cancer.

      The trial aims to compare the efficacy of the combination and of olaparib alone with
      paclitaxel chemotherapy and whether the olaparib/cediranib combination is better tolerated
      thus improving quality of life. Secondly standard paclitaxel chemotherapy must be
      administered weekly at hospital whereas the olaparib/cediranib combination can be
      administered at home potentially also improving patient quality of life.

      Participants' tumours will be resistant to platinum based therapies. Participants will be
      randomised into one of the 3 treatment arms after stratification for prior
      PARP/anti-angiogenic treatments/BRCA status. Participants will be on trial up to 18 months.
    

Trial Arms

NameTypeDescriptionInterventions
A: PaclitaxelActive ComparatorPaclitaxel, IV weekly, 80mg/m2; until progression
  • Paclitaxel
B: OlaparibExperimentalOlaparib, oral, 300mg twice daily; until progression
  • Olaparib
C: Olaparib and CediranibExperimentalOlaparib, oral, 300mg twice daily and Cediranib, tablet, 20mg once daily; until progression
  • Olaparib
  • Cediranib

Eligibility Criteria

        Inclusion Criteria:

          1. Female patients, age ≥ 16 years with relapsed epithelial ovarian, primary peritoneal
             or fallopian tube cancer who have relapsed within 12 months of previous platinum-based
             therapy. Their most recent chemotherapy does not have to have been platinum-based.

          2. Patients can have received prior PARP inhibitor, but there must be a > 6 month
             interval since treatment.

          3. Patients can have received prior antiangiogenic therapy, but there must be a > 6 month
             interval since treatment; except for bevacizumab where a 6 week interval is required.

          4. Measurable disease by RECIST Version 1.1 performed in past 4 weeks. At least one
             lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10
             mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm)
             with computed tomography (CT) or magnetic resonance imaging (MRI) and which is
             suitable for accurate repeated measurements.

          5. Sufficient archival tissue confirming histological diagnosis available.

          6. ECOG PS 0-2

          7. Able to swallow and retain oral medications.

          8. Life expectancy > 12 weeks in terms of disease related mortality

          9. Patient is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up.

         10. Written (signed and dated) informed consent prior to any study specific procedures and
             be capable of co-operating with protocol.

         11. Patients must have

             • Haemoglobin ≥ 9.0 g/dL and no blood transfusions in the 28 days prior to
             randomisation

         12. Patients must have normal organ and bone marrow function measured within 14 days prior
             to administration of study treatment as defined below:

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

                  o No features suggestive of MDS/AML on peripheral blood smear

               -  White blood cells (WBC) > 3x109/L

               -  Platelet count > 100 x 109/L

               -  Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)

               -  AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver
                  metastases are present in which case it must be ≤ 5x ULN

               -  Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) or calculated
                  creatinine clearance >50 ml/min calculated using Cockroft-Gault, Jelliffe or
                  Wright (see Appendix 4)

               -  Urine dipstick for proteinuria <2+. If urine dipstick is ≥ 2+ on two occasions
                  more than one week apart then a 24-hour urine must demonstrate ≤ 1 g of protein
                  in 24 hours or protein/creatinine ratio < 1.5.

        Exclusion Criteria:

          1. Received previous single agent weekly paclitaxel for relapsed disease.

          2. Pregnant or breast-feeding women or women of childbearing potential unless effective
             methods of contraception are used during the trial and for 6 months after stopping
             treatment. Negative urine or serum pregnancy test within 28 days of study treatment,
             confirmed prior to treatment on day 1. Pregnancy test will be performed monthly in
             women of child bearing potential.

             Postmenopausal is defined as:

               -  Amenorrheic for 1 year or more following cessation of exogenous hormonal
                  treatments

               -  LH and FSH levels in the post-menopausal range for women under 50,

               -  radiation-induced oophorectomy with last menses >1 year ago,

               -  chemotherapy-induced menopause with >1 year interval since last menses, or
                  surgical sterilisation (bilateral oophorectomy or hysterectomy).

          3. Treatment with any other investigational agent, systemic chemotherapy, or
             participation in another interventional clinical trial within 28 days prior to
             enrolment.

          4. Radiotherapy within 2 weeks from the last dose prior to study treatment

          5. Started a stable dose of bisphosphonates for bone metastases less than 4 weeks prior
             to treatment with study drug e.g. patient is eligible and can continue to take
             bisphosphonates if these were started at least 4 weeks prior to treatment with study
             drug.

          6. Concomitant use of known CYP3A4 inhibitors such as ketoconazole, itraconazole,
             ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.

          7. Concomitant use of potent inducers of CYP3A4 such as rifampicin, carbamazepine,
             phenobarbital, phenytoin and St. John Wort.

          8. Persistent toxicities (>=CTCAE grade 2), with the exception of alopecia, caused by
             previous cancer therapy.

          9. Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or
             family history of long QT syndrome.

         10. Blood transfusions within 1 month prior to study start

         11. Patients with myelodysplastic syndrome/acute myeloid leukaemia.

         12. Patients with symptomatic, untreated, uncontrolled brain or meningeal metastases or
             tumour.

             a. A scan to confirm the absence of brain metastases is not required. b. Patients with
             radiological evidence of stable brain metastases are eligible, providing that they are
             asymptomatic and: i. Do not require corticosteroids, or ii. Have previously been
             treated with corticosteroids, with clinical and radiological evidence of stabilisation
             at least 10 days after discontinuation of steroids iii. The patient can receive a
             stable dose of corticosteroids before and during the study as long as these were
             started at least 28 days prior to treatment.

         13. Major surgery within 14 days of starting study treatment

         14. Patients who have not recovered from any effects of any major surgery.

         15. Patients considered a poor medical risk due to a serious, uncontrolled medical
             disorder, non-malignant systemic disease or active, uncontrolled infection. Examples
             include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3
             months) myocardial infarction, unstable spinal cord compression (untreated and
             unstable for at least 28 days prior to study entry), superior vena cava syndrome,
             extensive bilateral lung disease on HRCT scan

         16. Any psychiatric disorder that prohibits obtaining informed consent.

         17. Left Ventricular Ejection Fraction (LVEF) < institutional lower limit of normal, when:

             i. Prior treatment with anthracyclines (excluding liposomal doxorubicin) ii. Prior
             treatment with trastuzumab iii. A NYHA classification of II controlled with treatment
             (see Appendix 2) iv. Prior central thoracic RT, including RT to the heart v History of
             myocardial infarction within the prior 12 months

         18. Poorly controlled hypertension (persistently elevated > 150/100mmHg, either systolic
             or diastolic or both, despite anti-hypertensive medication)

         19. History of inflammatory bowel disease

         20. History of cerebrovascular accident (including transient ischaemic attacks) within
             last 12 months.

         21. Gastro intestinal impairment that could affect ability to take, or absorption of, oral
             medicines including sub- acute or complete bowel obstruction

         22. Evidence of severe or uncontrolled cardiac disease

         23. Evidence of active bleeding or bleeding diathesis. Defined as significant haemorrhage
             (>30mL bleeding/episode in previous 3 months) or haemoptysis (>5mL fresh blood in
             previous 4 weeks)

         24. Known treatment-limiting hypersensitivity to cediranib, olaparib, paclitaxel or any of
             its excipients

         25. Other psychological, social or medical condition, physical examination finding or a
             laboratory abnormality that the Investigator considers would make the patient a poor
             trial candidate or could interfere with protocol compliance or the interpretation of
             trial results.

         26. Any other active malignancy, with the exception of adequately treated cone-biopsied in
             situ carcinoma of the cervix uteri and non-melanoma skin lesions, requiring
             treatment/or whose prognosis will prevent readout from trial endpoints.

         27. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or
             HIV.

        28 Immunocompromised patients e.g., patients who are taking immunosuppressive drugs.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:16 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:up to 18 months
Safety Issue:
Description:Progression free survival (PFS), measured as time from date of randomisation to RECIST-defined progression or death from any cause (whichever is first)

Secondary Outcome Measures

Measure:Adverse events
Time Frame:up to 18 months
Safety Issue:
Description:Adverse events using CTCAE v4.03
Measure:Overall Survival
Time Frame:12 & 18 months
Safety Issue:
Description:Overall Survival
Measure:Objective Response Rate
Time Frame:up to 18 months
Safety Issue:
Description:Objective Response Rate based on RECIST v1.1
Measure:Objective Response Rate
Time Frame:up to 18 months
Safety Issue:
Description:Objective Response Rate based GCIG CA125
Measure:Quality of Life Outcomes
Time Frame:up to 18 months
Safety Issue:
Description:Quality of Life Outcomes based on EORTC-QLQ C30
Measure:Quality of Life Outcomes
Time Frame:up to 18 months
Safety Issue:
Description:Quality of Life Outcomes based on EQ5D
Measure:Quality of Life Outcomes
Time Frame:up to 18 months
Safety Issue:
Description:Quality of Life Outcomes based on OV28.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Oxford

Trial Keywords

  • BRCA1/2 mutation
  • Platinum resistance

Last Updated