A Phase I Study of CX5461

NCT02719977 | Completed Phase 1 DMC

• 1 other identifier: I231
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Cancer

Outcome Measures

Primary Outcomes (1)

• Confirm the recommended phase II dose and schedule of CX5461 in patients with solid tumours

  12 months

Secondary Outcomes (2)

• Number and severity of adverse events in patients

  12 months

• Assess pharmacokinetics of CX5461

  12 months

Study Arms (1)

CX-5461

EXPERIMENTAL

CX5461 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

Drug: CX5461

Interventions

CX5461 DRUG

CX-5461

Eligibility Criteria

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

You may qualify if:

• \- 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.

You may not qualify if:

• \- 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.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Senhwa Biosciences, Inc.: collaborator
• Stand Up To Cancer: collaborator

Study Sites (3)

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (2)

• Hilton J, Gelmon K, Bedard PL, Tu D, Xu H, Tinker AV, Goodwin R, Laurie SA, Jonker D, Hansen AR, Veitch ZW, Renouf DJ, Hagerman L, Lui H, Chen B, Kellar D, Li I, Lee SE, Kono T, Cheng BYC, Yap D, Lai D, Beatty S, Soong J, Pritchard KI, Soria-Bretones I, Chen E, Feilotter H, Rushton M, Seymour L, Aparicio S, Cescon DW. Results of the phase I CCTG IND.231 trial of CX-5461 in patients with advanced solid tumors enriched for DNA-repair deficiencies. Nat Commun. 2022 Jun 24;13(1):3607. doi: 10.1038/s41467-022-31199-2.

  PMID: 35750695 RESULT

• Xu H, Di Antonio M, McKinney S, Mathew V, Ho B, O'Neil NJ, Santos ND, Silvester J, Wei V, Garcia J, Kabeer F, Lai D, Soriano P, Banath J, Chiu DS, Yap D, Le DD, Ye FB, Zhang A, Thu K, Soong J, Lin SC, Tsai AH, Osako T, Algara T, Saunders DN, Wong J, Xian J, Bally MB, Brenton JD, Brown GW, Shah SP, Cescon D, Mak TW, Caldas C, Stirling PC, Hieter P, Balasubramanian S, Aparicio S. CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours. Nat Commun. 2017 Feb 17;8:14432. doi: 10.1038/ncomms14432.

  PMID: 28211448 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

CX 5461

Study Officials

• Karen Gelmon

  BCCA - Vancouver Cancer Centre

  STUDY CHAIR

• John Hilton

  Ottawa Hospital Research Institute

  STUDY CHAIR

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: March 21, 2016
• First Posted: March 25, 2016
• Study Start: June 13, 2016
• Primary Completion: January 30, 2020
• Study Completion: January 18, 2023
• Last Updated: August 4, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)