NEODOXy: Targeting Breast Cancer Stem Cells With Doxycycline

NCT06452394 | Recruiting Phase 2 DMC

• 1 other identifier: SAKK 21/23
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 8

Brief Summary

Despite modern surgical and medical treatments, breast cancer can re-occur and lead 20% of patients to death. During the last 20 years, pre-clinical studies have shown that treatment failures may be due to the presence of a sub-type of cancer cells, the cancer stem cells, which are resistant to chemotherapy and radiotherapy. By chance, doxycycline, an old, inexpensive and safe molecule seems to target effectively these cancer stem cells. This study proposes to check for the clinical efficacy of doxycycline to target the cancer stem cells and improve the response to neoadjuvant chemotherapy in ER+/HER2- breast cancers.

Conditions

Breast Cancer

Keywords

early ER+/HER2- breast cancer; NEODOXy; Doxycycline; Human Epidermal Growth Factor Receptor 2 negative; Estrogen Receptor; Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Difference in the proportion of patients with ALDH1 positive tumors before and after neoadjuvant chemotherapy plus doxycycline.

  Difference in the proportion of patients with Aldehyde Dehydrogenase 1 (ALDH1) positive tumors before and after neoadjuvant chemotherapy plus doxycycline, assessed as follows: Tumor cells expressing ALDH1 will be revealed by immunostaining using an anti-ALDH1 antibody on the pathology slides. In case of residual disease, an ALDH1 positive tumor is defined as having at least 5% of its tumor cells expressing ALDH1. In case of pCR, determined by H\&E staining, ALDH1 will be considered negative.

  From the date of registration to 30 days after last trial treatment

• Pathologic complete response rate after surgery, defined as no invasive residual disease in the breast and in the axillary lymph nodes.

  Pathologic complete response (pCR) rate after surgery in the breast and in the axillary lymph nodes (if biopsy-proven lymph node involvement prior to neoadjuvant treatment), defined as proportion of patients with no residual invasive cancer for each anatomic location (i.e no viable cancer cell on microscopic examination after Hematoxylin and Eosin (H\&E) staining): ypT0-ypTis ypN0.

  From the date of registration to 30 days after last trial treatment

Secondary Outcomes (7)

• Percentage of ALDH1 positive tumor cells

  From the date of registration to 30 days after last trial treatment

• Difference in the percentage of ALDH1 positive tumor cells

  From the date of registration to 30 days after last trial treatment

• Pathological residual disease

  From the date of registration to 30 days after last trial treatment

• Radiological tumor shrinkage

  From the date of registration to 30 days after last trial treatment

• Breast conservation rate

  From the date of registration to 30 days after last trial treatment

Study Arms (1)

NEOadjuvant DOXYcycline

EXPERIMENTAL

neoadjuvant chemotherapy (4 cycles epirubicin 90 mg/m2 + cyclophosphamide 600 mg/m2 q3W followed by 4 cycles weekly paclitaxel (D1, D8, D15) 80 mg/m2) \+ doxycycline (200 mg/day from D5 to D18 of each cycle)

Drug: Doxycyclin

Interventions

Doxycyclin DRUG

Belongs to the class of tetracyclines. It has bacteriostatic activity against a broad range of gram-positive and gram-negative bacteria. Its mechanism of action lies in the binding to the 30S ribosomal subunit

Also known as: Doxyclin

NEOadjuvant DOXYcycline

Eligibility Criteria

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

You may qualify if:

• Written informed consent according to Swiss law and current ICH GCP E6 regulations before registration and prior to any trial specific procedures.
• Histologically confirmed ER+/HER2- primary invasive breast cancer, according to ASCO/CAP Guideline1,2, defined as ER expression rate ≥ 1%.
• Patients are candidate for curative surgery and with a tumor size of at least 2 cm and nodal classification cN0-3 according to the 8th edition, January 2017 of the anatomic TNM classification3.
• Patients with multiple synchronous ipsilateral tumors are allowed, as long as all lesions are ER+/HER2-. Only one target lesion will be considered for ALDH1 primary endpoint, and the target lesion has to be the largest lesion.
• Patients are planned for neoadjuvant chemotherapy according to the local standards.
• Patients accept standard curative surgery after neoadjuvant chemotherapy with 4 cycles of epirubicin and cyclophosphamide (EC) followed by 12 doses of weekly paclitaxel (or nab-paclitaxel).
• Diagnostic tumor tissue is available for the mandatory central pathology examinations; or an additional biopsy is planned in case of lack of remaining material from the diagnostic biopsy, provided that the patient has consented to the optional TR-project.
• Patients with a prior malignancy and treated with curative intention are eligible if all treatment of that malignancy was completed at least 2 years before registration in this trial and the patient has no evidence of disease at registration. Less than 2 years is acceptable for adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
• Male or female patients age ≥ 18 years.
• ECOG performance status 0-1.
• Adequate bone marrow function:
• neutrophil count ≥ 1.5 x 10\^9/L,
• platelet count ≥ 100 x 10\^9/L,
• hemoglobin ≥ 90 g/L.
• Adequate hepatic function:

You may not qualify if:

• Patients with 2 synchronous breast cancers or more of different subtypes (other than ER+/HER2-).
• Metastatic patients.
• Patients having received or planned to undergo neoadjuvant endocrine therapy or other investigational therapies before surgery.
• History of intracranial hypertension (IH).
• Concomitant or recent (within 30 days of registration) treatment with any other experimental drug.
• Concomitant use of drugs contraindicated with doxycycline according to the Swissmedic-approved product information or contraindicated according to the trial protocol.
• Use of dietary supplements, natural therapies, phytotherapy or complementary and integrative medicines (homeopathy, spagyric remedies, etc) without approval of the sponsor.
• Concomitant use of other anti-cancer drugs or radiotherapy.
• Patients having received doxycycline or other antibiotics of the cyclin family within 28 days before registration.
• Known hypersensitivity to cyclin group of substances, including tetracyclines, doxycycline or to any component of the trial drug.
• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (8)

Kantonsspital St.Gallen

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

RECRUITING

Clinique de Genolier

Genolier, Canton of Vaud, 1272, Switzerland

RECRUITING

Kantonsspital Winterthur

Winterthur, Canton of Zurich, 8401, Switzerland

RECRUITING

Kantonsspital Graubünden

Chur, Kanton Graubünden, 7000, Switzerland

RECRUITING

Tumor Zentrum Aarau

Aarau, 5000, Switzerland

RECRUITING

Réseau du sein Lausanne

Lausanne, 1004, Switzerland

RECRUITING

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, CH-1011, Switzerland

RECRUITING

Tumor- und Brustzentrum Ostschweiz

Sankt Gallen, 9016, Switzerland

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Loïc Lelièvre, M.D.

  Centre Hospitalier Universitaire Vaudois (CHUV)

  STUDY CHAIR

Central Study Contacts

Daniela Zoelly, PhD

CONTACT

+41 31 389 91 91; trials@swisscancerinstitute.ch

Study Design

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

Model Details: A prospective, single arm, open label

Study Record Dates

• First Submitted: June 5, 2024
• First Posted: June 11, 2024
• Study Start: July 16, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CH (8)