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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03568422
Recruitment Status : Recruiting
First Posted : June 26, 2018
Last Update Posted : August 14, 2019
Sponsor:
Collaborators:
Stand Up To Cancer
Canadian Breast Cancer Foundation
Ontario Institute for Cancer Research
Information provided by (Responsible Party):
Canadian Cancer Trials Group

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
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 : July 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Paclitaxel

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




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 ]
  3. Pharmacokinetic analysis (AUC) using ANOVA and linear regression or comparable nonparametric statistical methods will be used to make dose group comparisons. [ Time Frame: 2 years ]
  4. Pharmacokinetic analysis (Cmax) using ANOVA and linear regression or comparable nonparametric statistical methods will be used to make dose group comparisons. [ Time Frame: 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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
  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03568422


Contacts
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Contact: Lesley Seymour 613-533-6430 lseymour@ctg.queensu.ca

Locations
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Canada, British Columbia
BCCA - Vancouver Cancer Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Karen Gelmon    604 877-6000 ext 2032      
Canada, Ontario
Kingston Health Sciences Centre Recruiting
Kingston, Ontario, Canada, K7L 2V7
Contact: Mihaela Mates    613 549-2631 ext 77725      
Ottawa Hospital Research Institute Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: John Hilton    613 737-7700 ext 75086      
University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Philippe Bedard    416 946-4501 ext 4534      
Sponsors and Collaborators
Canadian Cancer Trials Group
Stand Up To Cancer
Canadian Breast Cancer Foundation
Ontario Institute for Cancer Research
Investigators
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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

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Responsible Party: Canadian Cancer Trials Group
ClinicalTrials.gov Identifier: NCT03568422    
Other Study ID Numbers: I236
First Posted: June 26, 2018    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action