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Platinum-resistant Recurrent Ovarian CancerPhase 2NCT03699449

An uMbrella Study of BIomarker-driven Targeted Therapy In Patients With Platinum-resistant Recurrent OvariaN Cancer(AMBITION)

A Phase 2 study testing olaparib+cediranib combination therapy, durvalumab + olaparib combination therapy and durvalumab + chemotherapy treatment in people with Platinum-resistant Recurrent Ovarian Cancer, run by Yonsei University at 3 sites in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study is a pilot study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer. More specifically, this is a randomized, multi-center, open label, phase II study for Homologous Recombination Deficiency(HRD)+ patients and a biomarker-driven multiple-arm phase II study for… Read more about this study

Who is it for?
Ages 20 years and older, women only
What is being tested?
olaparib+cediranib combination therapy, durvalumab + olaparib combination therapy and durvalumab + chemotherapy treatment
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
104 participants
Where
3 sitesSouth Korea
Study dates
26 Nov 2018to Sep 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed high-grade serous or high-grade endometrioid ovarian, primary peritoneal, or fallopian tube cancers.
  • Disease progression within 6 months of completing platinum-based chemotherapy
  • Who had received ≥ two lines of chemotherapy
  • Provision of informed consent prior to any study specific procedures
  • Female aged 20 years older at time of study entry
  • Body weight >30kg
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  • Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below: 1) Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days, 2) Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, 3) Platelet count ≥ 100 x 109/L, 4) Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), 5) Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 3 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN, 6) Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of ≥50 mL/min: Estimated creatinine clearance = (140-age [years]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72, 7) a where F=0.85 for females and F=1 for males, 8) Urine protein: creatinine ratio (UPC) ≤1 OR ≤2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart. Patients with 2+ proteinuria on dipstick must also have UPC <0.5 on 2 consecutive samples. 9) Adequately controlled blood pressure (systolic blood pressure (SBP) ≤140 mmHg; diastolic blood pressure (DBP) ≤ 90mmHg) on maximum of 3 antihypertensive medications. Patients must have a blood pressure (BP) of ≤ 140/90 mmHg taken in the clinic setting by a medical professional within 2 weeks prior to starting study. It is strongly recommended that patients who are on three antihypertensive medications be followed by a cardiologist or a primary care physician for management of BP while on study. 10) Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patients must have a life expectancy ≥ 16 weeks.
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined as: 1) Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments, 2) Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50, 3) radiation-induced oophorectomy with last menses >1 year ago, 4) chemotherapy-induced menopause with >1 year interval since last menses, 5) surgical sterilisation (bilateral oophorectomy or hysterectomy)
  • Patients is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
  • Patients must have evaluable disease - define as one of the following: 12.1 RECIST 1.1 measurable disease OR, 12.2 Evaluable disease (defined as solid and cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or pleural effusion that has been pathologically demonstrated to be disease-related) in the setting of a CA125 > 2 times ULN.
  • Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer must be available for central testing. If there is not written confirmation of the availability of an archived tumour sample prior to enrolment the patient is not eligible for the study. For inclusion in i) the optional exploratory genetic research and ii) the optional biomarker research, patients must fulfil the following criteria: 1) Provision of informed consent for genetic research, 2) Provision of informed consent for biomarker research
  • If a patient declines to participate in the optional exploratory genetic research or the optional biomarker research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study.

Who cannot join

  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
  • Previous enrollment or randomization in the present study
  • Participation in another clinical study with an investigational product during the last 60 months
  • Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
  • Any previous treatment with poly ADP ribose polymerase(PARP) inhibitor (including olaparib), anti-PD-1, PD-L1, CTLA-4 (including durvalumab and tremelimumab).
  • Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years. Patients with a history of localised triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
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  • Resting ECG with Corrected QT Interval(QTc) > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
  • Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
  • Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) ≤21 days prior to the first dose of study drug If sufficient wash-out time has not occurred due to the schedule or Pharmacokinetics(PK) properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca/MedImmune and the investigator
  • Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
  • Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
  • Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
  • Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria : 1) Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Principal Investigator. 2) Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Principal Investigator.
  • Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of Myelodysplastic syndrome/Acute myeloid leukemia(MDS/AML).
  • Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.

Trial locations and contacts

3 sites in 1 country.

Jung-Yun Lee, MD, Ph.D contact

82-2-2228-2246

JUNGYUNLEE@yuhs.ac

South Korea3 sites, 3 recruiting

  • Seoul National University Hospital

    Seoul, 03080

    Jae-Woen Kim, MD, Ph.D, +82-2-2072-3511, kjwksh@snu.ac.kr

    Jae-Woen Kim, MD, Ph.D

    Recruiting

  • Yonsei University Health System, Severance Hospital

    Seoul, 03722

    Jung-Yun Lee, 82-2-2228-2230, jungyunlee@yuhs.ac

    Recruiting

  • Samsung Medical Center

    Seoul, 06351

    Byoung-Gie Kim, MD, Ph.D, 82-2-3410-3513, bgkim@skku.edu

    Byoung-Gie Kim, MD, Ph.D

    Recruiting

Other trials in South Korea

About this study

This study is a pilot study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer. More specifically, this is a randomized, multi-center, open label, phase II study for Homologous Recombination Deficiency(HRD)+ patients and a biomarker-driven multiple-arm phase II study for Homologous Recombination Deficiency(HRD)- patients.

This study will consist of a number of study modules (substudies), each evaluating the antitumor activity of targeted agents in patients whose tumors express specific phenotype relevant to the molecules under investigation.

Being tested
olaparib+cediranib combination therapy, durvalumab + olaparib combination therapy, durvalumab + chemotherapy treatment, durvalumab + tremelimumab + chemotherapy treatment, durvalumab + tremelimumab + paclitaxel treatment

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • olaparib+cediranib combination therapyDrug

    Cediranib (30mg p.o. qd) + Olaparib (200mg p.o. bid) until disease progression

  • durvalumab + olaparib combination therapyDrug

    Durvalumab (1500mg i.v. every 4 weeks starting on week 5 day1 for up to 12 months) + Olaparib (300mg p.o. bid) until disease progression

  • durvalumab + chemotherapy treatmentDrug

    Durvalumab (1500mg i.v. every 4 weeks for up to 24 months) + non-platinum-based standard of care chemotherapy (weekly paclitaxel, topotecan, or Pegylated liposomal doxorubicin(PLD) up to 6 cycles)

    Chemotherapy regimen:

    Weekly Paclitaxel 80mg/m2 (day 1,8,15,22 every 4 weeks), PLD (40mg/m2 on D1 every 4 weeks), topotecan (4mg/m2 on D1,8,15 every 4 weeks)

  • durvalumab + tremelimumab + chemotherapy treatmentDrug

    Durvalumab (1500mg i.v. every 4 weeks for up to 24 months) + Tremelimumab (75mg i.v. every 4 weeks for up to 4 doses) + non-platinum-based standard of care chemotherapy (weekly paclitaxel, topotecan, or Pegylated liposomal doxorubicin (PLD) up to 4 cycles)

    Chemotherapy regimen:

    Weekly Paclitaxel 80mg/m2 (day 1,8,15,22 every 4 weeks), PLD (40mg/m2 on D1 every 4 weeks), topotecan (4mg/m2 on D1,8,15 every 4 weeks)

  • durvalumab + tremelimumab + paclitaxel treatmentDrug

    Durvalumab (1500mg i.v. every 4 weeks for up to 24 months) + Tremelimumab (300mg i.v. once) + non-platinum-based standard of care chemotherapy (weekly paclitaxel up to 4 cycles)

    Chemotherapy regimen:

    Weekly Paclitaxel 60mg/m2 (day 1,8,15 every 4 weeks)

  • durvalumab +chemotherapy treatmentDrug

    Durvalumab (1500mg i.v. every 4 weeks for up to 24 months) + non-platinum-based standard of care chemotherapy (paclitaxel, topotecan, or Pegylated liposomal doxorubicin(PLD) up to 4 cycles)

    Chemotherapy regimen:

    Weekly Paclitaxel 80mg/m2 (day 1,8,15,22 every 4 weeks), PLD (40mg/m2 on D1 every 4 weeks), topotecan (4mg/m2 on D1,8,15 every 4 weeks)

Study groups in NCT03699449
Study groupRoleWhat they receive
olaparib + cediranibExperimentalolaparib+cediranib combination therapy
Receives: Drug: olaparib+cediranib combination therapy
durvalumab + olaparibExperimentaldurvalumab + olaparib combination therapy
Receives: Drug: durvalumab + olaparib combination therapy
durvalumab + chemotherapyExperimentaldurvalumab +chemotherapy
Receives: Drug: durvalumab + chemotherapy treatment
durvalumab + tremelimumab + chemotherapyExperimentaldurvalumab + tremelimumab + chemotherapy
Receives: Drug: durvalumab + tremelimumab + chemotherapy treatment
durvalumab + tremelimumab + paclitaxelExperimentaldurvalumab + tremelimumab + paclitaxel
Receives: Drug: durvalumab + tremelimumab + paclitaxel treatment
durvalumab +chemotherapyExperimentaldurvalumab +chemotherapy
Receives: Drug: durvalumab +chemotherapy treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. objective response rate by RECIST 1.1

    The primary endpoint of the study is objective response rate by RECIST 1.1 (Time frame: up to 6 months after treatment initiation)

    Measured: 6 months after treatment initiation

Secondary outcomes (4)

  1. Progression-free survival(PFS)

    Measured: up to 3 years

  2. overall-survival(OS)

    Measured: up to 3 years

  3. immune-related Response Criteria

    Measured: up to 3 years

  4. Duration of response

    Measured: up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2018
  2. Study start26 Nov 2018
  3. Primary completionSep 2022 (estimated)
  4. Study completionSep 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a randomized, multi-center, open label, phase II study for HRD+ patients and a biomarker-driven multiple-arm phase II study for HRD- patients. This study will consist of a number of study modules (substudies), each evaluating the antitumor activity of targeted agents in patients whose tumors express specific phenotype relevant to the molecules under investigation.
Masking
None (open label)
Enrolment
104 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03699449
Sponsor's protocol ID
4-2018-0749
Other IDs
KCT0003283, KGOG3045, 2018-10-009, 1810-035-977, ESR-17-12678
Status last verified
Mar 2021
First submitted
2 Oct 2018
Last updated
1 Apr 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: Study protocol and even raw data will be released after further discussion among researchers.

Publications

  • 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.

    PubMed 37185961

  • Lee JY, Kim BG, Kim JW, Lee JB, Park E, Joung JG, Kim S, Choi CH, Kim HS; Korean Gynecologic Oncology Group (KGOG) investigators. Biomarker-guided targeted therapy in platinum-resistant ovarian cancer (AMBITION; KGOG 3045): a multicentre, open-label, five-arm, uncontrolled, umbrella trial. J Gynecol Oncol. 2022 Jul;33(4):e45. doi: 10.3802/jgo.2022.33.e45. Epub 2022 Mar 4.

    PubMed 35320892

  • Lee JY, Yi JY, Kim HS, Lim J, Kim S, Nam BH, Kim HS, Kim JW, Choi CH, Kim BG; KGOG investigators. An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer: a Korean Gynecologic Oncology Group study (KGOG 3045), AMBITION. Jpn J Clin Oncol. 2019 Aug 1;49(8):789-792. doi: 10.1093/jjco/hyz085.

    PubMed 31671191

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing olaparib+cediranib combination therapy, durvalumab + olaparib combination therapy and durvalumab + chemotherapy treatment in people with Platinum-resistant Recurrent Ovarian Cancer, run by Yonsei University at 3 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Jung-Yun Lee, MD, Ph.D (82-2-2228-2246, JUNGYUNLEE@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

objective response rate by RECIST 1.1 (time frame: 6 months after treatment initiation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03699449, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2021.

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