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Breast CancerPhase 2NCT05601440

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

A Phase 2 study testing RP-6306, Gemcitabine and Observation in people with Breast Cancer, run by Canadian Cancer Trials Group at 10 sites in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Any age
Conditions the study is for
Breast Cancer
What is being tested?
RP-6306, Gemcitabine and Observation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
484 participants
Where
10 sitesCanada
Study dates
13 Jun 2023to 30 Jun 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • Bilirubin ≤ 1.5 x ULN (upper limit of normal)**
  • AST \& ALT ≤ 2.5 x ULN
  • ≤ 5.0 x ULN if patient has liver metastases
  • Serum creatinine ≤ 1.5 x ULN, Creatinine clearance ≥50 mL/min
  • All patients must have received at least 24 weeks of prior CDK4/6i in combination with first line ET for advanced or metastatic disease and have had disease progression on or within 8 weeks of the last dose of CDK4/6i. Patients who have progressed on, or within 12 months of completion of adjuvant therapy with an aromatase inhibitor who are treated with fulvestrant instead of an aromatase inhibitor combined with CDK4/6 inhibitor are only eligible for non fulvestrant containing substudies.
  • In addition, the following systemic therapies may have been given after CDK4/6i / ET prior to screening / enrollment to this study:
  • For enrollment to "second line" substudies:
  • An additional single agent non-fulvestrant/SERD endocrine therapy in the palliative setting is permitted provided patient remains eligible for and can access fulvestrant treatment. Patients who have received prior fulvestrant/SERD are not eligible for fulvestrant containing substudies. Contact CCTG in case of any other prior endocrine therapy other than an aromatase inhibitor or tamoxifen.
  • For enrollment to "third line" substudies:
  • Non-SERD endocrine therapy and targeted agents (for example, PI3K/AKT/PTEN inhibitors unless excluded in substudy-specific eligibility criteria) alone or in combination.
  • Patients who have received a prior targeted agent may not be eligible for substudies that contain the same class of agent. Please refer to substudy-specific eligibility criteria.
  • Note: if a patient has not had fulvrestrant/SERD prior to enrollment to "third line: substudy, single agent fulvestrant/SERD must be given prior to enrollment (unless not possible for reasons such as fulvestrant/SERD not standard of care / not funded in province, patient cannot receive intramuscular injection; contact CCTG for other scenarios).
  • Patients may also have received adjuvant/neoadjuvant systemic therapies; however cytotoxic chemotherapy or antibody drug conjugates (ADC) in the palliative setting are not permissible.
  • Patients receiving LHRH agonists (for example premenopausal patients) may continue on the LHRH agonist, but may not start a LHRH agonist within 12 weeks prior to enrollment.
  • Consult CCTG for other scenarios (for example where short course of other ET is given prior to CDKi + ET, patients who have received investigational drugs, vaccines or immunotherapies) as certain patients may be eligible.
  • All reversible prior toxicity related to prior therapies must have recovered to grade ≤ 1 (consult CCTG in the case of irreversible toxicity) and have adequate washout as follows (screening may occur during the washout period): Longest of the following (for questions or any proposed variance, please discuss with CCTG prior to patient enrollment): Two weeks; 5 half-lives for investigational agents; standard cycle length of standard therapies
  • Patients must not have received a transfusion (platelets or red blood cells) or colony stimulating factors ≤ 4 weeks prior to initiating treatment substudy therapy.
  • Surgery: Prior surgery is permitted provided that a minimum of at least 28 days have elapsed between any major surgical procedure and date of enrollment, and that wound healing has occurred.
  • Radiation: Prior external beam radiation is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose of radiation and date of enrollment. Exceptions may be made for low-dose, non-myelosuppressive radiotherapy after consultation with CCTG. Concurrent radiotherapy is not permitted.
  • Patients must be registered and provide consent prior to blood collection for screening. The screening blood sample cannot be sent for analysis prior to screening registration.
  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to both screening registration as well as enrollment to a specific substudy to document their willingness to participate.
  • Patients must be accessible for treatment and follow up. Patients enrolled on this trial must be treated and followed at the participating centre
  • In accordance with CCTG policy, substudy treatment is to begin within 2 working days of patient enrollment.
  • Women/men of childbearing potential must have agreed to use a highly effective contraceptive method.

Who cannot join

  • 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
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  • 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).
  • Pregnant or breastfeeding women (including within 1 month following last dose of protocol therapy).
  • Patients with history of central nervous system metastases or spinal cord compression unless they have received definitive treatment such as resection or radiation, are clinically stable and do not require corticosteroids; corticosteroids must have been discontinued at least 7 days prior to enrollment.
  • Patients who are unable to swallow oral medication and/or have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. Crohn's disease, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, active bowel inflammation (e.g. diverticulitis) or small bowel resection), unless agreed with CCTG (exceptions may be given if a parenteral treatment substudy is available/appropriate).
  • Patients with a history of non-compliance to medical regimens.
  • See Section 7.3 and individual treatment substudies for a list of concomitant medications that are not permitted.
  • Many substudies include drugs that have a risk for thrombocytopenia; therefore, participants should be advised to use caution when taking oral anticoagulants (e.g. warfarin) and antiplatelet drugs (e.g. aspirin). Patients with history of deep vein thrombosis or pulmonary embolus who are being treated with therapeutic doses of low molecular weight heparin, direct factor Xa inhibitors or prophylactic dose anticoagulants may be enrolled, but the use of warfarin should be avoided.

Trial locations and contacts

10 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Lesley Seymour contact

613-533-6430

lseymour@ctg.queensu.ca

Laura Pearce contact

613-533-6430

lpearce@ctg.queensu.ca

10 sites in 1 country

Canada10 sites, 9 recruiting

  • Arthur J.E. Child Comprehensive Cancer Centre

    Calgary, Alberta, T2N 5G2

    Patricia Tang, 403 521-3490

    Recruiting

  • QEII Health Sciences Centre

    Halifax, Nova Scotia, B3H 1V7

    Daniel Rayson, 902 473-6106

    Recruiting

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

    Nidhi Kumar Tyagi, 905 387-9495

    Recruiting

  • BCCA - Kelowna

    Kelowna, British Columbia, V1Y 5L3

    Sara Kristina Taylor, 250 712-3996

    Recruiting

  • Kingston Health Sciences Centre

    Kingston, Ontario, K7L 2V7

    Brooke Wilson

    Recruiting

  • The Jewish General Hospital

    Montreal, Quebec, H3T 1E2

    Parvaneh Fallah, 614 340-8222

    Recruiting

  • Ottawa Hospital Research Institute

    Ottawa, Ontario, K1H 8L6

    Moira Rushton

    Recruiting

  • Odette Cancer Centre

    Toronto, Ontario, M4N 3M5

    Suspended

  • University Health Network

    Toronto, Ontario, M5G 2M9

    David Cescon, 416 946-2245

    Recruiting

  • BCCA - Vancouver

    Vancouver, British Columbia, V5Z 4E6

    Nathalie Levasseur, 604 877-6000

    Recruiting

Other trials in Canada

About this study

Official title: A Liquid-biopsy Informed Platform Trial to Evaluate Treatment in CDK4/6-inhibitor Resistant ER+/HER2- Metastatic Breast Cancer

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

Read the detailed description

This is a 2-stage master protocol with multiple substudies testing investigational drugs/drug combinations in patients with CDK4/6-inhibitor resistant ER+/HER2- metastatic breast cancer. First line endocrine therapy (1LET, aromatase inhibitors; AI) improve clinical outcomes, but are not curative, and acquired resistance develops (median ~2 years). CDK4/6i-resistant MBC is a clinical unmet need, and is marked by numerous potential resistance alterations / mechanisms. Currently, most patients receive second line (2L) ET (e.g., fulvestrant) which has a median progression-free survival (PFS) of ~2 months in this setting. Circulating tumour DNA (ctDNA) is detectable in peripheral blood in >90% of patients with MBC.

Patients who wish to participate but progression has not yet occurred may be enrolled in the monitoring substudy and followed until progression. This monitoring component of IND.241 aims to characterize the molecular and clinical features of CDK4/6i resistance as it occurs after first line CDK4/6i + AI. Besides addressing the principal objectives described above (ctDNA genotyping and evaluation of dynamic changes in ctDNA levels), banked samples will create a biorepository for interrogation of emerging assays (e.g., DNA methylation, or single cell analyses) that may have prognostic or predictive application. These data will inform future efforts that may consider intervention prior to clinical treatment failure.

Conditions
Breast Cancer
Being tested
RP-6306, Gemcitabine, Observation, Niraparib, Fulvestrant
Medical subject headings
Breast Neoplasms

What participants receive

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

  • RP-6306Drug

    Also called Lunresertib

    Dose and schedule will be assigned at enrolment

  • GemcitabineDrug

    Dose and schedule will be assigned at enrolment

  • ObservationOther

    Monitoring arm

  • NiraparibDrug

    Dose and schedule will be assigned at enrolment

  • FulvestrantDrug

    Dose and schedule will be assigned at enrolment

  • RP-3500Drug

    Also called Camonsertib

    Dose and schedule will be assigned at enrolment

  • CFI-402257Drug

    Dose and schedule will be assigned at enrolment

  • CFI-400945Drug

    Dose and schedule will be assigned at enrolment

  • Sacituzumab govitecanDrug

    Dose and schedule will be assigned at enrolment

Study groups in NCT05601440
Study groupRoleWhat they receive
Substudy A - MonitoringExperimentalNot described
Receives: Other: Observation
Substudy B - RP-6306 + Gemcitabine - Arm Permanently ClosedExperimentalNot described
Receives: Drug: RP-6306; Drug: Gemcitabine
Substudy C - Niraparib + FulvestrantExperimentalNot described
Receives: Drug: Niraparib; Drug: Fulvestrant
Substudy D - RP-6306 + RP-3500 - Arm Permanently ClosedExperimentalNot described
Receives: Drug: RP-6306; Drug: RP-3500
Substudy E - CFI-402257ExperimentalNot described
Receives: Drug: CFI-402257
Substudy F - CFI-400945ExperimentalNot described
Receives: Drug: CFI-400945
Substudy G - Sacituzumab GovitecanExperimentalNot described
Receives: Drug: Sacituzumab govitecan

What is being measured

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

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

    Measured: 5 years

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

    Measured: 5 years

Secondary outcomes (3)

  1. Number and severity of adverse events

    Measured: 5 years

  2. Progression-free survival (PFS)

    Measured: 5 years

  3. Overall survival

    Measured: 5 years

Timeline

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

  1. First posted1 Nov 2022
  2. Study start13 Jun 2023
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion30 Jun 2028 (estimated)

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
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
484 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05601440
Sponsor's protocol ID
I241
Status last verified
May 2026
First submitted
25 Oct 2022
Last updated
7 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RP-6306, Gemcitabine and Observation in people with Breast Cancer, run by Canadian Cancer Trials Group at 10 sites in Canada.

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 39 inclusion and 21 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: looking for participants now, as of the sponsor's last update on 7 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Canada. 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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Lesley Seymour (613-533-6430, lseymour@ctg.queensu.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate whether biomarker selection improves outcomes as assessed by RECIST 1.1 for overall response rate (time frame: 5 years). The study lists 2 primary outcomes in all. 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 NCT05601440.

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 7 May 2026.

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