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Breast CancerEarly Phase 1ONAWANCT04142892

Onapristone as Preoperative Treatment for Postmenopausal Women With Hormone Receptor + and HER2- Breast Cancer

A Early Phase 1 study testing Onapristone in people with Breast Cancer, run by SOLTI Breast Cancer Research Group at 4 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

ONAWA is a window of opportunity, prospective, multicenter, phase 0 trial which evaluates the effect of onapristone (ONA) on proliferation after 3 weeks of treatment in postmenopausal women with ER+/PgR+ and HER2-negative early breast cancer amenable to pre-operative endocrine therapy and surgery. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Onapristone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
4 sitesSpain
Study dates
6 Nov 2020to 30 Apr 2021
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written and signed informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.
  • Age ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Postmenopausal women defined either by:
  • Age ≥60 or
  • Age < 60 and amenorrhea for ≥ 12 months and FSH and E2 plasmatic levels in the post-menopausal range per local standards or
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  • Prior bilateral oophorectomy (28 days before Day 1 of the study treatment).
  • Histologically confirmed invasive breast carcinoma eligible for surgery with all the following characteristics:
  • Primary tumor diameter of at least 15 mm (cT1c-3) as measured by ultrasound (US).
  • No regional lymph node metastases by imaging or clinical examination (cN0).
  • ER-positive and PgR-positivity (ER+/PgR+), as assessed locally, defined by American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) clinical practice guidelines.
  • HER2-negative status, as assessed locally, defined by American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP)
  • In case of multifocal tumors (defined as the presence of two or more foci of cancer within the same breast quadrant), the largest lesion must be measured in at least one dimension of minimal 15 mm per US. This lesion will be designated as 'target' lesion for all subsequent evaluations. ER+/PgR+ and HER2-negative status must be documented in all the tumor foci. Site markers should be placed in each accessible lesion, even if mastectomy is planned, to facilitate correct tumor assessment by the pathologist.
  • Cells staining positive for Ki67 ≥ 15% as locally assessed.
  • Available pre-treatment formalin-fixed paraffin-embedded (FFPE) tumor specimen or possibility to obtain one. Minimal sample requirements are: at least 2 tumor cylinders with a minimal tissue surface of 10 mm2, containing ≥10% tumor cells, enough to obtain at least 2 cuts of 10 µm each. Tumor cylinder will be mandatory.
  • No clinical or radiographic evidence of distant metastases (M0).
  • Adequate hematologic and organ function within 14 days before the first study treatment on Day 1, defined by the following:
  • Neutrophils (ANC ≥1500/μL).
  • Hemoglobin ≥9 g/dL (with no need for transfusions).
  • Platelet count ≥100000/μL.
  • Serum albumin ≥3 g/dL.
  • Calculated creatinine clearance of ≥ 60 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation:
  • (140 - age) x (weight in kg) x 0.85 72 x (serum creatinine in mg/dL).
  • International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN and activated partial thromboplastin time (aPTT) within therapeutic range.
  • Potassium, total Calcium (corrected for serum albumin), Magnesium and Natrium with institutional normal limits or corrected with normal limits with supplement before first dose of study medication.
  • Ability to swallow study drug and comply with study requirements.
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Who cannot join

  • Inoperable locally advanced or inflammatory (i.e., Stage III) breast cancer.
  • Metastatic (Stage IV) breast cancer.
  • Invasive bilateral o multicentric breast cancer.
  • Patients requiring neoadjuvant chemotherapy or immediate surgical intervention.
  • Patients who have undergone sentinel lymph node biopsy or tumor excisional biopsy prior to study treatment.
  • Prior malignancy within 3 years prior to randomization, except curatively treated non-melanoma skin cancer, in situ cervical cancer or adequately treated Stage I or II cancer from which the patient is currently in complete remission or other cancer from which the patient has been disease-free for 2 years.
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  • Congenital long QT syndrome or screening QT interval corrected using Fridericia's formula (QTcF) > 480 milliseconds or any clinically significant cardiac rhythm abnormalities.
  • Liver function tests documented within the screening period and on Day 1 of treatment period:
  • Total bilirubin >1.5x the upper limit of normal (ULN) unless the patient has documented non-malignant disease (e.g. Gilbert´s syndrome) for whom conjugated bilirubin must be under ULN.
  • AST and ALT >2.5x ULN. f. Alkaline phosphatase ALP >2x ULN.
  • Concurrent, serious, uncontrolled infections or current known infection with HIV (testing is not mandatory).
  • Known hypersensitivity to any of the study drugs, including excipients.
  • History or clinical evidence of any liver or biliary pathology including cirrhosis, infectious disease, inflammatory conditions, steatosis, or cholangitis (including ascending cholangitis, primary sclerosing cholangitis, obstruction, perforation, fistula of biliary tract, spasm of sphincter of Oddi, biliary cyst or biliary atresia).
  • Known clinically significant history active viral or other hepatitis (e.g., positive for hepatitis B surface antigen [HBsAg] or hepatitis C virus [HCV] antibody at screening), current drug or alcohol abuse, or cirrhosis.
  • Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [HBcAg] antibody test) are eligible.
  • Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Chronic adrenal failure or is receiving concurrent long-term corticosteroid therapy. The following corticosteroid uses are permitted: single doses, topical applications (e.g. for rash), inhaled sprays (e.g. for obstructive airway diseases), eye drops or local injections (e.g. intra-articular).
  • Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to swallow pills.
  • History of or clinical evidence of significant co-morbidities that, in the judgment of the investigator, may interfere with the conduction of the study, the evaluation of response, or with informed consent.
  • Received an investigational product or been treated with an investigational device within 30 days prior to first drug administration or plans to start any other investigational product or device study within 30 days after last drug administration.
  • Hormonal treatments for other indications such as osteoporosis, breast cancer prevention, hormonal substitutive therapy, such as raloxifene, tamoxifen, estrogen, progestins. If a patient is on natural products known to contain progestins, they must be stopped 14 days prior to beginning study treatment.
  • Used any prescription medication during the prior 1 month that the investigator judges is likely to interfere with the study or to pose an additional risk to the patient in participating, specifically inhibitors or inducers of cytochrome P450 (CYP)3A4.
  • Major surgical procedure or significant traumatic injury within 30 days prior to enrollment.
  • Assessment by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Trial locations and contacts

4 sites in 1 country.

Spain4 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clínic de Barcelona

    Barcelona

  • Hospital Universitari Arnau de Vilanova de Lleida

    Lleida, 25198

  • Hospital Universitario Sant Joan de Reus

    Tarragona

Other trials in Spain

About this study

Official title: A Window of Opportunity Trial of Onapristone as Preoperative Treatment for Postmenopausal Women With Hormone Receptor-Positive and HER2-negative Breast Cancer

ONAWA is a window of opportunity, prospective, multicenter, phase 0 trial which evaluates the effect of onapristone (ONA) on proliferation after 3 weeks of treatment in postmenopausal women with ER+/PgR+ and HER2-negative early breast cancer amenable to pre-operative endocrine therapy and surgery.

Read the detailed description

The main hypothesis is that onapristone, an antiprogestin will induce a significant proliferative arrest in HR+/HER2-negative breast cancer. The primary endpoint is chosen based on reports which related the 2.7% Ki67 value (natural log of 1) both after a 15 days1 or 3-4 months of neoadjuvant endocrine treatment with favorable breast cancer relapse free and overall survival2,3. Hence, this Ki67 cut-off (Complete Cell Cycle Arrest, or CCCA) has been consistently used in recent trials as an acceptable surrogate marker of clinical and biological efficacy, even though the achievement of a pathological complete response is very unusual in luminal tumors after preoperative endocrine therapy. Trials with biological endpoint, including the so-called window of opportunity trials such as the ONAWA study provide tumor tissue before and after a short course of a given therapy for biomarker analyses of response and resistance. The aim of these studies is to improve the investigator's understanding regarding the biologic effect of a given drug, in order to better define its target population early in its development without interfering with the standard treatment pattern of the patient.

Conditions
Breast Cancer
Being tested
Onapristone
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OnapristoneDrug

    50 mg given orally (PO), twice a day (BID), in a continuous schedule (QD) during 3 weeks (+/-3 days)

Study groups in NCT04142892
Study groupRoleWhat they receive
OnapristoneExperimental50 mg given orally (PO), twice a day (BID), in a continuous schedule (QD). 3 weeks of (+/-3 days) of ONA treatment
Receives: Drug: Onapristone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete Cell Cycle Arrest (CCCA)

    CCCA rate determined by Ki67 < 2.7%

    Measured: after 3 weeks of ONA therapy

Secondary outcomes (8)

  1. IHC of tumor expression

    IHC of tumor expression of ER, PgR, CD24, CD44, ALDH1, Ser294-PgR, Ki67

    Measured: after 3 weeks of ONA therapy

  2. PAM50 (Prediction Analysis of Microarray 50) subtype change

    PAM50 subtype changes upon ONA therapy

    Measured: after 3 weeks of ONA therapy

  3. antiproliferative effect

    Suppression of PAM50 11-gene proliferation signature according to PAM50 subtypes upon treatment.. These changes will be analyzed according to the formula: Mean suppression = 100 - [geometric mean (post-treatment / pretreatment · 100)].

    Measured: after 3 weeks of ONA therapy

  4. proliferation score

    mean suppression of PAM50 11-gene proliferation signature according to PAM50 subtypes

    Measured: after 3 weeks of ONA therapy

  5. gene expression changes

    • expression of 770 genes across of 23 categories of BC tumor biology
    • changes in the expression of the 16-PgR target genes

    Measured: after 3 weeks of ONA therapy

  6. molecular markers in blood

    Estradiol and progesterone levels

    Measured: after 3 weeks of ONA therapy

  7. identification putative prognostic and predictive biomarkers

    • Development of a gene signature of response to ONA based on changes in the expression of 770 genes by the nCounter Breast 360TM panel in the tumor.
    • Analysis of the presence of ctDNA and its dynamics after ONA treatment.

    Measured: after 3 weeks of ONA therapy

  8. Adverse Events (AEs)

    Incidence, duration and severity of Adverse Events (AEs) assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 5.0, including treatment discontinuations.

    Measured: after 3 weeks of ONA therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2019
  2. Study start6 Nov 2020
  3. Primary completion30 Apr 2021
  4. Study completion30 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
window of opportunity, prospective, multicenter, phase 0 trial
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04142892
Sponsor's protocol ID
ONAWA (SOLTI-1802)
Other IDs
2019-001433-13, 2019
Acronym
ONAWA
Status last verified
Mar 2022
First submitted
24 Oct 2019
Last updated
1 Apr 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bellet M, Ferrero-Cafiero JM, Bergamino Sirven M, Falato C, Gonzalez X, Amillano K, Chic N, Morales S, Gasol A, Nuciforo P, Villacampa G, Villagrasa P, Diep CH, Seelig D, Lange C, D'Assoro A, Prat A, Pascual T, Saura C. Preoperative onapristone-XR in postmenopausal women with progesterone receptor-positive (PgR+)/HER2-negative early breast cancer: SOLTI-1802 ONAWA trial results. NPJ Breast Cancer. 2026 May 29. doi: 10.1038/s41523-025-00887-9. Online ahead of print.

    PubMed 42215464

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Onapristone in people with Breast Cancer, run by SOLTI Breast Cancer Research Group at 4 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Cell Cycle Arrest (CCCA) (time frame: after 3 weeks of ONA therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04142892, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2022.

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