Clinical Trials /

A Phase I Study of CX5461

NCT02719977

Description:

CX5461 is a new type of drug for many types of cancer, particularly cancers that cannot easily repair damage to their cells. This may help to slow down the growth of cancer or may cause cancer cells to die. CX5461 has been shown to shrink tumours in animals and has been studied in a few people and seems promising but it is not clear if it can offer better results than standard treatment.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase I Study of CX5461
  • Official Title: A Phase I Study of CX5461

Clinical Trial IDs

  • ORG STUDY ID: I231
  • NCT ID: NCT02719977

Conditions

  • Cancer

Interventions

DrugSynonymsArms
CX5461CX-5461

Purpose

CX5461 is a new type of drug for many types of cancer, particularly cancers that cannot easily repair damage to their cells. This may help to slow down the growth of cancer or may cause cancer cells to die. CX5461 has been shown to shrink tumours in animals and has been studied in a few people and seems promising but it is not clear if it can offer better results than standard treatment.

Detailed Description

      The purpose of this study is to find the dose of a new therapy, CX5461, that can be tolerated
      without causing very severe side effects and to see what effects the study drug has this
      cancer. Participants are given CX5461 and are watched very closely to see what side effects
      they have and to make sure the side effects are not severe. If serious side effects are seen
      in patients at the first dose level, doses of CX5461 may be lowered in subsequent patients.
      If the side effects are not serious, then more participants are asked to join this study and
      are given higher doses. This will continue until a dose is found that causes severe but
      temporary side effects. Doses higher than that will not be given.
    

Trial Arms

NameTypeDescriptionInterventions
CX-5461ExperimentalCX5461 as intravenous infusion on day 1 and day 8 every 4 weeks. A day 1 every 3 weeks schedule may be used if the day 1 and day 8 every 4 weeks schedule is not tolerable
  • CX5461

Eligibility Criteria

        Inclusion Criteria:

        - Tumour Type Phase I Escalation: Patients must have histologically/and or cytologically
        confirmed solid malignancy that is advanced/metastatic/recurrent or unresectable and for
        which no curative therapy exists.

        Phase I Expansion: Patients must have metastatic/recurrent/locally advanced/unresectable
        breast cancer with known BRCA1/2 or HRD germline aberrations.

          -  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. All patients must also have provided informed consent for a
             whole blood sample (after implementation of amendment 3).

          -  All patients enrolled after the implementation of Amendment 2 must also have provided
             informed consent for, and be willing to undergo, a skin biopsy (of an area including
             hair follicles, that is not sun-exposed) prior to treatment (after registration) and
             after cycle 1 day 15 (C1D16). Paired tumour biopsies will also be required for 6-8
             patients enrolled to the RP2D expansion. Note: During accrual to this portion of the
             study, it may be necessary to restrict accrual to patients who are suitable for, and
             have consented to, tumour and skin biopsies. Paired tumour biopsies are strongly
             recommended for all patients

          -  Patients must be ≥ 18 years of age.

          -  Patients must have an ECOG performance status of 0, 1, or 2.

          -  Presence of clinically and/or radiologically documented disease. All radiology studies
             must be performed within 28 days prior to registration (within 35 days if negative).

               -  Phase I: patients do not need to have measurable disease

               -  Phase I Expansion: patients must have measurable disease

          -  Previous Therapy

        Cytotoxic Chemotherapy:

          -  Phase I: There is no limit to the number of prior regimens received.

          -  Phase I Expansion: Patients must have received at least one but no more than 3
             regimens for advanced disease (Note: adjuvant anthracycline/taxane containing
             chemotherapy is considered an advanced regimen) Note: initially, there is no
             limitation to the use of prior platinumor PARPi containing regimens. During the
             expansion accrual may be limited to patients considered to be platinum naive, or
             platinum sensitive (no evidence of disease progression on or within 3 months of the
             last dose) or PARPi naïve or exposed. Sites will be informed at the time of the
             opening of the cohorts

        Other Systemic Therapy:

        • There is no limit to the number of prior therapies.

        Patients must have recovered (to baseline or ≤ grade 1) from all reversible toxicity
        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.

        Radiation:

        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 registration. Exceptions may be made
        for low-dose, non-myelosuppressive radiotherapy after consultation with CCTG. Concurrent
        radiotherapy is not permitted.

        Surgery:

        Previous surgery is permitted provided that a minimum of 28 days (4 weeks) have elapsed
        between any major surgery and date of registration, and that wound healing has occurred.

          -  Lab Requirements Absolute neutrophils: ≥ 1.5 x 10^9/L Platelets: ≥ 100 x 10^9/L
             Bilirubin: ≤ 1.5 x ULN (upper limit of normal) AST/ALT: ≤ 2.5 x ULN ≤ 5.0 x ULN if
             patient has liver metastases Serum creatinine: ≤ 1.25 x ULN Creatinine clearance: ≥ 50
             mL/min

          -  Women/men of childbearing potential must have agreed to use two effective
             contraceptive methods while on study and for 6 months after the last dose of CX5461.

          -  Patient consent must be appropriately obtained in accordance with applicable local and
             regulatory requirements.

          -  Patients must be accessible for treatment and follow up.

          -  Treatment is to begin within 2 working days of patient registration.

        Exclusion Criteria:

        - Other Malignancies

        Phase I - Patients with other malignancies requiring concurrent anticancer therapy.

        Phase I Expansion - Patients with a history of other malignancies, except:

          -  adequately treated non-melanomatous skin cancer,

          -  curatively treated in-situ cancer, or

          -  other solid tumours curatively treated at least 2 years prior to registration with no
             evidence of disease and not requiring concurrent anticancer treatment.

               -  Patients with symptomatic brain metastases or spinal cord compression. Patients
                  with asymptomatic brain/spinal cord metastasis who are not planned for radiation,
                  or who have been treated and are stable off steroids (or on a decreasing dose)
                  and anticonvulsants are eligible.

               -  History of hypersensitivity to CX5461 or any excipient.

               -  Patients with known photosensitivity disorders (xeroderma pigmentosa, porphyria
                  etc). Patients who do not agree to use sunglasses and sun blocker (with SPF >30
                  to UVB and a high degree of protection against UVA) if exposed to sunlight during
                  the course of the study and for 3 months after the last dose. Patients who plan
                  to use sun beds or tanning booths during the course of the study and within 3
                  months after the last dose are not eligible.

               -  Patients who have untreated and/or uncontrolled cardiovascular conditions
                  documented within the last year:

          -  unstable angina,

          -  congestive heart failure,

          -  myocardial infarction,

          -  cardiac ventricular arrhythmias requiring medication,

          -  history of 2nd or 3rd degree atrioventricular conduction defects.

        Patients who do not have untreated or uncontrolled cardiovascular conditions within the
        last year must have a LVEF ≥ 50%.

          -  Concurrent treatment with other investigational drugs or anti-cancer therapy.

          -  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.

          -  Pregnant or lactating women.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirm the recommended phase II dose and schedule of CX5461 in patients with solid tumours
Time Frame:12 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number and severity of adverse events in patients
Time Frame:12 months
Safety Issue:
Description:To establish the safety and tolerability of CX5461 given intravenously to patients with solid tumours.
Measure:Assess pharmacokinetics of CX5461
Time Frame:12 months
Safety Issue:
Description:To determine the pharmacokinetics of CX5461 given intravenously to patients with solid tumours

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Canadian Cancer Trials Group

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