UMIN-CTR Clinical Trial

Public title

A multicenter phase II trial of the triplet antiemetic therapy with palonosetron, aprepitant and olanzapine for highly emetogenic chemotherapy in breast cancer.

Acronym

PATROL-II

Scientific Title

A multicenter phase II trial of the triplet antiemetic therapy with palonosetron, aprepitant and olanzapine for highly emetogenic chemotherapy in breast cancer.

Scientific Title:Acronym

PATROL-II

Region

Japan

Condition

breast cancer

Classification by specialty

Hematology and clinical oncology

Not applicable

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

Efficacy of antiemetic therapy with a combination of palonosetron (PALO), aprepitant (APR), and olanzapine (OLN) without steroids for patients with malignancies scheduled to receive initial treatment with highly emetogenic chemotherapy for breast cancer and safety in the phase II trial.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Total Control in overall phase

Key secondary outcomes

1 TC ratio in acute and late phase
2 Complete response of all period and acute phase, late phase
3 Complete control of all periods and acute and late stages
4 No nausea for all period and acute phase, late phase
5 Time to treatment failure (TTF)
6 adverse events

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

Palonosetron + Aprepitant + Olanzapine (5 mg)

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

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Patients with breast cancer
2) Patients who are over 20 years old at thetime of registration
3) The patients whom highly emetogenic chemotherapy for breast cancer is given in for the first time
4) Eastern Cooperative Oncology Group(ECOG) performance status(PS) of 0, 1 or 2
5) Patients who have adequate organ functions
<Each of the following values are examined within 2 weeks before registration for this study>
ALT < 100 U/L
AST < 100 U/L
T-Bil < 2.0 mg/dL
CCr >= 55 mL/min
6) Patients who got written informed consent prior to registration

Key exclusion criteria

1) Patients who has history of hypersensitivity or allergy for study drugs or similar compounds.
2) Patients taking systemic corticosteroid (oral and intravenous) except for
inhaled or topical corticosteroid preparation
3) Patients having a clear vomiting symptom such as brain metastasis or gastrointestinal obstruction to the passage of foods
4) Patients with symptomatic ascites or pleural effusions requiring therapeutic puncture
5) Patients with obstruction of gastrointestinal tract, for example gastric outlet or ileus etc.
6) Patients who have convulsive disorders requiring anticonvulsants therapy
7) Patients receieving adrenaline or pimozide
8) Patients who start taking opioids within 48 h prior to registration
9) Patients who received radiation therapy to abdomen or pelvis within 6 days prior to registration or will receive radiation therapy until 6 days after cisplatin administration
10) Patients regularly taking antiemetics other than study drugs
11) Pregnant, breastfeeding or expecting women or who do not wish to use contraception
12) Patients with diabetes mellitus receiving treatment of antidiabetic agents or having HbA1c (NGSP) 6.5 or more,
or HbA1c (NGSP) in less than 28 days before registration is the patient with (in the case of JDS more than 6.1%) 6.5% or more.
13) Patients with smoking habit
14) The patients who have difficulty in operation such as the input, and the like of EDC.
15) Patients who are judged to be inappropriate for the study by the investigator

Target sample size

89

Name of lead principal investigator

1st name	Toshihiro
Middle name
Last name	Hama

Organization

Japanese Foundation for Cancer Reseach
Cancer Institute Hospital

Division name

Department of Pharmacy

Zip code

135-8550

Address

3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan

TEL

03-3520-0111

Email

toshihiro.hama@jfcr.or.jp

Name of contact person

1st name	Kenichi
Middle name
Last name	Suzuki

Organization

Hoshi University

Division name

Division of Applied Pharmaceutical

Zip code

142-8501

Address

Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan

TEL

03-5498-6241

Homepage URL

Email

kenichi-suzuki@hoshi.ac.jp

Institute

Hoshi University
Division of Applied Pharmaceutical

Institute

Department

Personal name

Organization

University of Shizuoka, School of Pharmaceutical Sciences

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Japanese Foundation for Cancer Reseach Cancer Institute Hospital

Address

3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan

Tel

03-3520-0111

Email

med.shinsa@jfcr.or.jp

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

2019

Year

11

Month

20

Day

URL releasing protocol

Protocol not listed

Publication of results

Published

URL related to results and publications

https://www.nature.com/articles/s41598-024-79781-6

Number of participants that the trial has enrolled

84

Results

The primary endpoint was below the threshold and we could not find any benefit in the dexamethasone-free regimen.

The CR rate was also examined as one of the secondary endpoints, with similar results.

Although dexamethasone is considered to have side effect concerns, its effect on CINV cannot be ignored, suggesting that easy complete omission should be avoided.

Results date posted

2024

Year

12

Month

16

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The median age was 51 years (range:29 71), all patients were female, and the performance status (PS) was 0 for all cases. Comparisons between premenopausal and postmenopausal patients were 46 (54.8%) versus 38 (45.2%). The regimens consisted of 32 cases of EC (38.1%), 32 cases of dose dense EC (38.1%), 18 cases of AC (21.4%), and 2 cases of FEC (2.4%).

Participant flow

The inclusion criteria were breast cancer, highly emetogenic chemotherapy based on anthracycline or cyclophosphamide, age of 20 years or older, ECOG PS 0-2, and adequate organ function. After enrollment, patients underwent blood sampling on the treatment day and reported their CINV symptoms through an electronic data capture (EDC) system on their personal devices for 120 hours following administration.

Adverse events

In this study, there were 84 evaluable patients for safety assessment. There were no treatment discontinuations due to adverse events, and no unexpected severe adverse events related to antiemetic drugs occurred during the observation phase. The most common treatment-related adverse events were anorexia and constipation. Most adverse events were Grade 2 or lower, with only one each of Grade 3 anorexia and somnolence. Somnolence, considered to be due to OLN, was reported in 38.1% of cases (Table 3). In addition to adverse event assessment by medical staff using CTCAE ver5.0, patient-reported adverse event assessment based on PRO-CTCAE version 1.0 was conducted20. Patients were evaluated for adverse events related to symptoms experienced in the past 7 days, categorized by adverse event category, and rated on a 5-point scale on the day before chemotherapy initiation (day 0) and on the 7th day of treatment initiation (day 7). Subsequently, the difference in adverse event reporting before and after treatment was calculated using the subtraction method of baseline values17, and an overall grade was calculated by comparing PRO-CTCAE descriptions. In the assessment by PRO-CTCAE, the frequency of adverse events generally exceeded that of medical staff evaluations. Similarly, in the evaluation by PRO-CTCAE, there was a higher proportion of Grade 3 or higher adverse events, and Grade 4 was observed for five items except for insomnia.

Outcome measures

Loss of appetite 52.4%, constipation 50%, diarrhea 19%, hiccups 17.9%, drowsiness 38.1%, insomnia 6%.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2019

Year

05

Month

01

Day

Date of IRB

2019

Year

10

Month

16

Day

Anticipated trial start date

2019

Year

12

Month

10

Day

Last follow-up date

2022

Year

06

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2019

Year

11

Month

20

Day

Last modified on

2024

Year

12

Month

16

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042017