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

• ClinicalTrials.gov Identifier: NCT03568422
• Recruitment Status: Active, not recruiting
• First Posted: June 26, 2018
• Last Update Posted: January 31, 2023
• Sponsor: Canadian Cancer Trials Group
• Collaborators: Stand Up To Cancer; Canadian Breast Cancer Foundation; Ontario Institute for Cancer Research
• Information provided by (Responsible Party): Canadian Cancer Trials Group

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: CFI-402257; Drug: Paclitaxel	Phase 1; Phase 2

Detailed Description:

Phase I:

The purpose of the first phase of the study is to find the highest dose of CFI-402257 that can be tolerated without causing very severe side effects when receiving paclitaxel. This is done by starting at a dose lower than the one that is tolerated in patients when given on its own. Participants are given CFI-402257 together with paclitaxel and are watched very closely to see what side effects they have and to make sure the side effects are not severe. If the side effects are not severe, then new participants will be given a higher dose of CFI-402257. Participants joining this study later on will get higher doses of CFI-402257 than participants who join earlier. This will continue until a dose is found that causes severe but temporary side effects. Doses higher than that will not be given.

Phase II:

The purpose of the second phase will be to find out the effect that CFI-402257 has on breast cancer, using doses found to be safe in the first phase of the study, when given with paclitaxel.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase Ib and Open Label Phase II Study of CFI-402257 in Combination With Weekly Paclitaxel in Patients With Advanced/Metastatic HER2-Negative Breast Cancer
• Actual Study Start Date: October 17, 2018
• Estimated Primary Completion Date: June 30, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: CFI-402257 + Paclitaxel; 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; Orally taken on intermittent schedule (days 1, 2, 8, 9, 15 & 16; Drug: Paclitaxel; 80 mg/m2 IV days 1, 8 & 15 every 28 days

Outcome Measures

Primary Outcome Measures :

1. Phase I: Safety and tolerability of CFI-402257 assessed by CTCAE [ Time Frame: 2 years ]
2. Phase I: Identify the recommended phase II dose [ Time Frame: 2 years ]
3. Phase II: Overall Response Rate using RECIST 1.1 [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. Clinical benefit rate determined by complete response, partial response or stable disease [ Time Frame: 2 years ]
   > 16 weeks in duration
2. Number and severity of adverse events by CTCAE [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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:

  1. they have relapsed within 6 months of completion of adjuvant/neoadjuvant chemotherapy and the regiment did not contain taxane, or,
  2. they have received taxane and/or anthracycline-containing adjuvant/neoadjuvant chemotherapy 6 or more months prior to relapse or;
  3. 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:

• Longest of one of the following:

  • Two weeks,
  • 5 half-lives for investigational agents,
  • Standard cycle length of standard therapies (e.g. at least 3 weeks for capecitabine.
• 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.
• Previous surgery is permitted provided that a minimum of 21 days (3 weeks) have elapsed between any major surgery and date of enrollment, and wound healing has occurred.
• Absolute neutrophils ≥ 1.5 x 10^9/L
• Platelets ≥100 x 10^9/L
• Bilirubin ≤ 1.0 x ULN
• AST and ALT ≤3.0 x ULN and ≤ 5.0 x ULN (if patient has liver mets)
• Serum creatinine ≤ 1.5 x ULN or
• Creatinine clearance ≥ 60mL/min
• Women of childbearing potential must have agreed to use a highly effective contraceptive method
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
• In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient enrollment.

Exclusion Criteria:

• 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.

Contacts and Locations

Locations

Canada, British Columbia

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada, V5Z 4E6

Canada, Ontario

Kingston Health Sciences Centre

Kingston, Ontario, Canada, K7L 2V7

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada, K1H 8L6

University Health Network

Toronto, Ontario, Canada, M5G 2M9

Sponsors and Collaborators

Canadian Cancer Trials Group

Stand Up To Cancer

Canadian Breast Cancer Foundation

Ontario Institute for Cancer Research

Investigators

• Study Chair: Philippe Bedard; Princess Margaret Cancer Centre, Toronto, ON
• Study Chair: Mihaela Mates; Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON

More Information

• Responsible Party: Canadian Cancer Trials Group
• ClinicalTrials.gov Identifier: NCT03568422
• Other Study ID Numbers: I236
• First Posted: June 26, 2018
• Last Update Posted: January 31, 2023
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action