Trial Title:
Immunotherapy, Hormone Therapy, and AKT Inhibitor for Premenopausal ER Positive MBC
NCT ID:
NCT05720260
Condition:
Premenopausal Breast Cancer
Metastatic Breast Cancer
ER Positive Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Durvalumab
Fulvestrant
Goserelin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Goserelin
Description:
Hormone therapy
Arm group label:
Arm A: goserelin/ fulvestrant/ durvalumab
Arm group label:
Arm B: goserelin/ fulvestrant/ capivasertib/ durvalumab
Arm group label:
Arm C: goserelin/ fulvestrant/ capivasertib
Other name:
GnRH agonist
Intervention type:
Drug
Intervention name:
Fulvestrant
Description:
Hormone therapy
Arm group label:
Arm A: goserelin/ fulvestrant/ durvalumab
Arm group label:
Arm B: goserelin/ fulvestrant/ capivasertib/ durvalumab
Arm group label:
Arm C: goserelin/ fulvestrant/ capivasertib
Other name:
SERD
Intervention type:
Drug
Intervention name:
Capivasertib
Description:
AKT inhibitor
Arm group label:
Arm B: goserelin/ fulvestrant/ capivasertib/ durvalumab
Arm group label:
Arm C: goserelin/ fulvestrant/ capivasertib
Other name:
AZD5363
Intervention type:
Drug
Intervention name:
Durvalumab
Description:
immunotherapy
Arm group label:
Arm A: goserelin/ fulvestrant/ durvalumab
Arm group label:
Arm B: goserelin/ fulvestrant/ capivasertib/ durvalumab
Other name:
Imfinzi
Summary:
This is an open-label randomized phase II study in estrogen receptor positive locally
advanced or metastatic breast cancer patients. The main inclusion population are either
luminal subtype B by PAM50 analysis or failed less than 2 lines of hormonal therapy for
locally advanced or metastatic breast cancer. The subjects have to be premenopausal or
perimenopausal and are not allowed to receive any systemic chemotherapy for their locally
advanced or metastatic breast cancer. Eligible subjects will be randomized into
goserelin/ fulvestrant/ durvalumab (Arm A), goserelin/ fulvestrant/ capivasertib/
durvalumab (Arm B), or goserelin/ fulvestrant/ capivasertib (Arm C) at a 1:1:1 ratio. The
primary endpoint is objective response rate (ORR) of the whole other three arm compared
to historical goserelin/ fulvestrantcontrol arm. The major secondary endpoint will be
progression-free survival or ORR compared among different treatment arms.
Detailed description:
This is an open-label randomized phase II study in estrogen receptor positive locally
advanced or metastatic breast cancer patients. The main inclusion population are either
luminal subtype B by PAM50 analysis or failed less than 2 lines of hormonal therapy for
locally advanced or metastatic breast cancer. The subjects have to be premenopausal or
perimenopausal and are not allowed to receive any systemic chemotherapy for their locally
advanced or metastatic breast cancer. Eligible subjects will be randomized into
goserelin/ fulvestrant/ durvalumab (Arm A), goserelin/ fulvestrant/ capivasertib/
durvalumab (Arm B), or goserelin/ fulvestrant/ capivasertib (Arm C) at a 1:1:1 ratio. The
primary endpoint is objective response rate (ORR) of the whole other three arm compared
to historical goserelin/ fulvestrant control arm. The major secondary endpoint will be
progression-free survival or ORR compared among different treatment arms. Secondary
endpoints include PFS and ORR comparison between arms. Exploratory endpoints include
biomarkers, such as TILs, PD-L1 correlation with treatment response.
Criteria for eligibility:
Criteria:
Inclusion criteria
1. A histological confirmed ER positive (>1%) invasive breast cancer.
2. Locally advanced or metastatic disease with at least one measurable target lesion
3. Patients who had not received chemotherapy for locally advanced or metastatic
disease
4. Patients have to be (i) either primary resistant to hormonal therapy defined as
recurrence developed within 2 years of adjuvant hormonal therapy (ii) or resistant
to prior hormonal therapy (failed ≤ 2lines of hormonal therapy for locally advanced
or metastatic breast cancer)
5. Patients must be premenopausal or perimenopausal women according the clinical
menstrual history or E2 / FSH level based on local hospital guidance. Patient with
menopausal status cannot be determined due to ongoing LHRH agonist treatment is
allowed if evidence of premenopausal status prior to patients' LHRH agonist usage
can be provided.
6. ECOG 0-1
7. Patients must have adequate organ and marrow reserve measured within 14 days(within
screening period ) prior to randomization as defined below:
- Hemoglobin ≥ 9.0 g/dL;
- Absolute neutrophil count ≥ 1,500 /L;
- Platelets ≥ 100,000/L;
- Total bilirubin ≤ 1.5 x upper normal limit;
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x upper normal limit; for patients with liver
metastases AST(SGOT)/ALT(SGPT) ≤ 5 x upper normal limit is allowed;
- Serum creatinine ≤ 1.5mg/dL or creatinine clearance ≧50ml/min;
- aPTT < 1.5 x upper normal limit (unless on therapeutic anti-coagulation);
- Proteinuria ≤ 1+ with urine dipstick, if > 1+, 24-hour urine protein must be ≤
1 g.
8. Age older than 20-year-old.
9. All women of childbearing potential must have a negative pregnancy test obtained
within 7 days before starting therapy. Patients must not be breastfeeding.
10. Patients with reproductive potential must use effective contraception (hormone or
barrier method of birth control) prior to study entry, for the duration of study
participation, and for 6 months after the completion of therapy.
11. Patients (or a surrogate) must be able to comply with study procedures and to give
signed informed consent, which includes compliance with the requirements and
restrictions listed in the informed consent form (ICF) and in the clinical study
protocol (CSP). The patients (or a surrogate) must be able to provide of signed and
dated written ICF prior to any mandatory study specific procedures, sampling, and
analyses.
12. Body weight >30 kg
13. Must have a life expectancy of at least 12 weeks Exclusion criteria
Patients fulfilled ANY of the following criteria will be excluded from this trial:
1. Prior therapy with capivasertib, fulvestrant, anti-PD1 or anti-PDL1 immunotherapy
2. Prior chemotherapy for locally advanced or metastatic breast cancer.
3. Radiotherapy with a wide field of radiation within 4 weeks before the first dose of
study treatment
4. The tumor is HER-2 positive by IHC 3+ or IHC 2+/ISH positive.
5. Patients have active brain metastases or spinal cord compression or brain metastases
unless asymptomatic, treated and stable and not requiring steroids for at least 4
weeks prior to start of study treatment
6. Other malignancy within 5 years except cured basal cell or squamous cell skin cancer
or carcinoma in situ of the cervix.
7. Psychiatric illness or social situation that would preclude study compliance.
8. Serious non-healing wound, ulcer, or bone fracture.
9. Major surgical procedure, open biopsy, or significant traumatic injury within 28
days prior to enrollment.
10. Prior minor surgery within 7 days.
11. History of allergic reaction to compounds of similar chemical composition to the
study drugs.
12. Pregnancy or lactation.
13. With the exception of alopecia, any unresolved toxicities from prior therapy greater
than CTCAE grade 1 at the time of starting study treatment
14. Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and TB testing in line with
local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),
hepatitis C. Patients with a past or resolved HBV infection (defined as the presence
of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients
positive for hepatitis C (HCV) antibody are eligible only if polymerase chain
reaction is negative for HCV RNA.
15. Known to have tested positive for human immunodeficiency virus
16. History of allogenic organ transplantation.
17. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease,
rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to
this criterion: a) Patients with vitiligo or alopecia; b) Patients with
hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement;
c)Any chronic skin condition that does not require systemic therapy; d) Patients
without active disease in the last 5 years may be included but only after
consultation with the study physician; e)Patients with celiac disease controlled by
diet alone.
18. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
situations that would limit compliance with study requirement, substantially
increase risk of incurring AEs or compromise the ability of the patient to give
written informed consent. Refractory nausea and vomiting, malabsorption syndrome,
chronic gastrointestinal diseases, inability to swallow the formulated product or
previous significant bowel resection, or other condition that would preclude
adequate absorption of capivasertib.
19. History of another primary malignancy except for: a) Malignancy treated with
curative intent and with no known active disease ≥5 years before the first dose of
IP and of low potential risk for recurrence; b) Adequately treated non-melanoma skin
cancer or lentigo maligna without evidence of disease; c)Adequately treated
carcinoma in situ without evidence of disease
20. History of leptomeningeal carcinomatosis.
21. Previous allogeneic bone marrow transplant or solid organ transplant.
22. Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
2. Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of
prednisone or its equivalent
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
23. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and
up to 30 days after the last dose of IP.
24. Any of the following cardiac criteria at screening:
- Mean resting corrected QT interval (QTc) >470 msec obtained from 3 consecutive
ECGs
- Any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG (eg, complete left bundle branch block, third degree heart block)
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, hypokalaemia, potential for Torsades de Pointes,
congenital long QT syndrome, family history of long QT syndrome or unexplained
sudden death under 40 years of age or any concomitant medication known to
prolong the QT interval
- Experience of any of the following procedures or conditions in the preceding 6
months: coronary artery bypass graft, angioplasty, vascular stent, myocardial
infarction, angina pectoris, congestive heart failure New York Heart
Association (NYHA) grade ≥2
- Uncontrolled hypotension - SBP <90 mmHg and/or DBP <50 mmHg
- Cardiac ejection fraction outside institutional range of normal or <50%
(whichever is higher) as measured by echocardiogram.
25. Clinically significant abnormalities of glucose metabolism as defined by any of the
following at screening:
- Patients with diabetes mellitus type I or diabetes mellitus type II requiring
insulin treatment
- HbA1c ≥8.0% (63.9 mmol/mol)
26. Any investigational agents or study drugs from a previous clinical study within 30
days of the first dose of study treatment
27. Potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of
study treatment (3 weeks for St John's wort), or sensitive substrates of CYP3A4,
CYP2C9 and/or CYP2D6 with a narrow therapeutic window within 1 week prior to the
first dose of study treatment.
28. Participation in another clinical study with an investigational medicinal product
(IMP) administered in the last 30 days or 5 half-lives, whichever is longer
29. History of hypersensitivity to active or inactive excipients of capivasertib,
fulvestrant, durvalumab, goserelin or drugs with a similar chemical structure or
class to the above-mentioned drugs
30. Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and
requirements.
Gender:
Female
Minimum age:
20 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Oncology, National Taiwan University Hospital
Address:
City:
Taipei City
Zip:
100
Country:
Taiwan
Status:
Recruiting
Contact:
Last name:
Yen-Shen Lu, MD, PhD
Phone:
886-2-23123456
Phone ext:
67009
Email:
yslu@ntu.edu.tw
Investigator:
Last name:
Yen-Shen Lu, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Chih-Hung Lin, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Dwan-Ying Chang, MD
Email:
Sub-Investigator
Investigator:
Last name:
Tom Wei-Wu Chen, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
I-Chun Chen, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Wei-Li Ma, MD
Email:
Sub-Investigator
Investigator:
Last name:
Ming-Yang Wang, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Po-Hsiang Huang, MD
Email:
Sub-Investigator
Investigator:
Last name:
Chia-Chen Li, MD
Email:
Sub-Investigator
Investigator:
Last name:
Ming-Han Yang, MD
Email:
Sub-Investigator
Start date:
January 17, 2023
Completion date:
January 31, 2027
Lead sponsor:
Agency:
National Taiwan University Hospital
Agency class:
Other
Source:
National Taiwan University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05720260
