Immunotherapy, Hormone Therapy, and AKT Inhibitor for Premenopausal ER Positive MBC

NCT05720260 | Recruiting Phase 2 DMC

• 1 other identifier: 202109031MIPD
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Premenopausal Breast Cancer; Metastatic Breast Cancer; ER Positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  PFS comparison between historical control (fulvestrant and goserelin) and Arm A/B/C

  From time of randomization to death or tumor progression whichever comes first in 200 months

Study Arms (3)

Arm A: goserelin/ fulvestrant/ durvalumab

EXPERIMENTAL

Historical control arm (goserelin, fulvestrant) plus immunotherapy

Drug: Goserelin; Drug: Fulvestrant; Drug: Durvalumab

Arm B: goserelin/ fulvestrant/ capivasertib/ durvalumab

EXPERIMENTAL

Historical control arm (goserelin, fulvestrant) plus AKT inhibitor and immunotherapy

Drug: Goserelin; Drug: Fulvestrant; Drug: Capivasertib; Drug: Durvalumab

Arm C: goserelin/ fulvestrant/ capivasertib

EXPERIMENTAL

Historical control arm (goserelin, fulvestrant) plus AKT inhibitor and immunotherapy

Drug: Goserelin; Drug: Fulvestrant; Drug: Capivasertib

Interventions

Goserelin DRUG

Hormone therapy

Also known as: GnRH agonist

Arm A: goserelin/ fulvestrant/ durvalumab; Arm B: goserelin/ fulvestrant/ capivasertib/ durvalumab; Arm C: goserelin/ fulvestrant/ capivasertib

Fulvestrant DRUG

Hormone therapy

Also known as: SERD

Arm A: goserelin/ fulvestrant/ durvalumab; Arm B: goserelin/ fulvestrant/ capivasertib/ durvalumab; Arm C: goserelin/ fulvestrant/ capivasertib

Capivasertib DRUG

AKT inhibitor

Also known as: AZD5363

Arm B: goserelin/ fulvestrant/ capivasertib/ durvalumab; Arm C: goserelin/ fulvestrant/ capivasertib

Durvalumab DRUG

immunotherapy

Also known as: Imfinzi

Arm A: goserelin/ fulvestrant/ durvalumab; Arm B: goserelin/ fulvestrant/ capivasertib/ durvalumab

Eligibility Criteria

• Age: 20 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A histological confirmed ER positive (\>1%) invasive breast cancer.
• Locally advanced or metastatic disease with at least one measurable target lesion
• Patients who had not received chemotherapy for locally advanced or metastatic disease
• 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)
• 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.
• ECOG 0-1
• 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.

You may not qualify if:

• Patients fulfilled ANY of the following criteria will be excluded from this trial:
• Prior therapy with capivasertib, fulvestrant, anti-PD1 or anti-PDL1 immunotherapy
• Prior chemotherapy for locally advanced or metastatic breast cancer.
• Radiotherapy with a wide field of radiation within 4 weeks before the first dose of study treatment
• The tumor is HER-2 positive by IHC 3+ or IHC 2+/ISH positive.
• 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
• Other malignancy within 5 years except cured basal cell or squamous cell skin cancer or carcinoma in situ of the cervix.
• Psychiatric illness or social situation that would preclude study compliance.
• Serious non-healing wound, ulcer, or bone fracture.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment.
• Prior minor surgery within 7 days.
• History of allergic reaction to compounds of similar chemical composition to the study drugs.
• Pregnancy or lactation.
• With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment
• 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.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

Department of Oncology, National Taiwan University Hospital

Taipei, 100, Taiwan

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Goserelin; Gonadotropin-Releasing Hormone; Fulvestrant; capivasertib; durvalumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Study Officials

• Yen-Shen Lu, MD, PhD

  NTUH

  STUDY CHAIR

Central Study Contacts

Yen-Shen Lu, MD, PhD

CONTACT

+886-2-23123456; yslu@ntu.edu.tw

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2023
• First Posted: February 9, 2023
• Study Start: January 17, 2023
• Primary Completion: December 31, 2024
• Study Completion (Estimated): January 31, 2027
• Last Updated: June 10, 2024

Record last verified: 2024-04

Locations

TW (1)