UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000030649 |
|---|---|
| Receipt number | R000034981 |
| Scientific Title | An Open Label Phase II Study on the efficacy of Nivolumab(ONO-4538) in Japanese Subjects with cancer of unknown primary (CUP) (NivoCUP) |
| Date of disclosure of the study information | 2018/02/01 |
| Last modified on | 2025/01/05 10:03:05 |
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Basic information
Public title
An Open Label Phase II Study on the efficacy of Nivolumab(ONO-4538) in Japanese Subjects with cancer of unknown primary (CUP) (NivoCUP)
Acronym
An Open Label Phase II Study on the efficacy of Nivolumab in Japanese Subjects with cancer of unknown primary (CUP) (NivoCUP)
Scientific Title
An Open Label Phase II Study on the efficacy of Nivolumab(ONO-4538) in Japanese Subjects with cancer of unknown primary (CUP) (NivoCUP)
Scientific Title:Acronym
An Open Label Phase II Study on the efficacy of Nivolumab in Japanese Subjects with cancer of unknown primary (CUP) (NivoCUP)
Region
| Japan |
Condition
Condition
Cancer of unknown primary
Classification by specialty
| Medicine in general | Hematology and clinical oncology |
Classification by malignancy
Malignancy
Genomic information
YES
Objectives
Narrative objectives1
To evaluate the efficacy of nivolumab for unknown primary cancer.
Basic objectives2
Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase
Phase II
Assessment
Primary outcomes
Overall response rate (Blinded independent central review) for previously treated subjects.
Key secondary outcomes
Overall response rate (Investigator's review) for previously treated subjects.
Overall response rate (Blinded independent central review) for whole subjects.
Disease control rate, overall survival, overall survival rate and progression free survival rate at 6, 12, 18, and 24 months, progression free survival, duration of response, time to response, best response, and change of tumor burden (Blinded independent central review and investigator's review).
Safety and feasibility of nivolumab for cancer of unknown primary.
Evaluation the association between efficacy of nivolumab and PD-L1 expression (cut off; 1%, 10%, 50%) or tumor infiltrated T lymphocytes (CD4,CD8,FOXP3).
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
biweekly 240mg nivolumab treatment
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
| 20 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
1.Subjects with histologically confirmed cancer of unknown primary site based on adequate investigation of primary sites (excludes subjects who were pathologically diagnosed with malignant melanoma, malignant lymphoma or sarcoma)
2.Treatment naive or previously treated with chemotherapy including platinum agents
3.Either a formalin-fixed, paraffin-embedded (FFPE) tissue block or tumor tissue sections obtained within 1 year must be submitted for biomarker evaluation
4. Men and women above 20-years of age
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
6. Expected more than 90 days survival
7. Measurable disease by CT or MRI per RECIST 1.1 criteria
8. SpO2 at room air is higher than 94% by pulse oximeter
9.Adequate laboratory data
ANC above; 1.5 X 109/L
Hemoglobin above; 8.0 mg/dL
Platelets above; 100 x 109/L
without the use of hematopoietic growth factors
Serum creatinine below; 1.5 X ULN
Creatinine clearance (Cockcroft/Gault assumption) above 45ml/min
Total bilirubin below; 1.5 X ULN
AST and ALT below; 3.0 X ULN
10. Women of childbearing potential must agree to follow instructions for methods of contraception from the time of enrollment for the duration of treatment with nivolumab plus 5 months post-treatment completion. Women must not be breastfeeding
11. Men who must agree to follow instructions for methods of contraception for the duration of treatment with nivolumab plus 7 months post-treatment completion
12. Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines
Key exclusion criteria
1.Indication for curative surgery or radiotherapy
2.Favorable subsets under treatable condition
3.Proven primary site before enrollment
4.History of allergy or hypersensitivity to drug components
5.Judged that the adverse events from the previous treatment influence on the study evaluation
6.Subjects with untreated CNS metastases
7.Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization
8.Prior therapy with drug targeting immune-checkpoint pathways
9.Subjects treated with any investigational drug within 28 days before initiation of the study treatment
10.Anti-cancer therapy within 14 days before enrollment
11.Subjects who were treated with radiotherapy within 28 days (palliative radiotherapy within 14 days) before enrollment
12.Subjects with diseases listed as below
-An active, chronic or recurrent autoimmune disease
-Interstitial lung disease
-Diverticulitis or symptomatic gastrointestinal ulcer disease
-Uncontrollable diabetes
-Uncontrollable pleural , ascites or pericardial effusion requiring treatment
-Stroke, cerebrovascular accident, thrombosis, or thromboembolism within 180 days before the enrollment
-Known history of HIV or AIDS
-Positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
-Systemic infection requiring treatment
-Uncontrolled or severe cardiovascular disease, congestive heart failure,
arrhythmias, pericardial disease or cardiac amyloidosis
-Uncontrolled intercurrent illness
13.Surgery requiring local or surface anesthesia within 14 days or general anesthesia within 28 days before the enrollment
14.Subjects with other active malignancy
15.History of organ transplantation or hematopoietic stem cell transplantation
16.Women who are pregnant or breast feeding
17.Subjects be in a state lacking consent ability
18.Subjects with unsuitable condition judged by principal investigator
Target sample size
55
Research contact person
Name of lead principal investigator
| 1st name | Kazuhiko |
| Middle name | |
| Last name | Nakagawa |
Organization
Kindai University, Faculty of Medicine
Division name
Department of Medical Oncology
Zip code
589-8511
Address
377-2 Ohno-higashi, Osaka-Sayama, 589-8511, Japan
TEL
072-366-0221
nakagawa@med.kindai.ac.jp
Public contact
Name of contact person
| 1st name | Junko Tanizaki, Hidetoshi Hayashi |
| Middle name | |
| Last name | Junko Tanizaki, Hidetoshi Hayashi |
Organization
Kindai University, Faculty of Medicine
Division name
Department of Medical Oncology
Zip code
589-8511
Address
377-2 Ohno-higashi, Osaka-Sayama, 589-8511, Japan
TEL
072-366-0221
Homepage URL
tanizaki_j@med.kindai.ac.jp
Sponsor or person
Institute
Kindai university, Faculty of Medicine, Department of Medical Oncology
Institute
Department
Personal name
Funding Source
Organization
ONO PHARMACEUTICAL CO., LTD
Organization
Division
Category of Funding Organization
Profit organization
Nationality of Funding Organization
Other related organizations
Co-sponsor
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Kindai university institutional Review Board
Address
377-2, Ohnohigashi, Osaka-sayama, Osaka, Japan
Tel
072-366-0221
NA
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
近畿大学（大阪府）、東北大学（宮城県）、埼玉医科大学国際医療センター（埼玉県）、千葉大学（千葉県）、虎の門病院（東京都）、神戸大学（兵庫県）、大阪市立総合医療センター（大阪府）、和歌山県立医科大学（和歌山県）広島市立広島市民病院（広島県）、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
| 2018 | Year | 02 | Month | 01 | Day |
Related information
URL releasing protocol
https://pubmed.ncbi.nlm.nih.gov/34843940/
Publication of results
Partially published
Result
URL related to results and publications
https://pubmed.ncbi.nlm.nih.gov/34843940/
Number of participants that the trial has enrolled
54
Results
Fifty-six patients with CUP were enrolled in the trial. For the 45 previously treated patients, objective response rate was 22.2% [95% confidence interval (CI), 11.2% to 37.1%], with a median progression-free survival and overall survival of 4.0 months (95% CI, 1.9-5.8 months) and 15.9 months (95% CI, 8.4-21.5 months), respectively.
Results date posted
| 2025 | Year | 01 | Month | 05 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Between 19 February 2018 and 9 August 2019, a total of 56 patients with CUP, including 45 previously treated and 11 previously untreated individuals, were enrolled at 10 sites in Japan. All enrolled patients were included in efficacy and safety analysis.
Participant flow
Between 19 February 2018 and 9 August 2019, a total of 56 patients with CUP, including 45 previously treated and 11 previously untreated individuals, were enrolled at 10 sites in Japan. All enrolled patients were included in efficacy and safety analysis.
Adverse events
Among all patients, including both previously treated and untreated, 53 (94.6%) individuals experienced AEs of any grade, with 34 (60.7%) experiencing AEs of grade 3 or 4. Serious AEs were observed in 27 (48.2%) patients, and 4 patients (7.1%) discontinued nivolumab because of AEs. No treatment-related death occurred
Outcome measures
For the 45 previously treated patients, objective response rate was 22.2% [95% confidence interval (CI), 11.2% to 37.1%], with a median progression-free survival and overall survival of 4.0 months (95% CI, 1.9-5.8 months) and 15.9 months (95% CI, 8.4-21.5 months), respectively. Similar clinical benefits were also observed in the 11 previously untreated patients.
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
No longer recruiting
Date of protocol fixation
| 2017 | Year | 12 | Month | 11 | Day |
Date of IRB
| 2018 | Year | 01 | Month | 23 | Day |
Anticipated trial start date
| 2018 | Year | 02 | Month | 19 | Day |
Last follow-up date
| 2020 | Year | 08 | Month | 09 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
Other
Other related information
Management information
Registered date
| 2017 | Year | 12 | Month | 31 | Day |
Last modified on
| 2025 | Year | 01 | Month | 05 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034981
