484 Participants Needed

Liquid Biopsy-Informed Therapy for Breast Cancer

Recruiting at 11 trial locations
LS
LP
Overseen ByLaura Pearce
Age: Any Age
Sex: Any
Trial Phase: Phase 2
Sponsor: Canadian Cancer Trials Group
Must be taking: CDK4/6 inhibitors, Endocrine therapy
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial protocol does not clearly specify if you must stop taking your current medications. However, it mentions that certain medications are not permitted during the study, and there is a washout period (time without taking certain medications) required for some prior therapies. It's best to discuss your specific medications with the trial coordinators.

Is the treatment generally safe for humans?

Niraparib has been studied for safety in various cancers, including breast and prostate cancer, and is generally considered safe, with known side effects that are manageable.12345

What makes the drug combination of Fulvestrant, Gemcitabine, Niraparib, and RP-6306 unique for breast cancer treatment?

This drug combination is unique because it uses a liquid biopsy to inform therapy, potentially allowing for more personalized treatment. Additionally, it combines Fulvestrant, a hormone therapy, with Niraparib, a PARP inhibitor, and other agents, which may offer a novel approach compared to standard treatments that typically do not use this combination.12678

Research Team

DC

David Cescon

Principal Investigator

University Health Network, Princess Margaret Hospital, Toronto ON Canada

NL

Nathalie Levasseur

Principal Investigator

BCCA - Vancouver Cancer Centre

SC

Stephen Chia

Principal Investigator

BCCA - Vancouver Cancer Centre

JH

John Hilton

Principal Investigator

Ottawa Hospital Research Institute

MR

Moira Rushton

Principal Investigator

Ottawa Hospital Research Institute

Eligibility Criteria

This trial is for adults with ER+/HER2- metastatic breast cancer that has worsened after CDK4/6 inhibitor therapy. Participants must have a life expectancy of at least 3 months, be able to receive treatment and follow-up at the center, and not have had certain treatments or conditions that could interfere with the study.

Inclusion Criteria

My side effects from previous treatments have mostly gone away.
It's been over 28 days since my last major surgery and my wounds have healed.
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.
See 25 more

Exclusion Criteria

You have a known condition that weakens your immune system.
I do not have any serious infections or illnesses that would interfere with the treatment.
I have not received a live vaccine within the last 30 days, except for non-live COVID-19 vaccines.
See 18 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive investigational drugs/drug combinations based on biomarker testing

8-12 weeks

Monitoring

Participants are monitored for progression and molecular changes in CDK4/6i resistance

Until progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • CFI-400945
  • CFI-402257
  • Fulvestrant
  • Gemcitabine
  • Niraparib
  • Observation
  • RP-6306
Trial Overview The trial tests if liquid biopsies can predict which patients will benefit from specific treatments like RP-6306, Gemcitabine, Niraparib, Fulvestrant or just observation. It involves screening blood/tissue for biomarkers before starting any substudy treatment.
Participant Groups
4Treatment groups
Experimental Treatment
Group I: Substudy D - RP-6306 + RP-3500Experimental Treatment2 Interventions
Group II: Substudy C - Niraparib + FulvestrantExperimental Treatment2 Interventions
Group III: Substudy B - RP-6306 + GemcitabineExperimental Treatment2 Interventions
RP-6306 80mg BID D1-3, D8-10 and D15-17. Gemcitibine D1 and D8
Group IV: Substudy A - MonitoringExperimental Treatment1 Intervention
Monitoring substudy. Biomarker+ (6=23); Biomarker- (n=6-23).

Fulvestrant is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺
Approved in European Union as Faslodex for:
  • Hormone receptor-positive metastatic breast cancer
  • Locally advanced breast cancer
🇺🇸
Approved in United States as Faslodex for:
  • Hormone receptor-positive metastatic breast cancer
  • Locally advanced breast cancer
🇨🇦
Approved in Canada as Faslodex for:
  • Hormone receptor-positive metastatic breast cancer
  • Locally advanced breast cancer
🇯🇵
Approved in Japan as Faslodex for:
  • Hormone receptor-positive metastatic breast cancer
  • Locally advanced breast cancer

Find a Clinic Near You

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials
135
Recruited
70,300+

Findings from Research

Niraparib at a dose of 200 mg/day was determined to be the recommended phase 2 dose when combined with abiraterone acetate plus prednisone (AAP) for patients with metastatic castration-resistant prostate cancer (mCRPC), as it showed a tolerable safety profile with no new safety signals.
The combination of niraparib with apalutamide resulted in a higher incidence of dose-limiting toxicities, leading to the decision not to further evaluate this combination, highlighting the importance of monitoring drug interactions in treatment regimens.
Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE).Saad, F., Chi, KN., Shore, ND., et al.[2021]
In the BELLE-2 phase III study, buparlisib combined with fulvestrant showed a trend towards improved overall survival (OS) compared to placebo plus fulvestrant in patients with advanced hormone receptor-positive breast cancer, although the results were not statistically significant.
Patients receiving buparlisib experienced significantly higher rates of grade III/IV adverse events, such as elevated liver enzymes and hyperglycemia, suggesting that while the treatment may offer some benefits, it also comes with notable safety concerns.
Buparlisib plus fulvestrant versus placebo plus fulvestrant for postmenopausal, hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer: Overall survival results from BELLE-2.Campone, M., Im, SA., Iwata, H., et al.[2019]
Niraparib, administered at doses of 200 mg and 300 mg daily, was found to be tolerable in Japanese patients with advanced solid tumors, with only one case of dose-limiting toxicity observed.
The study demonstrated a favorable pharmacokinetic profile for niraparib, with dose-proportional increases in drug levels and some patients showing a partial response to treatment.
The safety, tolerability and pharmacokinetics of niraparib in Japanese patients with solid tumours: results of a phase I dose-escalation study.Yonemori, K., Shimizu, T., Kondo, S., et al.[2021]

References

Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE). [2021]
Buparlisib plus fulvestrant versus placebo plus fulvestrant for postmenopausal, hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer: Overall survival results from BELLE-2. [2019]
The safety, tolerability and pharmacokinetics of niraparib in Japanese patients with solid tumours: results of a phase I dose-escalation study. [2021]
Niraparib for Advanced Breast Cancer with Germline BRCA1 and BRCA2 Mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO Study. [2023]
Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. [2019]
A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4). [2020]
Genetic Alterations in the PI3K/AKT Pathway and Baseline AKT Activity Define AKT Inhibitor Sensitivity in Breast Cancer Patient-derived Xenografts. [2021]
BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population. [2023]