Clinical Trials /

A Safety Study of NUC-3373 in Combination With Standard Agents Used in Colorectal Cancer Treatment

NCT03428958

Description:

This is a two-part study of NUC-3373 administered every 2 weeks as an intravenous infusion, in separate combinations with leucovorin, oxaliplatin, oxaliplatin + bevacizumab, oxaliplatin + panitumumab, irinotecan, and irinotecan + cetuximab. The primary objective is to identify a recommended dose for NUC-3373 when combined with these agents.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Safety Study of NUC-3373 in Combination With Standard Agents Used in Colorectal Cancer Treatment
  • Official Title: A Phase Ib Open Label Study to Assess the Safety and Pharmacokinetics of NUC-3373, a Nucleotide Analogue, Given in Combination With Standard Agents Used in Colorectal Cancer Treatment

Clinical Trial IDs

  • ORG STUDY ID: NuTide:302
  • SECONDARY ID: 2017-002062-53
  • NCT ID: NCT03428958

Conditions

  • Colorectal Cancer
  • Colorectal Neoplasms
  • Colorectal Carcinoma
  • Colorectal Tumors
  • Neoplasms, Colorectal

Interventions

DrugSynonymsArms
NUC-3373 + leucovorinfolinic acid, levoleucovorin, Nucleotide analogueNUC-3373+ leucovorin
NUC-3373Nucleotide analogueNUC-3373
NUC-3373 + oxaliplatinEloxatin, Nucleotide analogueNUC-3373 + oxaliplatin
NUC-3373 + oxaliplatin + bevacizumabEloxatin, Avastin, Nucleotide analogueNUC-3373 + oxaliplatin + bevacizumab
NUC-3373 + oxaliplatin + panitumumabEloxatin, Vectibix, Nucleotide analogueNUC-3373 + oxaliplatin + panitumumab
NUC-3373 + irinotecanCampto, Camptosar, Nucleotide analogueNUC-3373 + irinotecan
NUC-3373 + irinotecan + cetuximabCampto, Camptosar, Erbitux, Nucleotide analogueNUC-3373 + irinotecan + cetuximab

Purpose

This is a two-part study of NUC-3373 administered every 2 weeks as an intravenous infusion, in separate combinations with leucovorin, oxaliplatin, oxaliplatin + bevacizumab, oxaliplatin + panitumumab, irinotecan, and irinotecan + cetuximab. The primary objective is to identify a recommended dose for NUC-3373 when combined with these agents.

Trial Arms

NameTypeDescriptionInterventions
NUC-3373+ leucovorinExperimentalCohort 1a: NUC-3373 administered intravenously (IV) followed by a 2-week washout period. Then, LV 400 mg/m2 IV over 2 hours prior to each NUC-3373 infusion and NUC-3373 administered IV every 2 weeks.
  • NUC-3373 + leucovorin
NUC-3373ExperimentalCohort 1b: LV 400 mg/m2 administered IV over 2 hours prior to NUC-3373 infusion followed by a 2-week washout period. Then, NUC-3373 administered IV every 2 weeks.
  • NUC-3373
NUC-3373 + oxaliplatinExperimentalCohort 2a: NUC-3373 administered every 2 weeks in combination with oxaliplatin (85 mg/m2). Leucovorin may also be administered with this combination, depending on data from Part 1.
  • NUC-3373 + oxaliplatin
NUC-3373 + oxaliplatin + bevacizumabExperimentalCohort 2b: NUC-3373 administered every 2 weeks in combination with oxaliplatin (85 mg/m2) and bevacizumab (5 mg/kg). Leucovorin may also be administered with this combination, depending on data from Part 1.
  • NUC-3373 + oxaliplatin + bevacizumab
NUC-3373 + oxaliplatin + panitumumabExperimentalCohort 2c: NUC-3373 administered every 2 weeks in combination with oxaliplatin (85 mg/m2) and panitumumab (6 mg/kg). Leucovorin may also be administered with this combination, depending on data from Part 1.
  • NUC-3373 + oxaliplatin + panitumumab
NUC-3373 + irinotecanExperimentalCohort 3a: NUC-3373 administered every 2 weeks in combination with irinotecan (180 mg/m2). Leucovorin may also be administered with this combination, depending on data from Part 1.
  • NUC-3373 + irinotecan
NUC-3373 + irinotecan + cetuximabExperimentalCohort 3b: NUC-3373 administered every 2 weeks in combination with irinotecan (180 mg/m2) and cetuximab 400 mg/m2 (first dose) and 250 mg/m2 (subsequent doses). Cetuximab is administered weekly. Leucovorin may also be administered with this combination, depending on data from Part 1.
  • NUC-3373 + irinotecan + cetuximab

Eligibility Criteria

        Inclusion Criteria:

          1. Provision of signed written informed consent.

          2. Have histological confirmation of locally advanced/unresectable or metastatic
             colorectal cancer, with evidence of disease recurrence.

          3. Have relapsed on or after at least at least two prior lines of therapy for locally
             advanced/unresectable or metastatic colorectal cancer. One prior line of therapy must
             be an oxaliplatin + 5-FU containing regimen and one prior line of therapy must be an
             irinotecan + 5-FU containing regimen.

          4. Age ≥18 years.

          5. ECOG Performance status 0 or 1.

          6. Measurable disease as defined by RECIST.

        Exclusion Criteria:

          1. Prior history of hypersensitivity or current contraindications to 5-FU or capecitabine
             or the combination agent to be used.

          2. History of allergic reactions attributed to the components of the diluents used with
             NUC-3373.

          3. Symptomatic CNS or leptomeningeal metastases.

          4. Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy
             for bone pain), treatment with a VEGF inhibitor, EGF inhibitor or immunotherapy within
             21 days of first receipt of study drug.

          5. Residual toxicities from chemotherapy or radiotherapy, which have not regressed to
             Grade ≤1 severity (CTCAE v4.03), except for alopecia. In Cohorts 1a, 1b, 3a, and 3b,
             residual Grade 2 neuropathy is allowed.

          6. History of another malignancy diagnosed within the past 5 years, with the exception of
             adequately treated non-melanoma skin cancer curatively treated carcinoma in situ of
             the cervix or ductal carcinoma in situ (DCIS) of the breast. Patients with previous
             invasive cancers are eligible if treatment was completed more than 5 years prior to
             initiating the current study treatment, and the patient has had no evidence of
             recurrence since then.

          7. Presence of active bacterial or viral infection including Herpes Zoster or chicken
             pox.

          8. Presence of any serious uncontrolled concomitant illness, serious illness, medical
             condition, or other medical history, including laboratory results, which, in the
             Investigator's opinion, would be likely to interfere with their participation in the
             study, or with the interpretation of the results.

          9. Known HIV positive or known active hepatitis B or C.

         10. Any condition (e.g. known or suspected poor compliance, psychological instability,
             geographical location, etc.) that, in the judgment of the Investigator, may affect the
             patient's ability to sign the informed consent and undergo study procedures.

         11. Currently pregnant, lactating or breastfeeding.

         12. QTc interval >450 milliseconds for males and >470 milliseconds for females.

         13. Concomitant use of drugs known to prolong QT/QTc interval.

         14. Have received a live vaccination within four weeks of first planned dose of study
             medication.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients reporting treatment-emergent adverse events
Time Frame:28 days
Safety Issue:
Description:Treatment-emergent adverse events will be assessed and graded by CTCAE 4.0

Secondary Outcome Measures

Measure:Tolerability of NUC-3373 in each combination cohort measured by dose intensity in Cycle 1
Time Frame:28 days
Safety Issue:
Description:Dose intensity will be measured by the actual dose received as compared to the projected dose to be administered in Cycle 1

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NuCana plc

Trial Keywords

  • Relapsed metastatic adenocarcinoma of colon/rectum

Last Updated

December 31, 2018