UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A Phase I/II, open-label, non-randomized, multi-center, dose escalation study of olaparib in combination with eribulin mesylate to assess the safety, tolerability, and efficacy in patients with recurrent or metastatic triple-negative-type breast cancer, who have received anthracycline and taxane agents
Title of the study (Brief title)	A Phase I/II study of olaparib in combination with eribulin mesylate in patients with TNBC
Region	Japan

Condition
Condition	Breast cancer
Classification by specialty	Hematology and clinical oncology Breast surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	The safety, tolerability, and MTD of olaparib in combination with eribulin mesylate will be assessed, based on the incidence of dose limiting toxicity at each dose level in Phase I. The efficacy and safety of the combination will be assessed, in Phase II.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase I,II

Assessment
Primary outcomes	Phase I: Safety and tolerability Phase II: Response rates
Key secondary outcomes

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Eribulin mesylate administer day 1, day 8, tri-weekly interval. Olaparib administer continuously and/or intermittently according to in each cohort. The trial treatment will be continued until there is progressive disease.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	18 years-old <=
Age-upper limit	Not applicable
Gender	Female
Key inclusion criteria	1)Histological confirmation of invasive breast cancer 2)Unresectable clinical StageIIIB, IIIC or IV or eligible for systemic chemotherapy for recurrent breast cancer 3)Histological confirmation of breast cancer without overexpression of HER2 (0 or 1+ in immunohistocompatibility (IHC), or negative in in-situ hybridization (ISH) tests). 4)Histological confirmation of hormonal receptor-negative breast cancer (Allred score < 3 in the IHC test for estrogen receptor and progesterone receptor). 5)PS (ECOG) 0 to 1 6)A treatment history of anthracycline and taxane agents, irrespective of the type of combination or treatment order 7)Patients with the following values in their latest laboratory tests -Neutrophil count > 1,500/mm3 -Hemoglobin > 9.0/dL -Platelet count > 100,000/mm3 -Total bilirubin < 1.5 mg/dL -Serum AST/ALT < 100 IU/L -Serum creatinine < 1.2 mg/dL -ECG Normal or minimal changes not requiring treatment and QTc interval < 450 ms 8)Recovery to grade 0 or 1 from all toxicities related to chemotherapy and radiotherapy, except for stable grade 0 to 2 sensory neuropathy and alopecia
Key exclusion criteria	1)Pregnant or breast-feeding women, or women of child bearing potential who intend to become pregnant 2)Patients who received treatment (chemotherapy or study treatment) within 1 week from the last administration or underwent treatment procedures (surgery or exposure to radiation) within the 2 weeks preceding enrollment 3)Patients with respiratory failure requiring oxygen inhalation therapy 4)Patients requiring therapeutic dosages of warfarin or related agents 5)Patients with signs or symptoms of interstitial pneumonia or pulmonary fibrosis 6)Patients who are HBs antigen-positive, HCV antibody-positive and/or HIV antibody-positive (Patients who are HBV-DNA positive and/or HCV-RNA positive are cannot be allowed) 7)Patients with serious cardiovascular disease 8)Patients with diabetes mellitus associated with poor glycemic control or receiving insulin 9)Patients with metastases to brain 10)Patients with meningeal carcinomatosis 11)Patients with gastrointestinal obstruction or the symptoms of it 12)Patients with synchronous double cancer, not including lesions equivalent to carcinoma in situ or mucosal carcinoma considered healed with topical therapy 13)Patients who have no features suggestive of MDS/AML on peripheral blood smear 14)Patients receiving the following classes of CYP3A4 inhibitors and inducers -CYP3A4 inhibitors: Azole antifungals, Macrolide antibiotics, Protease inhibitors -CYP3A4 inducers: Phenytoin, Rifampicin, Carbamazepine, Barbiturate derivatives 15)Patients with history of treatment with or allergy to eribulin mesylate Patients with history of treatment with or allergy to PARP inhibitors
Target sample size	48

Research contact person
Name of lead principal investigator	Kan Yonemori
Organization	National Cancer Center Hospital
Division name	Breast and Medical Oncology Division
Address	5-1-1 Tsukiji, Chuo-ku, Tokyo104-0045, Japan
TEL	03-3542-2511
Email	Olaparib_trial_office@umin.ac.jp

Public contact
Name of contact person	Tamie Sukigara
Organization	National Cancer Center
Division name	Clinical Trial Support Office
Address	5-1-1 Tsukiji, Chuo-ku, Tokyo104-0045, Japan
TEL	03-3547-5201
Homepage URL
Email	Olaparib_trial_office@umin.ac.jp

Sponsor
Institute	National Cancer Center Hospital
Institute
Department

Funding Source
Organization	Japan Medical Association
Organization
Division
Category of Funding Organization	Non profit foundation
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	独立行政法人国立病院機構大阪医療センター（大阪府） 独立行政法人国立病院機構四国がんセンター（愛媛県） 独立行政法人国立病院機構北海道がんセンター（北海道） 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター（神奈川県） 千葉県がんセンター（千葉県） 独立行政法人国立がん研究センター中央病院（東京都）

Other administrative information
Date of disclosure of the study information	2012 Year 12 Month 10 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2012 Year 10 Month 05 Day
Anticipated trial start date	2013 Year 01 Month 22 Day
Last follow-up date	2016 Year 09 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2012 Year 12 Month 06 Day
Last modified on	2018 Year 03 Month 05 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011159