Capivasertib Plus Fulvestrant vs. Fulvestrant in Primary High-risk Lobular Breast Cancer

NCT06607757 | Recruiting Phase 2 DMC

• 2 other identifiers: GBG118 - LOBSTER2023-509292-17-00
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 25

Brief Summary

This is a multicenter, prospective, open-label, randomized phase II study to evaluate the CCCA assessed by Ki67 drop below \<2.7% from baseline to week 2 (window of opportunity) and to week 10 with capivasertib plus fulvestrant compared with fulvestrant alone as neoadjuvant treatment for primary high-risk lobular breast cancer patients. 120 patients will be randomized to receive: \- Capivasertib (400 mg po twice daily d1-4 followed by 3 days off) for 2 weeks followed by capivasertib (400 mg po twice daily d1-4 followed by 3 days off) and fulvestrant (500 mg i.m. q28d, with an additional 500 mg dose given two weeks after the initial dose) for additional 8 weeks (overall 4 administrations of fulvestrant) or \- Fulvestrant (500mg i.m. q28d, with an additional 500 mg dose given two weeks after the core biopsy and the initial dose) for 10 weeks (overall 4 administrations) Treatment will be given until surgery/core-biopsy, disease progression, unacceptable toxicity, or withdrawal of consent of the patient. All patients will undergo core-biopsies, under treatment and after completing study therapy in order to assess Ki67%. Further treatment including surgery, (neo)adjuvant chemotherapy, radiotherapy, and (neo)adjuvant endocrine therapy will be administered at the discretion of the investigator and according to standard of care outside the clinical trial.

Conditions

CCCA Assessed by Ki67 Drop Below <2.7% From Baseline

Outcome Measures

Primary Outcomes (1)

• To assess complete cell cycle arrest (CCCA).

  The primary endpoint CCCA is defined as Ki67 drop to \&lt;2.7% after approximately 10 weeks (will be assessed centrally on the breast tissue submitted to central pathology)

  Up to 14 weeks

Secondary Outcomes (4)

• To asses safety and tolerability

  Up to 14 weeks

• To assess patholgogical complete response rate (pCR) by different definitions

  Up to 14 weeks

• To assess breast conservation rate (BCS)

  Up to 14 weeks

• To assess invasive disease-free survival (iDFS) and overall survival (OS)

  through study completion, an average of 2 years

Study Arms (2)

Arm A

EXPERIMENTAL

Capivasertib (400 mg po twice daily d1-4 followed by 3 days off) for 2 weeks followed by capivasertib (400 mg po twice daily d1-4 followed by 3 days off) and fulvestrant (500 mg i.m. q28d, with an additional 500 mg dose given two weeks after the initial dose) for additional 8 weeks (overall 4 administrations of fulvestrant)

Drug: Capivasertib; Drug: Fulvestrant injection

Arm B

ACTIVE COMPARATOR

Fulvestrant (500mg i.m. q28d, with an additional 500 mg dose given two weeks after the core biopsy and the initial dose) for 10 weeks (overall 4 administrations)

Drug: Fulvestrant injection

Interventions

Capivasertib DRUG

find arm A description

Also known as: Truqap

Arm A

Fulvestrant injection DRUG

find arm B description

Also known as: Faslodex

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and followup, and documented according to the local regulatory requirements.
• Postmenopausal women with age at diagnosis ≥ 18 years.
• Postmenopausal status is defined as:
• Age ≥60 years
• Age \<60 years and amenorrhea for at least 12 continuous months with no identified cause other than menopause
• Bilateral oophorectomy Negative pregnancy test (urine or serum) within 14 days prior to randomization for all postmenopausal women 50 years of age or younger without bilateral oophorectomy
• Willingness and ability to provide archived formalin fixed paraffin embedded (FFPE) tissue block from core biopsy before the start of neoadjuvant therapy.
• Centrally confirmed HER2-negative (IHC score 0-1+ or ISH negative according to ASCO/CAP guideline) and HR-positive (≥10% positive stained cells) disease, assessed on the core of diagnostic biopsy. Ki67% \>10% is required. In case of bilateral breast cancer, HER2-negative, HR-positive and lobular histology status has to be confirmed for both sides.
• Patients with invasive lobular breast cancer at high risk for recurrence defined as cT1c and clinical nodal involvement (cN+) or ≥ cT2 disease (irrespective of nodal involvement).
• No clinical evidence of distant metastases.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
• Estimated life expectancy of at least 5 years irrespective of the diagnosis of breast cancer.
• The patient must be accessible for scheduled visits, treatment, and followup.
• Normal cardiac function must be confirmed according to local guidelines.
• Laboratory requirements:

You may not qualify if:

• Female patients of childbearing potential.
• Excisional biopsy or lumpectomy performed prior to study entry.
• Surgical axillary staging procedure including sentinel lymph node biopsy prior to randomization. Exceptions: FNA or core biopsy of an axillary lymph node.
• Any previous treatment including endocrine therapy, chemotherapy, radiotherapy or targeted therapy (including AKT inhibitor or PIK3 inhibitor) for the currently diagnosed breast cancer.
• Concurrent use of herbal or natural products intended as treatment or prophylaxis for any type of cancer.
• Known hypersensitivity reaction to one of the compounds or substances used in this protocol.
• Potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort).
• Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of capivasertib.
• Any contraindication for fulvestrant.
• Patients with definitive clinical or radiologic evidence of stage IV cancer (metastatic disease) are not eligible.
• Patients with a history of any malignancy are ineligible with the following exceptions:
• Patient has been disease-free for at least 5 years and is at low risk for recurrence of that malignancy except for breast cancer.
• CIS of the cervix, basal cell and squamous cell carcinomas of the skin.
• History of type I or type II diabetes mellitus requiring insulin.
• Severe and relevant co-morbidity that would interact with the application of study drugs or the participation in the study, including cerebrovascular incident including transient ischemic attack, or symptomatic pulmonary embolism, active infection requiring intravenous anti-microbial treatment (antibiotics, anti-fungal, and anti-viral drugs) within 1 week of enrolment. Patients with confirmed Gilbert's syndrome may be included in the study.

Sponsors & Collaborators

• GBG Forschungs GmbH: lead
• AstraZeneca: collaborator

Study Sites (25)

Haematologie-Onkologie im Zentrum MVZ GmbH

Augsburg, 86150, Germany

RECRUITING

Charité

Berlin, 10117, Germany

ACTIVE NOT RECRUITING

Onkologische Schwerpunktpraxis - Studiengesellschaft Onkologie Bielefeld GbR

Bielefeld, 33604, Germany

RECRUITING

Hämato-Onkologie im Medicum - Onkologie und Hämatologie

Bremen, 28209, Germany

ACTIVE NOT RECRUITING

Kliniken der Stadt Köln GmbH - Brustzentrum Köln-Holweide

Cologne, 51067, Germany

ACTIVE NOT RECRUITING

Carl-Thiem-Klinikum gGmbH - Frauenklinik

Cottbus, 03048, Germany

ACTIVE NOT RECRUITING

Kath. St. Paulus GmbH - Klinische Forschung

Dortmund, 44137, Germany

ACTIVE NOT RECRUITING

Universitätsklinikum Essen - Klinik für Frauenheilkunde und Geburtshilfe

Essen, 45147, Germany

RECRUITING

Klinikum Frankfurt Höchst GmbH - Klinik für Gynäkologie und Geburtshilfe

Frankfurt am Main, 65929, Germany

ACTIVE NOT RECRUITING

Praxis für Interdisziplinäre Onkologie & Hämatologie

Freiburg im Breisgau, 79110, Germany

ACTIVE NOT RECRUITING

Mammazentrum Hamburg - am Krankenhaus Jerusalem

Hamburg, 20357, Germany

RECRUITING

Universitätsklinikum des Saarlandes - Frauenklinik

Homburg, 66424, Germany

ACTIVE NOT RECRUITING

Klinikum Kassel GmbH - Frauenklinik

Kassel, 34125, Germany

NOT YET RECRUITING

St. Elisabethen-Krankenhaus gGmbH - Senologie / Brustzentrum

Leipzig, 04277, Germany

RECRUITING

Medizinisches Versorgungszentrum MediaVita GmbH Muenster

Münster, 48145, Germany

RECRUITING

Klinikum Oldenburg AöR - Universitätsklinik für Innere Medizin - Onkologie

Oldenburg, 26133, Germany

ACTIVE NOT RECRUITING

MVZ für Hämatolgie und Onkologie Ravensburg GmbH - Studienzentrum

Ravensburg, 88212, Germany

ACTIVE NOT RECRUITING

Klinikum Südstadt - Universitätsfrauenklinik

Rostock, 18059, Germany

ACTIVE NOT RECRUITING

Leopoldina-Krankenhaus der Stadt Schweinfurt - Frauenklinik

Schweinfurt, 97422, Germany

RECRUITING

Johanniter-Krankenhaus Genthin-Stendal - Klinik für Frauenheilkunde und Geburtshilfe

Stendal, 39576, Germany

ACTIVE NOT RECRUITING

Kreiskrankenhaus Torgau - Gynäkologie

Torgau, 04860, Germany

ACTIVE NOT RECRUITING

Praxisnetzwerk Haematologie und internistische Onkologie Ueberoertliche Berufsausuebungsgemeinschaft - Hämatologie und Onkologie

Troisdorf, 53840, Germany

ACTIVE NOT RECRUITING

Marienhospital Witten - Brustzentrum

Witten, 58452, Germany

ACTIVE NOT RECRUITING

Klinikum Worms gGmbH - Frauenklinik

Worms, 67550, Germany

RECRUITING

Helios Klinikum Wuppertal GmbH - Landesfrauenklinik

Wuppertal, 42283, Germany

RECRUITING

Related Publications (1)

• Rugo HS, Oliveira M, Howell SJ, Dalenc F, Cortes J, Gomez HL, Hu X, Jhaveri KL, Krivorotko P, Loibl S, Morales Murillo S, Nowecki Z, Okera M, Park YH, Sohn J, Toi M, Iwata H, Yousef S, Zhukova L, Logan J, Twomey K, Khatun M, D'Cruz CM, Turner NC. Capivasertib and fulvestrant for patients with hormone receptor-positive advanced breast cancer: characterization, time course, and management of frequent adverse events from the phase III CAPItello-291 study. ESMO Open. 2024 Sep;9(9):103697. doi: 10.1016/j.esmoop.2024.103697. Epub 2024 Sep 5.

  PMID: 39241495 BACKGROUND

Related Links

• GBG Website with information about LOBSTER Trial

MeSH Terms

Interventions

capivasertib; Fulvestrant

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Sibylle Loibl, Prof. Dr. med.

  ESMO, ASCO, AGO Kommission Mamma (member); Goethe University Frankfurt; GBG Forschungs GmbH

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christina Müller-Weisbrod

CONTACT

+49610274800; LOBSTER@gbg.de

Study Design

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

Model Details: Evaluation of treatment outcome

Study Record Dates

• First Submitted: June 14, 2024
• First Posted: September 23, 2024
• Study Start: December 4, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: April 2, 2025

Record last verified: 2025-03

Locations

DE (25)