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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• NUC-3373 + leucovorin — DRUG
  NUC-3373 + leucovorin
• NUC-3373 — DRUG
  NUC-3373
• NUFOX — DRUG
  NUC-3373 + oxaliplatin
• NUFOX + VEGF pathway inhibitor — DRUG
  NUC-3373 + oxaliplatin + bevacizumab
• NUFOX + EGFR inhibitor — DRUG
  NUC-3373 + oxaliplatin + cetuximab/panitumumab
• NUFIRI — DRUG
  NUC-3373 + irinotecan
• NUFIRI + VEGF pathway inhibitor — DRUG
  NUC-3373 + irinotecan + bevacizumab
• NUFIRI + EGFR inhibitor — DRUG
  NUC-3373 + irinotecan + cetuximab/panitumumab
• NUC-3373 + bevacizumab — DRUG
  NUC-3373 + bevacizumab

Study Details

This is a three-part study of NUC-3373 administered by intravenous (IV) infusion across two administration schedules, either as monotherapy or as part of various combinations with agents commonly used to treat CRC (leucovorin, oxaliplatin, irinotecan, bevacizumab, cetuximab and panitumumab). The primary objective is to identify a recommended dose and schedule for NUC-3373 when combined with these agents.

Key Dates

First listed

Feb 12, 2018

Start date

Oct 5, 2018

Status verified

Mar 2025

Primary completion

Mar 19, 2024

Completion

Mar 21, 2024

Study Design

Enrollment

111 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: NUC-3373 + leucovorin (LV) every other week
  Arm 1a: NUC-3373 administered IV followed by a 2-week washout period. The next dose of NUC-3373 administered in combination with LV at 400 mg/m2. All subsequent doses of NUC-3373 administered in combination with LV every 2 weeks in 28-day cycles.
• Experimental: NUC-3373 every other week
  Arm 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 without LV in 28-day cycles.
• Experimental: NUC-3373 + leucovorin (LV) weekly
  Arm 1c: LV 400 mg/m2 administered IV over 2 hours followed by NUC-3373 administered IV weekly on Days 1, 8, 15 and 22 of 28-day cycles.
• Experimental: NUC-3373 + leucovorin (LV); combination chemotherapy ineligible
  Arm 1d: LV 400 mg/m2 administered IV over 2 hours followed by NUC-3373 administered IV on Days 1, 8, 15 and 22 of 28-day cycles.
• Experimental: NUC-3373 + oxaliplatin weekly
  Arm 2a: NUC-3373+LV (400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with oxaliplatin (85 mg/m2) administered on Days 1 and 15.
• Experimental: NUC-3373 + irinotecan weekly
  Arm 2b: NUC-3373+LV (400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with irinotecan (180 mg/m2) on Days 1 and 15.
• Experimental: NUC-3373 + oxaliplatin (NUFOX) expansion
  Arm 2c: At the completion of Arm 2a, the recommended dose of NUC-3373 (+LV 400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with oxaliplatin (85 mg/m2) administered on Days 1 and 15.
• Experimental: NUC-3373 + irinotecan (NUFIRI) expansion
  Arm 2d: At the completion of Arm 2b, the recommended dose of NUC-3373 (+LV 400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with irinotecan (180 mg/m2) on Days 1 and 15.
• Experimental: NUFOX + bevacizumab weekly
  Arm 3a: NUC-3373, LV and oxaliplatin at dose levels used in Arm 2a will be combined with bevacizumab. NUC-3373+LV will be administered weekly, oxaliplatin and bevacizumab will be administered every other week.
• Experimental: NUFOX + bevacizumab every other week
  Arm 3b: NUC-3373, LV and oxaliplatin at dose levels used in Arm 2a will be combined with bevacizumab. NUC-3373+LV+oxaliplatin+bevacizumab will be administered every other week.
• Experimental: NUFIRI + bevacizumab weekly
  Arm 3c: NUC-3373, LV and irinotecan at dose levels used in Arm 2b will be combined with bevacizumab. NUC-3373+LV will be administered weekly, irinotecan and bevacizumab will be administered every other week.
• Experimental: NUFIRI + bevacizumab every other week
  Arm 3d: NUC-3373, LV and irinotecan at dose levels used in Arm 2b will be combined with bevacizumab. NUC-3373+LV+irinotecan+bevacizumab will be administered every other week.
• Experimental: NUC-3373 + LV + bevacizumab; maintenance patients
  Arm 3e: NUC-3373+LV (400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with bevacizumab (administered every other week).
• Experimental: NUFOX + cetuximab
  Arm 3f: NUC-3373, LV and oxaliplatin at dose levels used in Arm 2a may be administered in subsequent cetuximab cohorts. NUC-3373+LV may be administered weekly or every other week, oxaliplatin will be administered every other week and cetuximab will be administered weekly.
• Experimental: NUFIRI + cetuximab
  Arm 3g: NUC-3373, LV and irinotecan at dose levels used in Arm 2b may be administered in subsequent cetuximab cohorts. NUC-3373+LV may be administered weekly or every other week, irinotecan will be administered every other week and cetuximab will be administered weekly.

Primary Outcome Measure

Percentage Change From Baseline in Tumour Size [ Time Frame: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months) ]

Locations (6)

Find similar trials in Boston, MA

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