UMIN-CTR Clinical Trial

Public title

Phase 1/2 Clinical Study of S-488410 Multipeptide Cancer Vaccine in Patients with Advanced or Recurrent Esophageal Squamous Cell Carcinoma

Acronym

Phase 1/2 Clinical Study of S-488410 in Patients with Advanced or Recurrent Esophageal Squamous Cell Carcinoma

Scientific Title

Phase 1/2 Clinical Study of S-488410 Multipeptide Cancer Vaccine in Patients with Advanced or Recurrent Esophageal Squamous Cell Carcinoma

Scientific Title:Acronym

Phase 1/2 Clinical Study of S-488410 in Patients with Advanced or Recurrent Esophageal Squamous Cell Carcinoma

Region

Japan

Condition

Esophageal squamous cell carcinoma

Classification by specialty

Medicine in general	Gastroenterology	Surgery in general
Gastrointestinal surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To evaluate the safety, tolerability, and efficacy of S-488410 multipeptide cancer vaccine in patients with advanced or recurrent esophageal squamous cell carcinoma.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase I,II

Primary outcomes

Phase I
Term, severity, and incidence of adverse events and adverse drug reactions
Phase II
The rate of Cytotoxic T lymphocyte (CTL) induction

Key secondary outcomes

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Dose comparison

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

3

Purpose of intervention

Treatment

Type of intervention

Medicine

Vaccine

Interventions/Control_1

S-488410 (1 mg each of S-488401, S-488402, and S-488403) is subcutaneously administered weekly to the neck, armpit, or groin of the patients.

Interventions/Control_2

S-488410 (2 mg each of S-488401, S-488402, and S-488403) is subcutaneously administered weekly to the neck, armpit, or groin of the patients.

Interventions/Control_3

S-488410 (4 mg each of S-488401, S-488402, and S-488403) is subcutaneously administered weekly to the neck, armpit, or groin of the patients.

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

80

years-old

>

Gender

Male and Female

Key inclusion criteria

Patients meeting all of the following criteria will be included:
1)Patients with advanced or recurrent esophageal carcinoma
2)Patients who do not respond to standard chemotherapy (treatment including a fluorinated pyrimidine anticancer drug, platinum-containing drug, taxane anticancer drug) or are unable to continue treatment due to an adverse drug reaction
3)Patients who were histologically diagnosed as squamous cell carcinoma
4)Patients with a primary tumor or metastasis confirmed by imaging within 4 weeks before enrollment
5)Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 within 2 weeks before enrollment
6)Patients expected to have life prognosis at least 3 months after enrollment

Key exclusion criteria

Patients meeting any of the following criteria will be excluded:
1)Patients with multiple primary cancer (other than a non-melanoma skin cancer or cervical epithelial cancer)
2)Patients currently receiving or scheduled to receive during the study any antineoplastic agent, immunosuppressant, adrenocortical steroid, radiation therapy, immunotherapy, heat therapy, or surgery
3)Patients with substantial tumor invasion in the trachea
4)Patients with an autoimmune disease
5)Patients positive for anti-HIV antibody or antigen within 2 weeks before enrollment
6)Patients whose prior therapy for the primary disease has not concluded (final day of drug or radiation treatment) within 4 weeks before enrollment
7)Patients with a marrow function, hepatic function, or renal function test value meeting any of the following criteria in laboratory tests performed within 2 weeks before enrollment
- White blood cell count: < 2000/mm3 or > 15000/mm3
- Platelet count: < 50000/mm3
- AST and ALT: > 5-fold the upper limit of the standard range of the study center
- Total bilirubin: > 3-fold the upper limit of the standard range of the study center
- Serum creatinine: > 3-fold the upper limit of the standard range of the study center
8)Patients who are pregnant, may be pregnant, or are lactating woman
9)Patients who are unable or do not wish to engage in appropriate contraception from the time of enrollment to 12 weeks after the completion of treatment

Target sample size

96

Name of lead principal investigator

1st name
Middle name
Last name	Takuko Sawada

Organization

Shionogi & Co., Ltd.

Division name

GLOBAL DEVELOPMENT OFFICE

Zip code

Address

5-12-4, Sagisu, Fukushima-ku, Osaka

TEL

Email

Name of contact person

1st name
Middle name
Last name

Organization

Shionogi & Co., Ltd.

Division name

Corporate Communications Department

Zip code

Address

1-8, Doshomachi 3-chome, Chuo-ku, Osaka

TEL

Homepage URL

Email

Institute

Shionogi & Co., Ltd.

Institute

Department

Personal name

Organization

Shionogi & Co., Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2011

Year

03

Month

01

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

The rate of CTL induction as a primary endpoint was 82.4% for all HLA-A*24:02-positive patients receiving S-488410 (1, 2 or 4 mg). There was no dose-relationship in CTL induction as a primary endpoint and in objective response rate, disease control rate, progression free survival (PFS) and overall survival (OS) as secondary endpoints.
Among the patients with HLA-A*24:02, the OS was significantly longer in the patients with CTL induction than that in the patients without CTL induction.

Death, serious adverse events and AEs causing withdrawals observed in the phase 1 and phase 2 were mostly resulted from aggravation of primary disease (esophageal cancer), not due to side effect of S-488410.

The most frequent AE was injection site reaction but there was no patient who discontinued the treatment, suggesting that weekly subcutaneous dosing of S-488410 is well tolerated in patients with advanced or recurrent esophageal squamous cell carcinoma.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2010

Year

12

Month

10

Day

Date of IRB

Anticipated trial start date

2011

Year

03

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2011

Year

03

Month

01

Day

Last modified on

2017

Year

12

Month

12

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006127