CFI-402257 in Combination With Paclitaxel in Patients With Advanced/Metastatic HER2-Negative Breast Cancer

NCT03568422 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: I236
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 4

Brief Summary

The standard or usual treatment for this disease is to undergo chemotherapy to slow the spread of disease and relieve some symptoms of cancer. One of the standard types of chemotherapy is a drug called paclitaxel (Taxol) given in a low dose every week for three out of four weeks. CFI-402257 is a new type of drug for breast cancer. Laboratory tests show that it may help slow the growth of breast cancer. This drug has been shown to shrink tumours in animals. CFI-402257 has been studied in a few people and appears well tolerated with little side effects. CFI-402257 seems promising but it is not clear if it can offer better results when given with paclitaxel compared to paclitaxel alone.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Phase I: Recommended Phase II Dose for CFI-402257

  The maximum tolerated dose of CFI-402257 for phase II study identified by a standard 3+3 design to escalate the dose of CFI-402257.

  During cycle 1 (28 days)

• Phase II: Overall Response Rate Using RECIST 1.1

  Percentage of patients with a complete response (CR) or partial response (PR) 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; Overall Response (OR) = CR + PR.

  2 years

Secondary Outcomes (1)

• Phase II: Clinical Benefit Rate Determined by Complete Response, Partial Response or Stable Disease

  2 years

Study Arms (1)

CFI-402257 + Paclitaxel

EXPERIMENTAL

Oral CFI-402257 on intermittent schedule:\* days 1, 2, 8, 9, 15 \& 16 q4w Plus Paclitaxel 80 mg/m2 IV days 1, 8 \& 15 every 28 days

Drug: CFI-402257; Drug: Paclitaxel

Interventions

CFI-402257 DRUG

Orally taken on intermittent schedule (days 1, 2, 8, 9, 15 \& 16

CFI-402257 + Paclitaxel

Paclitaxel DRUG

80 mg/m2 IV days 1, 8 \& 15 every 28 days

CFI-402257 + Paclitaxel

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/recurrent or unresectable, for which no curative therapy exists, and for which systemic therapy is indicated. 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. Biopsies are optional but strongly encouraged for patients with accessible disease suitable for biopsy. The timing of tumour biopsies for patients who provide informed consent and are willing is prior to treatment (after enrollment) and again no later than the end of the day following the day 8 paclitaxel infusion. Lesions planned for biopsy may not be the only target lesion.
• 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). For phase Ib, patients are not required to have measurable disease as defined by RECIST 1.1 but must not have bone-only or marker only disease. For phase II, all patients must have measurable disease as defined by RECIST 1.1. The criteria for defining measurable disease are as follows:
• Chest xray ≥ 20mm; CT scan ≥ 10mm (longest diameter); Physical exam ≥10mm; Lymph nodes by CT scan ≥ 15mm (measured in short axis)
• Patients must be ≥18 years of age.
• Patients must have an ECOG performance status of 0 or 1.
• Patients must be able to swallow oral medications
• Patients must have received at least one non-taxane containing chemotherapy regimen for advanced or metastatic disease unless:
• they have relapsed within 6 months of completion of adjuvant/neoadjuvant chemotherapy and the regiment did not contain taxane, or,
• they have received taxane and/or anthracycline-containing adjuvant/neoadjuvant chemotherapy 6 or more months prior to relapse or;
• they have a documented contraindication to palliative chemotherapy other than weekly paclitaxel.
• Patients must not be considered appropriate for endocrine therapy and must not have received taxanes in the metastatic setting.
• Patients may have received other therapies including endocrine therapy, immunotherapy, and/or targeted therapies (including CDK4/6 inhibitors).
• Patient may NOT have had previous exposure to any therapy within the pharmacological class (TTK/MPS1 inhibitor).
• Patients must have recovered (to at least grade 0 or 1) from all reversible toxicity other than alopecia related to prior chemotherapy or systemic therapy and have adequate washout as follows:

You may not qualify if:

• Patients with a history of other untreated malignancies or malignancies which required therapy within the past 2 years. Patients with other malignancies of a nature that do not require treatment may be eligible after consultation with the CCTG.
• Patients with HER2 positive breast cancer.
• Patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol.
• 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 ahve a LVEF ≥ 50%
• Patients are not eligible if they have a known hypersensitivity to the study drug(s) or their components.
• Patients with history of central nervous system metastases or spinal cord compression unless have received definitive treatment, are clinically stable and do not require corticosteroids.
• Patients who have contraindications to treatment with paclitaxel and/or neuropathy \> grade 1.
• Concurrent treatment with other investigational drugs or anti-cancer therapy.
• Pregnant or breastfeeding women.
• Prohibited medications as listed in Appendix V Table 1
• Patients treated with full-dose warfarin. 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.
• Patients with a medical condition that could 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
• Stand Up To Cancer: collaborator
• Ontario Institute for Cancer Research: collaborator
• Canadian Breast Cancer Foundation: collaborator

Study Sites (4)

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, 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

CFI-402257; Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Pierre-Olivier Gaudreau
• Organization: Canadian Cancer Trials Group

p-ogaudreau@ctg.queensu.ca

6135336430

Study Officials

• Philippe Bedard

  Princess Margaret Cancer Centre, Toronto, ON

  STUDY CHAIR

• Mihaela Mates

  Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON

  STUDY CHAIR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: June 13, 2018
• First Posted: June 26, 2018
• Study Start: February 5, 2019
• Primary Completion: November 21, 2022
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 27, 2026
• Results First Posted: June 26, 2024

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)