UMIN-CTR Clinical Trial

Public title

Asian, International, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Tamoxifen With or Without Palbociclib +/- Goserelin in Women with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer

Acronym

NCCH1607/ WI217662/ PATHWAY

Scientific Title

Asian, International, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Tamoxifen With or Without Palbociclib +/- Goserelin in Women with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer

Scientific Title:Acronym

NCCH1607/ WI217662/ PATHWAY

Region

Japan

Asia(except Japan)

Condition

breast cancer

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To demonstrate the superiority of palbociclib in combination with tamoxifen (with or without goserelin) over tamoxifen (with or without goserelin) alone in prolonging investigator assessed progression-free survival (PFS) in women with hormone receptor (HR) positive/HER2 negative advanced or metastatic breast cancer, regardless of their menopausal status.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Explanatory

Developmental phase

Phase III

Primary outcomes

Progression Free Survival (PFS) as assessed by the investigator

Key secondary outcomes

Overall Survival (OS)
1 year, 2 year, and 3 year survival probabilities
Objective Response (OR: CR or PR)
Duration of Response (DR)
Clinical Benefit Response (CBR: CR or PR or SD >=24 weeks)
Pharmacokinetics
Safety
Patient Reported Outcomes (PRO)

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

YES

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Control arm (Arm A)
Placebo orally once daily on Day 1 to Day 21 followed by 7 days off treatment for each 28 day cycle, plus tamoxifen 20 mg orally once daily (continuously).

Pre- and perimenopausal women must receive therapy with the LH-RH agonist goserelin (Zoladex or generic) 3.6 mg given every 4 weeks or a long acting form (LA) 10.8 mg given every 12 weeks, subcutaneously.

Interventions/Control_2

Investigational arm (Arm B)
Palbociclib 125 mg/day, orally once daily on Day 1 to Day 21 followed by 7 days off treatment for each 28 day cycle, plus tamoxifen 20 mg orally once daily (continuously).

Pre- and perimenopausal women must receive therapy with the LH-RH agonist goserelin (Zoladex or generic) 3.6 mg given every 4 weeks or a long acting form (LA) 10.8 mg given every 12 weeks, subcutaneously.

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

Female

Key inclusion criteria

1. Women 18 years of age or older at informed consent.
2. Histologically or cytologically proven diagnosis of breast cancer with evidence of locally advanced or metastatic disease, not amenable to resection or radiation therapy with curative intent.
3. Documentation of ER positive and/or PgR positive tumor (>=1% positive stained cells, or Allred score of 3 or more) based on most recent tumor biopsy utilizing an assay consistent with local standards.
4. Documented HER2 negative tumor based on local testing on most recent tumor biopsy utilizing an assay consistent with local standards.
5. Patients will be candidates to receive tamoxifen as first-line or second-line endocrine treatment for their advanced/metastatic disease.
6. Measurable disease or non-measurable disease as defined by RECIST ver.1.1.
7. Eastern Cooperative Oncology Group (ECOG) PS 0-1.
8. Adequate organ and marrow function defined as follows:
- ANC >=1,500/mm3 (1.5 x 10^9/L);
- Platelets >=100,000/mm3 (100 x 10^9/L);
- Hemoglobin >=9 g/dL (90 g/L);
- Serum creatinine >=1.5 x ULN or estimated creatinine clearance >=60 ml/min as calculated using the method standard for the institution;
- Total serum bilirubin <=1.5 x ULN (<=3.0 x ULN if Gilbert's disease);
- AST and/or ALT <=3 x ULN (<=5.0 x ULN if liver metastases present);
- Alkaline phosphatase <=2.5 x ULN (<=5.0 x ULN if bone or liver metastases present).
9. Resolution of all adverse effects of prior therapy or surgical procedures to National Cancer Institute (NCI) CTCAE ver.4.0 Grade <=1 (except alopecia).
10. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study.
11. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Key exclusion criteria

1. Prior treatment with any CDK inhibitor, or tamoxifen (patients who progressed >12 months after the completion of adjuvant therapy with tamoxifen are eligible), or with everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway.
2. Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of life threatening complications in the short term ("visceral crisis").
3. Known active uncontrolled or symptomatic Central Nervous System metastases.
4. Current use of food or drugs known to be strong or moderate CYP3A4 and/or CYP2D6 inhibitors, strong or moderate CYP3A4 inducers, and drugs that are known to prolong the QT interval.
5. Patients who received other SERM or hormone replacement therapy within 12 months prior to randomization.
6. Major surgery, chemotherapy, endocrine therapy, radiotherapy, or other anti-cancer therapy within 2 weeks before randomization. Patients who received prior radiotherapy to >=25% of bone marrow.
7. Any other malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the esophagus, stomach, colon or cervix.
8. QTc interval >480 msec, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
9. Cardiovascular disorder within 6 months prior to randomization.
10. Impairment of gastro intestinal (GI) function or GI disease.
11. Prior hematopoietic stem cell or bone marrow transplantation.
12. Known abnormalities in coagulation.
13. Known or possible hypersensitivity to tamoxifen, goserelin, any of their excipients or to any palbociclib/placebo excipients.
14. Known human immunodeficiency virus infection.
15. Patients who are pregnant or lactating. Patients who are unwilling or unable to use contraception.
16. Participation in other studies involving investigational drug(s) within 4 weeks before randomization.

Target sample size

180

Name of lead principal investigator

1st name	Kan
Middle name
Last name	Yonemori

Organization

National Cancer Center Hospital

Division name

Department of Breast and Medical Oncology

Zip code

104-0045

Address

5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

TEL

03-3542-2511

Email

NCCH1607_office@ml.res.ncc.go.jp

Name of contact person

1st name	Tomomi
Middle name
Last name	Hata

Organization

National Cancer Center Hospital

Division name

Clinical Reseach Support Office

Zip code

104-0045

Address

5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

TEL

03-3542-2511

Homepage URL

Email

NCCH1607_office@ml.res.ncc.go.jp

Institute

National Cancer Center Hospital

Institute

Department

Personal name

Organization

Pfizer Inc.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Pfizer Inc.
Korean Cancer Study Group (KCSG)

Name of secondary funder(s)

Organization

National Cancer Center Hospital IRB

Address

5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan

Tel

03-3542-2511

Email

NCC_IRBoffice@ml.res.ncc.go.jp

Secondary IDs

YES

Study ID_1

NCT03423199

Org. issuing International ID_1

ClinicalTrials.gov

Study ID_2

Org. issuing International ID_2

IND to MHLW

2020年5月29日（届出回数_11回）

Institutions

国立がん研究センター中央病院（東京都）、北海道がんセンター（北海道）、千葉県がんセンター（千葉県）、国立がん研究センター東病院（千葉県）、虎の門病院（東京都）、神奈川県立がんセンター（神奈川県）、愛知県がんセンター（愛知県）、大阪医療センター（大阪府）、近畿大学病院（大阪府）、兵庫県立がんセンター（兵庫県）、四国がんセンター（愛媛県）、九州がんセンター（福岡県）、Severance Hospital, Yonsei University Health System （韓国）、Seoul National University Hospital （韓国）、Asan Medical Center（韓国）、National Cancer Center（韓国）、Ajou University Hospital （韓国）、National Taiwan University Hospital（台湾）、 Sun Yat-Sen Cancer Center（台湾）、Taipei Veterans General Hospital（台湾）、 National Cancer Centre Singapore （シンガポール）、National University Hospital（シンガポール）

Date of disclosure of the study information

2018

Year

01

Month

15

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

185

Results

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

No longer recruiting

Date of protocol fixation

2017

Year

03

Month

30

Day

Date of IRB

2017

Year

10

Month

24

Day

Anticipated trial start date

2018

Year

02

Month

09

Day

Last follow-up date

2025

Year

09

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

01

Month

15

Day

Last modified on

2023

Year

11

Month

17

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034267