Study of combination of metronomic chemotherapy and reactivator of immune response in inflammatory breast cancer spread to the chest wall.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Istituto Europeo Di Oncologia S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 May 2020 → 3 Dec 2025

Decision date (initial)

2024-07-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-507365-26-00

EudraCT number

2017-003343-37

ClinicalTrials.gov

NCT03971045

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Assessment of the efficacy of pembrolizumab and Metronomic Cyclophosphamide according to Immune-related RECIST (irRECIST) criteria in patients with chest wall breast cancer.

Secondary objectives 1

1. Duration of response (DoR); Time to progression (TTP); Progression-free survival (PFS); Overall survival (OS)

Conditions and MedDRA coding

Locally recurrent, inoperable, and/or metastatic inflammatory breast cancer with lymphangitic spread to the chest wall

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Histologically proven, PDL1 (=1%) positive and/or tumor infiltrating lymphocyte positive (=1%) locally advanced “chest wall” breast cancer (with or without distant metastases), who have been treated with chemotherapy or radiation therapy may be eligible for this study. Patients with cutaneous metastases only (with or without evidence
2. Patients must have tissue accessible for serial biopsies.
3. Expected survival of > 3 months.
4. Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
5. Be 18 years of age on day of signing informed consent
6. Be a female or male subject with IBC with lymphangitic spread to the chest wall. ER, PgR and HER2 status determination is required for enrollment.
7. Have provided tissue for PD-L1 biomarker analysis from a newly obtained core or excisional biopsy of a tumor lesion (mandatory) and received permission for enrollment from the Core Lab based on the adequacy of the biopsy specimen. Repeat samples may be required if adequate tissue is not provided.
8. Have measurable metastatic disease based on irRECIST criteria as determined by central radiology review. Tumor lesions situated in a previously irradiated area are considered measurable, if progression has been demonstrated in such lesions.
9. Note: The exact same image acquisition and processing parameters should be used throughout the study.
10. Have a performance status of 0 or 1 on the ECOG Performance Scale. Assessment should be performed within 10 days of treatment initiation.
11. Female subjects of childbearing potential (Section 2.9.2) must be willing to use an adequate method of contraception as outlined in Section 2.9.2 – Contraception, for the course of the study through 120 days after the last dose of study medication.
12. Male subjects childbearing potential (Section 2.9.2) must agree to use an adequate method of contraception as outlined in Section 2.9.2- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy..
13. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
14. Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
15. Patients with hormone receptor-positive and/or HER2-positive breast cancer would be eligible for the study only if their disease is considered refractory to hormonal or anti-HER2 agents, respectively, and no further hormonal or anti-HER2 treatment is indicated.
16. Demonstrate adequate organ function in all screening labs that should be performed within 10 days of treatment initiation.

Exclusion criteria 15

1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
3. Has a known history of active TB (Bacillus Tuberculosis)
4. Hypersensitivity to pembrolizumab or any of its excipients.
5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and may qualify for the study. - Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
8. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
9. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
10. Has known history of, or any evidence of active, non-infectious pneumonitis.
11. Has an active infection requiring systemic therapy.
12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
14. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint will be objective response (confirmed CR or PR as best overall response) based on irRECIST criteria and also based on evaluable disease.

Secondary endpoints 3

1. Progression free survival
2. Duration of response
3. Overall survival

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Europeo Di Oncologia S.r.l.

Sponsor organisation

Istituto Europeo Di Oncologia S.r.l.

Address

Via Giuseppe Ripamonti 435

City

Milan

Postcode

20141

Country

Italy

Scientific contact point

Organisation

European Institute Of Oncology S.r.l.

Contact name

Giuseppe Curigliano

Public contact point

Organisation

European Institute Of Oncology S.r.l.

Contact name

Giuseppe Curigliano

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications