Neoadjuvant Chemo-endocrine Therapy and Immunotherapy for Pre-menopausal Luminal B Breast Cancer Patients

NCT04659551 | Completed Phase 2

• 2 other identifiers: GIADA Trial2016-004665-10
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 5

Brief Summary

Multicentric, phase II neoadjuvant trial in hormone-positive, HER-negative, luminal B, premenopausal breast cancer patients stage II-IIIA. Patients receive as neoadjuvant treatment before surgery: three courses of anthracycline-based chemotherapy followed by exemestane p.o. daily plus nivolumab i.v. 2-weekly for 8 courses. GnRH analogues are started concomitantly with chemotherapy and maintained until the completion of neoadjuvant treatment.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• pathological complete response (pCR)

  ypT0ypN0

  up to 7 months from enrolment

Secondary Outcomes (5)

• clinical objective response

  up to 6 months from enrolment

• molecular response

  up to 7 months from enrolment

• Breast conserving surgery

  up to 7 months from enrolment

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  up to 100 days from last nivolumab dose

• Correlative biomarkers

  Tumor samples will be collected at baseline, at 14 days after completion of anthracycline-based chemotherapy (about 7 weeks after first dose of Epirubicin), at surgery (about 30 weeks after first dose of Epirubicin)

Study Arms (1)

Arm 1

EXPERIMENTAL

Epirubicin 90 mg/mq + Cyclophosphamide 600 mg/mq i.v. every 3 weeks for 3 courses, followed by Nivolumab (240 mg flat dose i.v. each 2 weeks) for 8 courses plus exemestane 25 mg (orally, continuous daily dose, to be continued until surgery). LHRH analogue (Triptorelin 3.75mg 1 fl i.m. every 28 days) started concomitantly to anthracycline based chemotherapy, to be continued until surgery.

Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Triptorelin; Drug: Exemestane; Drug: Nivolumab

Interventions

Epirubicin DRUG

Epirubicin 90 mg/mq i.v. every 3 weeks for three cycles

Arm 1

Cyclophosphamide DRUG

Cyclophosphamid 600 mg/mq i.v. every 3 weeks for three cycles

Arm 1

Triptorelin DRUG

Triptorelin 3.75 mg i.m. every 4 weeks until surgery

Arm 1

Exemestane DRUG

Exemestane 25 mg oral continuous daily dose until surgery

Arm 1

Nivolumab DRUG

Nivolumab 240 mg flat dose i.v. every two weeks for 8 cycles

Also known as: BMS-936558

Arm 1

Eligibility Criteria

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

You may qualify if:

• Patients may be included in the study only if they met all the following criteria
• age \>18 yrs
• female patients
• ECOG Performance Status 0-1
• must have signed and dated an IRB/IEC-approved written informed consent form in accordance with regulatory and institutional guidelines before the performance of any protocol-related procedures
• Primary diagnosis of invasive breast cancer, HR positive (ER ≥ 10% and/or PgR ≥10% by IHC) and HER2 negative (IHC 0/1+ and/or FISH/CISH negative) according to local assessment.
• Histologic grade 3 and/or Ki67 \>20% according to local assessment.
• Stage II-IIIA
• Eligible for neoadjuvant chemotherapy according to multidisciplinary evaluation.
• Premenopausal status
• Normal organ and marrow function
• Availability of tumor tissue suitable for biological and molecular examination before starting primary treatment
• Ability to understand and willingness to sign a written informed consent document

You may not qualify if:

• Patients will be excluded from the study for any of the following reasons
• Stage IIIB, IIIC, and inflammatory breast cancer
• Stage IV breast cancer
• Prior treatment with chemotherapy, biologic therapy, endocrine therapy or radiotherapy for the treatment of the newly-diagnosed breast cancer.
• Contraindication to anthracycline-based chemotherapy.
• Received any investigational treatment within 4 weeks of study start.
• Any other concurrent chemotherapy, biologic therapy, endocrine therapy or radiotherapy for cancer treatment.
• Known HIV, HBV, HCV infection or any positive tests for HBV and HCV indicating acute or chronic infection.
• Known severe hypersensitivity to any of the study drugs or excipients or known severe hypersensitivity reactions to monoclonal antibodies.
• Major surgical procedure or significant traumatic injury within 28 days prior to treatment initiation or anticipation of need for major surgery during the course of study treatment.
• History of allogenic organ transplantation
• Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident /stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of treatment initiation.
• Subjects with active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Any other serious or uncontrolled medical disorder, active infection, physical exam finding, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a subject's ability to comply with the study requirements, substantially increase risk to the subject, or impact the interpretability of study results.

Sponsors & Collaborators

• Istituto Oncologico Veneto IRCCS: lead
• University of Padova: collaborator

Study Sites (5)

Arcispedale S. Anna

Cona, FE, Italy

Location

Centro di Riferimento Oncologico di Aviano (CRO)

Aviano, PN, Italy

Location

Azienda Ospedaliera Universitaria di Parma

Parma, PR, 43126, Italy

Location

Arcispedale S. Maria Nuova

Reggio Emilia, RE, Italy

Location

Istituto Oncologico veneto IRCCS

Padua, 35128, Italy

Location

Related Publications (1)

• Dieci MV, Guarneri V, Tosi A, Bisagni G, Musolino A, Spazzapan S, Moretti G, Vernaci GM, Griguolo G, Giarratano T, Urso L, Schiavi F, Pinato C, Magni G, Lo Mele M, De Salvo GL, Rosato A, Conte P. Neoadjuvant Chemotherapy and Immunotherapy in Luminal B-like Breast Cancer: Results of the Phase II GIADA Trial. Clin Cancer Res. 2022 Jan 15;28(2):308-317. doi: 10.1158/1078-0432.CCR-21-2260. Epub 2021 Oct 19.

  PMID: 34667023 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Epirubicin; Cyclophosphamide; Triptorelin Pamoate; exemestane; Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Gonadotropin-Releasing Hormone; 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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• Pierfranco Conte, MD

  University of Padova

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 23, 2018
• First Posted: December 9, 2020
• Study Start: October 5, 2017
• Primary Completion: May 25, 2020
• Study Completion: May 25, 2020
• Last Updated: December 9, 2020

Record last verified: 2020-12

Locations

IT (5)