Liquid-biopsy Informed Platform Trial to Evaluate CDK4/6-inhibitor Resistant ER+/HER2- Metastatic Breast Cancer

NCT05601440 | Recruiting Phase 2 DMC

• 1 other identifier: I241
• Study Type: interventional
• Target: 484
• Locations: 1 country
• Sites: 10

Brief Summary

This study is being done to answer the following question: Can testing breast cancer for DNA abnormalities or "biomarkers" help predict which patients are most likely to be helped by certain treatments? The pre-study screening is being done to test a sample of blood (or tumour tissue) for biomarkers to see if patients can participate in the study

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Evaluate whether biomarker selection improves outcomes as assessed by RECIST 1.1 for overall response rate

  5 years

• Evaluate whether biomarker selection improves outcomes as assessed by RECIST 1.1 for clinical benefit rate

  5 years

Secondary Outcomes (3)

• Number and severity of adverse events

  5 years

• Progression-free survival (PFS)

  5 years

• Overall survival

  5 years

Study Arms (7)

Substudy A - Monitoring

EXPERIMENTAL

Other: Observation

Substudy B - RP-6306 + Gemcitabine - Arm Permanently Closed

EXPERIMENTAL

Drug: RP-6306; Drug: Gemcitabine

Substudy C - Niraparib + Fulvestrant

EXPERIMENTAL

Drug: Niraparib; Drug: Fulvestrant

Substudy D - RP-6306 + RP-3500 - Arm Permanently Closed

EXPERIMENTAL

Drug: RP-6306; Drug: RP-3500

Substudy E - CFI-402257

EXPERIMENTAL

Drug: CFI-402257

Substudy F - CFI-400945

EXPERIMENTAL

Drug: CFI-400945

Substudy G - Sacituzumab Govitecan

EXPERIMENTAL

Drug: Sacituzumab govitecan

Interventions

RP-6306 DRUG

Dose and schedule will be assigned at enrolment

Also known as: Lunresertib

Substudy B - RP-6306 + Gemcitabine - Arm Permanently Closed; Substudy D - RP-6306 + RP-3500 - Arm Permanently Closed

Gemcitabine DRUG

Dose and schedule will be assigned at enrolment

Substudy B - RP-6306 + Gemcitabine - Arm Permanently Closed

Observation OTHER

Monitoring arm

Substudy A - Monitoring

Niraparib DRUG

Dose and schedule will be assigned at enrolment

Substudy C - Niraparib + Fulvestrant

Fulvestrant DRUG

Dose and schedule will be assigned at enrolment

Substudy C - Niraparib + Fulvestrant

RP-3500 DRUG

Dose and schedule will be assigned at enrolment

Also known as: Camonsertib

Substudy D - RP-6306 + RP-3500 - Arm Permanently Closed

CFI-402257 DRUG

Dose and schedule will be assigned at enrolment

Substudy E - CFI-402257

CFI-400945 DRUG

Dose and schedule will be assigned at enrolment

Substudy F - CFI-400945

Sacituzumab govitecan DRUG

Dose and schedule will be assigned at enrolment

Substudy G - Sacituzumab Govitecan

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically and/or cytologically confirmed, advanced / metastatic breast cancer, ER \>10% and not HER2 overexpressing/amplified as per ASCO/CAP criteria. Patients with locally advanced or inflammatory disease without distant metastases that is potentially resectable or treatable with curative intent are not eligible
• All patients must have a formalin fixed paraffin embedded tissue block (from primary or metastatic tumour) available and must have provided informed consent for the release of the block
• Patients must have had objective disease progression demonstrated on (defined as while taking or within 8 weeks of the last dose) first line CDK4/6i + ET for MBC. Patients who discontinued CDK4/6i + ET without disease progression more than 8 weeks prior to objective disease progression (toxicity, patient request) are not eligible. Patients must have received at least 24 weeks of first line CDK4/6i + ET therapy
• Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 21 days prior to enrollment (within 28 days if negative). All patients must have measurable disease as defined by RECIST 1.1.
• The criteria for defining measurable disease are as follows:
• Chest x-ray ≥ 20 mm
• CT scan (with slice thickness of 5 mm) ≥ 10 mm: longest diameter
• Physical exam (using calipers) ≥ 10 mm
• Lymph nodes by CT scan ≥ 15 mm: measured in short axis
• Patients must be ≥ 18 years of age
• Patients must have an ECOG performance status 0 or 1
• Patients must have a life expectancy ≥ 3 months.
• Hemoglobin ≥90 g/L\*
• Absolute neutrophils ≥ 1.5 x 10\^9/L (1500/µL)
• Platelets ≥ 100 x 109/L (100 x 10\^3/µL)

You may not qualify if:

• Patients with a history of other malignancies, including Myelodysplastic syndrome (MDS) or Acute myeloid leukemia (AML) except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other malignancies curatively treated with no evidence of disease for ˃ 2 years and which do not require ongoing treatment.
• Patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to protocol.
• Infection includes but is not limited to active infection requiring systemic therapy and active or known human immunodeficiency virus (HIV) with detectable viral load, known hepatitis B surface antigen or positive hepatitis C antibody
• Pneumonitis or any history of pneumonitis requiring steroids (any dose)
• Participant has received a live attenuated vaccine within 30 days of planned start of study therapy. Note: Seasonal vaccines for influenze are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and not allowed.
• Known primary immunodeficiency
• Patients with recent clinically significant cardiac disease, including:
• Angina pectoris, symptomatic pericarditis, coronary artery bypass grafting, coronary angioplasty, or stenting, or myocardial infarction in the previous 12 months;
• History of documented congestive heart failure (New York Heart Association functional classification III-IV) or cardiomyopathy
• Uncontrolled hypertension (per Canadian guidelines)
• All patients should have a LVEF ≥ 50%.
• Patients with HER2 positive breast cancer (based on the most recent assessment, according to ASCO/CAP criteria).
• History of hypersensitivity to any of the study drugs or their components.
• Patients may not receive concurrent treatment with other anti-cancer therapy (other than bone-targeted therapy, if already taking and stable) or investigational agents while on protocol therapy.
• Patients with prior allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead

Study Sites (10)

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

RECRUITING

BCCA - Kelowna

Kelowna, British Columbia, V1Y 5L3, Canada

RECRUITING

BCCA - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

RECRUITING

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

RECRUITING

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

RECRUITING

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

SUSPENDED

University Health Network

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

The Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Gemcitabine; Observation; niraparib; Fulvestrant; CFI-402257; 2-(3-(4-((2,6-dimethylmorpholino)methyl)styryl)-1H-indazol-6-yl)-5'-methoxyspiro(cyclopropane-1,3'-indolin)-2'-one; sacituzumab govitecan

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Methods; Investigative Techniques; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• David Cescon

  University Health Network, Princess Margaret Hospital, Toronto ON Canada

  STUDY CHAIR

• John Hilton

  Ottawa Hospital Research Institute

  STUDY CHAIR

• Nathalie Levasseur

  BCCA - Vancouver Cancer Centre

  STUDY CHAIR

• Stephen Chia

  BCCA - Vancouver Cancer Centre

  STUDY CHAIR

• Moira Rushton

  Ottawa Hospital Research Institute

  STUDY CHAIR

Central Study Contacts

Lesley Seymour

CONTACT

613-533-6430; lseymour@ctg.queensu.ca

Laura Pearce

CONTACT

613-533-6430; lpearce@ctg.queensu.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2022
• First Posted: November 1, 2022
• Study Start: June 13, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (10)