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

NCT04142892 | Completed Early Phase 1

• 2 other identifiers: ONAWA (SOLTI-1802)2019-001433-13
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Complete Cell Cycle Arrest (CCCA)

  CCCA rate determined by Ki67 \< 2.7%

  after 3 weeks of ONA therapy

Secondary Outcomes (8)

• IHC of tumor expression

  after 3 weeks of ONA therapy

• PAM50 (Prediction Analysis of Microarray 50) subtype change

  after 3 weeks of ONA therapy

• antiproliferative effect

  after 3 weeks of ONA therapy

• proliferation score

  after 3 weeks of ONA therapy

• gene expression changes

  after 3 weeks of ONA therapy

Study Arms (1)

Onapristone

EXPERIMENTAL

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

Drug: Onapristone

Interventions

Onapristone DRUG

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

Onapristone

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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:
• d. 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.
• e. 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.

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead

Study Sites (4)

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, 25198, Spain

Location

Hospital Universitario Sant Joan de Reus

Tarragona, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

onapristone

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: window of opportunity, prospective, multicenter, phase 0 trial

Study Record Dates

• First Submitted: October 24, 2019
• First Posted: October 29, 2019
• Study Start: November 6, 2020
• Primary Completion: April 30, 2021
• Study Completion: April 30, 2021
• Last Updated: April 1, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4)