NEODOXy: Targeting Breast Cancer Stem Cells With Doxycycline
ConditionBreast Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorSwiss Cancer Institute
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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).
Trial design
Design model
Single group
Treatments tested in this trial
Doxycyclin
DrugBelongs 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
Treatment groups
50 Participants
are divided into 1 treatment groupGroup A: NEOadjuvant DOXYcyclineExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
From the date of registration to 30 days after last trial treatment2
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.
Time frame
From the date of registration to 30 days after last trial treatmentSecondary outcomes
1
Percentage of ALDH1 positive tumor cells
Difference in the percentage of ALDH1 positive tumor cells before and after neoadjuvant chemotherapy plus doxycycline
Time frame
From the date of registration to 30 days after last trial treatment2
Difference in the percentage of ALDH1 positive tumor cells
Category of the difference in the percentage of ALDH1 positive tumor cells before and after neoadjuvant chemotherapy plus doxycycline
Time frame
From the date of registration to 30 days after last trial treatment3
Pathological residual disease
Pathological residual disease using the validated residual cancer burden score (RCB score)
Time frame
From the date of registration to 30 days after last trial treatment4
Radiological tumor shrinkage
Radiological tumor shrinkage at mid-term and at completion of neoadjuvant treatment
Time frame
From the date of registration to 30 days after last trial treatmentSponsors and contacts
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Source ClinicalTrials.gov