UMIN-CTR Clinical Trial

Public title

A phase II trial of Down staging Chemotherapy with Nab-paclitaxel plus Gemcitabine in patients with locally advanced pancreatic cancer

Acronym

A phase II trial of GnP down staging chemotherapy for patients with locally advanced pancreatic cancer (CAP-005)

Scientific Title

A phase II trial of Down staging Chemotherapy with Nab-paclitaxel plus Gemcitabine in patients with locally advanced pancreatic cancer

Scientific Title:Acronym

A phase II trial of GnP down staging chemotherapy for patients with locally advanced pancreatic cancer (CAP-005)

Region

Japan

Condition

locally advanced pancreatic cancer

Classification by specialty

Hepato-biliary-pancreatic surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To estimate the effectiveness and safety of down staging chemotherapy using the combination of gemcitabine and Nab-paclitaxel against initially borderline or unresectable locally advanced pancreatic cancer.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

R0 resection rate

Key secondary outcomes

resection rate (R0+1), overall survival, disease free survival, pathological chemotherapy effect, adverse events, complication rate, tumor marker, tumor response rate, relative dose intensity, rate of protocol achievement, recurrence type, positive rate of lymph node

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

1)Down staging chemotherapy: 3 course of gemcitabine and nab-PTX combination therapy (21days for one course:day1, day8 nab-PTX:125mg/m2/day+GEM:1000mg/m2/day) or total six time administration
2)Surgical resection
3)Adjuvant therapy: 4 course of S-1 monotherapy (42days for one course:day1-28 S-1 80mg/m2)

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

Age-lower limit

20

years-old

<=

Age-upper limit

80

years-old

>

Gender

Male and Female

Key inclusion criteria

1)Invasive ductal carcinoma or invasive intraductal papillary-mucinors carcinoma proved by Radiological examination (enhanced CT or MRI)
2)No distant metastasis
3)Borderline or unresectable locally advanced pancreatic cancer
tumor abutment of the SMA, HA, CEA
tumor involving PV or SMV (diameter of encased PV or SMV are less than 50% of adjacent normal PV or SMV diameter.
4)patients who can tolerate the pancreatic surgery.
5)Age more than 20 or less than 80
6)No history of primary chemo therapy and/or radiation therapy.
7)ECOG performance status 0-1
8)Adequate organ function
9)Without problems for oral medication
10)Written informed consent

Key exclusion criteria

1)History of sever allergic reaction with gemcitabine, nab-paclitaxel or S-1
2)Pregnant females, possibly pregnant females, females wishing to become pregnant, and females feeding babies.
3)Pulmonary fibrosis or interstitial pneumonia
4)History of breast or lung radiation
5)Active infection
6)Patients with pleural effusion
7)Active double cancer
8)Patients with positive for HBs antigen
9)Patients under treatment with phenytoin or walfarin
10)Uncontrolled heart diseases such as angina, myocardial infarction within three months, and cardiac dysfunction
11)Uncontrolled diabetes or hypertension
12)Sever mental disorder
13)Inadequate physical condition, as diagnosed by primary physician

Target sample size

40

Name of lead principal investigator

1st name	Masayuki
Middle name
Last name	Ohtsuka

Organization

Chiba unviersity, Graduate School of Medicine

Division name

Department of General Surgery

Zip code

260-8677

Address

1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, JAPAN

TEL

81-43-222-7171

Email

otsuka-m@faculty.chiba-u.jp

Name of contact person

1st name	Shigetsugu
Middle name
Last name	Takano

Organization

Chiba unviersity, Graduate School of Medicine

Division name

Department of General Surgery

Zip code

260-8677

Address

1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, JAPAN

TEL

81-43-222-7171

Homepage URL

Email

stakano@faculty.chiba-u.jp

Institute

Chiba study group of adjuvant chemotherapy for pancreatic cancer

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Clinical Research Center, Chiba University Hospital

Address

1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, JAPAN

Tel

81-43-222-7171

Email

chibacrc@mac.com

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

2016

Year

05

Month

08

Day

URL releasing protocol

None

Publication of results

Unpublished

URL related to results and publications

None

Number of participants that the trial has enrolled

40

Results

A phase II trial of Down staging Chemotherapy with nabPTX plus Gemcitabine in patients with locally advanced pancreatic cancer was conducted. Of all 40 participants, the G3/4 toxicity was occurred in 19 patients (47.5%). In terms of hematological toxicity, neutropenia was commonly noted for grade 3/4 (37.5%) events. In terms of efficacy of down-staging GnP therapy, R0 resection rate was 55.0% in the FAS, 77.8% in the resected cases, and 87.0% in the on-protocol cohort.

Results date posted

2023

Year

04

Month

03

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Among all 40 participants, they were 24 men (60%), the mean age was 65 years, and 25 patients (62%) showing the primary tumor located in the head of the pancreas.

Participant flow

This trial enrolled 40 patients between May 2016 and Dec 2019.
The follow up period of the trial was finished in June 2022. The trial was finalized in Dec 2022.
(1) All participants in this study (ITT FAS 40cases)
(2) Target cohort that meets the protocol (PPS 37cases)
(3) The resected cases (27cases)
(4) Cases that completed the protocol (23cases)

Adverse events

Of the 40 patients who started neoadjuvant treatment, 24
(62%) completed the planned 3 cycles of GnP chemotherapy.
All patients were assessable for adverse events. One patient (2.5%) died due to sepsis with liver abscess infected by clostridium perfringens. The G3/4 toxicity was occurred in 19 patients (47.5%). In terms of hematological toxicity, neutropenia was commonly noted for grade 3/4 (n = 15; 37.5%) events. Increase of liver enzyme was occurred in 7.5%. Severe non-hematological toxicity (CG3) was infrequent, namely, diarrhea (2.5%) and fatigue (2.5%).

Outcome measures

Primary outcomes
R0 resection rate: (1) 22/40 (55.0%) in the FAS (3) 21/27 (77.8%) in the resected cases (4) 20/23 (87.0%) for on-protocol
Secondary outcomes
resection rate (R0/1) (1) 28/40 (70%) (3) 27/27 (100%) (4) 23/23 (100%)
median survival time (MST) of overall survival: (1) 26.6 months (3) 39.8 months (4) 39.8 months
MST of progression free survival: (1) 16.7 months
MST of disease free survival: (3) 16.9 months (4) 16.4 months
pathological chemotherapy effect: Evans grade
(3) I: 37.0%, IIa: 48.2%, IIb: 11.1%, III: 0%, IV: 3.7%
(4) I: 39.1%, IIa: 47.8%, IIb: 8.7%, III: 0%, IV: 4.4%
adverse events: 1 missing case, Sepsis (Liver abscess with cholangitis due to infection of clostridium perfringens)
complication rate (G3/4): 19/40 (47.5%)
tumor marker: normalization rate of CA19-9: (4) 43.5%
tumor response rate (RR): (1) 15/40 (37.5%) (3) 14/27 (51.9%) (4) 14/23 (60.9%)
the rate of tumor shrinkage (mean): (3) 72.3%, (4) 68.6%
relative dose intensity: (4) Gem 97.5%, nab-PTX 97.4%
rate of protocol completion: (4) 23/40 (57.5%)
positive rate of lymph node: (3) 20/27 (74.1%) (4) 17/23 (73.9%)

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2016

Year

05

Month

04

Day

Date of IRB

2016

Year

05

Month

04

Day

Anticipated trial start date

2016

Year

05

Month

23

Day

Last follow-up date

2022

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2016

Year

05

Month

08

Day

Last modified on

2023

Year

04

Month

03

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000025621