CFI-400945 and Durvalumab in Patients With Advanced Triple Negative Breast Cancer

NCT04176848 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: I239
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to find out the effect that CFI-400945 and durvalumab have on breast cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Defined as percentage of participants with objective response over all participants enrolled. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.

  24 months

Secondary Outcomes (2)

• Disease Control Rate

  24 months

• Immune-Related Response Rate (iRECIST) of CFI-400945 Given With Durvalumab

  24 months

Study Arms (1)

CFI-400945 + Durvalumab

EXPERIMENTAL

CFI-400945 32 mg orally on Days 1-7 and Days 15-21 of Cycle 1 (28 day cycle) and then daily from Cycle 2 on and Durvalumab 1500mg IV on Day 1 (28 day cycles) from Cycle 2 on.

Drug: CFI-400945; Drug: Durvalumab

Interventions

CFI-400945 DRUG

CFI-400945 32 mg: Cycle 1: Days 1-7, then Days 15-21; Cycle 2 on: orally once daily

CFI-400945 + Durvalumab

Durvalumab DRUG

Cycle 2 on: Durvalumab 1500mg IV on Day 1 (28 day cycles)

Also known as: IMFINZI

CFI-400945 + Durvalumab

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically and/or cytologically confirmed diagnosis of breast cancer, that is advanced/metastatic or unresectable, for which no curative therapy exists, and be negative for ER, PR and HER2 by ASCO/CAP criteria on the most recent sample. Patients with tumour with either low (\< 10%) ER expression who are PR and HER2 negative, or ER and HER2 negative but with low PR (\< 10%) may be enrolled after discussion and confirmation with CCTG
• Only female patients will be enrolled
• 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.
• 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 of 0 or 1
• Patients must have a life expectancy of 3 months or longer
• Laboratory Requirements (must be done within 7 days prior to enrollment) Absolute neutrophils ≥ 1.5 x 10\^9/L Platelets ≥ 100 x 10\^9/L Bilirubin ≤ 1.5 x ULN (upper limit of normal) AST and ALT ≤ 2.5 x ULN, ≤ 4.0 x ULN if patient has liver metastases Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 50 mL/min
• Patients must be able to swallow oral medications and have no known gastrointestinal disorders that may interfere with absorption (such as malabsorption).
• Patients must have had at least 1 prior line of cytotoxic chemotherapy for breast cancer, in any setting, which must have included an anthracycline and a taxane (unless contraindicated). Select patients that have not received both anthracycline and taxane therapy may be considered eligible after discussion with CCTG. There is no limit to the number of prior chemotherapy regimens.

You may not qualify if:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for \> 2 years and which do not require ongoing treatment.
• Patients with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol (including corticosteroid administration), or would put the patient at risk. This includes but is not limited to:
• History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements.
• Active infection requiring systemic therapy; (including any patient known to have active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or tuberculosis or any infection requiring systemic therapy).
• Active peptic ulcer disease or gastritis.
• Known pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function.
• Patients with diabetes mellitus are eligible but must be clinically stable on therapy (if applicable) and investigator and patient should be aware of the potential risk of immune mediated pancreatic toxicity and B cell destruction.
• Patients are not eligible if they have a known hypersensitivity to the study drug(s) or their components.
• Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if controlled, should have a LVEF ≥ 50%.
• 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 who have received growth factors within 28 days prior to initiation of dosing of CFI- 400945 or who will require treatment with growth factors throughout the duration of the trial.
• Pregnant or breastfeeding women.
• Patients being treated with drugs listed in Appendix VI Table 1 are excluded. Patients being treated with drugs listed in Appendix VI Table 2 may be enrolled, but should be monitored carefully for toxicities resulting from potential interactions between CFI-400945 and these drugs. In addition, patients must avoid consumption of the fruit or juice of Seville oranges (e.g. marmalade), grapefruit, pomelos and star fruit from 7 days before the first dose of study drug and during the entire study due to potential CYP3A4 interaction with the study drug. Regular orange juice is allowed.
• Patients with history of central nervous system metastases or spinal cord compression unless they have received definitive treatment, are clinically stable and do not require corticosteroids.
• Patients with any medical condition that would impair the administration of oral agents including significant bowel resection, inflammatory bowel disease or uncontrolled nausea or vomiting.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• AstraZeneca: collaborator
• University Health Network, Toronto: collaborator

Study Sites (5)

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

2-(3-(4-((2,6-dimethylmorpholino)methyl)styryl)-1H-indazol-6-yl)-5'-methoxyspiro(cyclopropane-1,3'-indolin)-2'-one; durvalumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Lesley Seymour
• Organization: Canadian Cancer Trials Group

lseymour@ctg.queensu.ca

6135336430

Study Officials

• David Cescon

  University Health Network, PMH, Toronto ON

  STUDY CHAIR

• Andrew Robinson

  Cancer Centre of Southeastern Ontario at Kingston, ON

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2019
• First Posted: November 25, 2019
• Study Start: August 10, 2020
• Primary Completion: September 15, 2022
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 18, 2026
• Results First Posted: August 9, 2024

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5)