A Multicentre Phase II Trial of Durvalumab Versus Physician's Choice Chemotherapy in Recurrent Ovarian Clear Cell Adenocarcinomas

NCT03405454 | Unknown Phase 2

• 1 other identifier: GY02/09/16
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to find out if treatment with a study drug, durvalumab has beneficial effects in people who have recurrent ovarian clear cell cancer and to determine what effects (both good and bad) it has on them and their cancer.

Conditions

Ovarian Clear Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression free survival (PFS) is defined as the time from the first day of treatment to the first observation of radiological or clinical disease progression or death due to any cause or last follow-up. The progression will be defined by RECIST criteria v1.1 for patients on the chemotherapy arm which includes first instance of more than 20% increase in the sum of diameters or unequivocal progression in non-target disease. The sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) is calculated at baseline and at each tumor assessment.

  4 years

Secondary Outcomes (4)

• Objective Response Rate

  4 years

• Overall survival

  4 years

• Health related Quality of life (HRQOL)

  4 years

• Adverse event profile

  4 years

Study Arms (2)

standard chemotherapy

ACTIVE COMPARATOR

Patients on physician's choice of chemotherapy are allowed to receive any systemic chemotherapy either as a single agent or in combination. However, biologics( including bevacizumab) and oral tyrosine kinase inhibitors will not be allowed for patients on this arm

Drug: standard chemotherapy

durvalumab

EXPERIMENTAL

Patients on durvalumab will be given at 1500mg fixed dose every 4 weeks for 24 months

Drug: durvalumab

Interventions

durvalumab DRUG

Durvalumab will be given at 1500mg fixed dose every 4 weeks for 24 months or until the appearance of significant treatment-related toxicity or disease progression

durvalumab

standard chemotherapy DRUG

chemotherapy treatment will be administered as per local institutional guidelines

standard chemotherapy

Eligibility Criteria

• Age: 21 Years - 99 Years
• Gender Eligibility Details: Only the females are affected by the ovarian clear cell carcinoma (OCCC).
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed, written and dated informed consent prior to any study specific procedure
• Female aged 18 years (21 years in Singapore) or older
• Have histologically documented diagnosis of ovarian clear cell carcinoma as evidenced by WT1 negativity. For tumors with a mixed histology, at least 70% of the tumor must consist of clear cell carcinoma.
• Provision of an archived tumour tissue block (or at least 10 newly cut unstained slides) where such samples exist in a quantity sufficient to allow for analysis
• Patients must have had a prior line of platinum-based chemotherap y in the course of their treatment paradigm
• A maximum of 4 prior lines of systemic treatment regimens will be allowed and may include chemotherapy and biologics (prior immune checkpoint inhibitor treatment will not be permitted).
• Meet RECIST criteria (version 1.1) within 28 days of start of treatment by having measurable disease defined as one or more lesions that can be accurately measured at baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have a short axis of ≥ 15mm with CT or MRI and which is suitable for repeated measurements). Patients must have radiographic evidence of disease progression following most recent line of treatment. Areas of previous radiation may not serve as measurable disease unless there is evidence of progression post radiation.
• At time of registration, if the patient has had previous treatment it must have been at least 4 weeks since major surgery or radiation therapy; four weeks from any other previous anti-cancer therapy including biologics. Patients must have recovered from their treatment-related events to ≤1 with the exception of alopecia and neuropathy (≤ 2 sufficient).
• Have clinically acceptable laboratory screening results within certain limits specified below:
• AST and ALT ≤ 2.5 times upper limit of normal (ULN), with the exception of:
• i. Patients with documented liver metastasis: AST and/or ALT ≤ 5 X ULN
• Total bilirubin ≤ ULN; patients with known Gilbert disease who have serum bilirubin level ≤ 3 X ULN may be enrolled
• Creatinine ≤ 1.5 x UL
• Absolute neutrophil count ≥ 1500 cells/mm
• Platelets ≥ 100,000/mm3

You may not qualify if:

• Women who are pregnant or nursing
• Prior exposure to an immune checkpoint inhibitor (anti-PD-1 or anti-PDL-1 antibody)
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1
• Active or prior documented autoimmune disease within the past 2 years. NOTE: Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
• Have active, acute, or chronic clinically significant infections or bleeding including but not limited to active bleeding diatheses, patients known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV),
• History of primary immunodeficiency
• History of allogeneic organ transplant
• Known history of previous clinical diagnosis of tuberculosis
• Have uncontrolled hypertension (systolic blood pressure greater than 150mmHg or diastolic blood pressure greater than 100mmHg);
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months or unstable angina
• Chronic atrial fibrillation or QTc interval corrected for heart rate of greater than 470 msec. calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction.
• By Fridericia's formula: QTc = QT/(RR\^0.33) Where - RR interval = 60 / HR ; HR = Heart rate in beats per minute.
• Have additional uncontrolled serious medical or psychiatric illness.
• Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of investigational product

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (2)

National University Hospital

Singapore, 164119, Singapore

RECRUITING

National Cancer Centre

Singapore, Singapore

RECRUITING

Related Publications (4)

• Mackay HJ, Brady MF, Oza AM, Reuss A, Pujade-Lauraine E, Swart AM, Siddiqui N, Colombo N, Bookman MA, Pfisterer J, du Bois A; Gynecologic Cancer InterGroup. Prognostic relevance of uncommon ovarian histology in women with stage III/IV epithelial ovarian cancer. Int J Gynecol Cancer. 2010 Aug;20(6):945-52. doi: 10.1111/IGC.0b013e3181dd0110.

  PMID: 20683400 BACKGROUND

• Kobel M, Kalloger SE, Huntsman DG, Santos JL, Swenerton KD, Seidman JD, Gilks CB; Cheryl Brown Ovarian Cancer Outcomes Unit of the British Columbia Cancer Agency, Vancouver BC. Differences in tumor type in low-stage versus high-stage ovarian carcinomas. Int J Gynecol Pathol. 2010 May;29(3):203-11. doi: 10.1097/PGP.0b013e3181c042b6.

  PMID: 20407318 BACKGROUND

• Yamagami W, Aoki D. Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology. J Obstet Gynaecol Res. 2015 Feb;41(2):167-77. doi: 10.1111/jog.12596. Epub 2014 Nov 5.

  PMID: 25370711 BACKGROUND

• Ngoi NY, Heong V, Ow S, Chay WY, Kim HS, Choi CH, Goss G, Goh JC, Tai BC, Lim DG, Kaliaperumal N, Au VB, Connolly JE, Kim JW, Friedlander M, Kim K, Tan DS. A multicenter phase II randomized trial of durvalumab (MEDI-4736) versus physician's choice chemotherapy in recurrent ovarian clear cell adenocarcinoma (MOCCA). Int J Gynecol Cancer. 2020 Aug;30(8):1239-1242. doi: 10.1136/ijgc-2020-001604. Epub 2020 Jun 25.

  PMID: 32591370 DERIVED

MeSH Terms

Interventions

durvalumab

Study Officials

• David SP Tan

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David SP Tan

CONTACT

(65) 6779 5555; david_sp_tan@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized 2:1 to receive either durvalumab at a dose of 1500mg every four weeks for a maximum of 24 months or physician's choice of chemotherapy

Study Record Dates

• First Submitted: October 19, 2017
• First Posted: January 23, 2018
• Study Start: October 9, 2017
• Primary Completion: September 15, 2021
• Study Completion: March 15, 2022
• Last Updated: May 18, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

SG (2)