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

Trial Status: Active

This is a three-part study of NUC-3373 administered by intravenous (IV) infusion across two administration schedules, in separate combinations with leucovorin (LV), oxaliplatin, oxaliplatin and VEGF pathway inhibitors, oxaliplatin and EGFR inbibitors, irinotecan, irinotecan and VEGF pathway inhibitors, and irinotecan and EGFR inhibitors. The primary objective is to identify a recommended dose for NUC-3373 when combined with these agents.

Inclusion Criteria

  • Inclusion Criteria: 1. Provision of written informed consent 2. Have histological confirmation of locally advanced/unresectable or metastatic CRC 3. Must have received at least two prior lines of therapy for locally advanced/unresectable or metastatic CRC. 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. Previous treatment with standard of care chemotherapy regimens in combination with molecular targeted therapies (i.e therapies including VEGFR and EGFR pathway inhibitors and immuno-oncology agents) is permitted. 4. Age ≥18 years 5. Life expectancy of ≥12 weeks 6. ECOG Performance status 0 or 1 7. Measurable disease as defined by RECIST v1.1 8. Adequate bone marrow function as defined by: absolute neutrophil count ≥1.5×109/L and platelet count ≥100×109/L (with no evidence of bleeding) 9. Adequate liver function, as defined by: serum total bilirubin ≤1.5×upper limit of normal (ULN), aspartate aminotransferase and alanine aminotransferase ≤2.5×ULN (or ≤5×ULN if liver metastases are present) 10. Adequate renal function assessed as serum creatinine <1.5×ULN or glomerular filtration rate ≥50 mL/min 11. Serum albumin ≥3 g/dL 12. For the cohort in which the patient will participate, there are no contra-indications to receiving the approved partner combination drugs 13. Ability to comply with protocol requirements 14. Female patients of child-bearing potential must have a negative pregnancy test within 7 days prior to the first study drug administration. This criterion does not apply to patients who have had a previous hysterectomy or bilateral oophorectomy. Male patients and female patients of child-bearing potential must agree to practice true abstinence or to use two highly effective forms of contraception, one of which must be a barrier method. 15. Patients must have been advised to take measures to avoid or minimise exposure to UV light for the duration of study participation and for a period of 4 weeks following the last dose of study medication 16. For patients receiving oxaliplatin: Male patients must have been offered advice on and/or sought counselling for conservation of sperm prior to the first dose of study medication Exclusion Criteria: 1. Prior history of hypersensitivity or current contra-indications to 5-FU or capecitabine 2. Prior history of hypersensitivity or current contra-indications to any of the combination agents required for the study arm to which the patient is assigned 3. History of allergic reactions attributed to the components of the diluents used with NUC-3373 4. Symptomatic CNS or leptomeningeal metastases. 5. Symptomatic ascites, ascites currently requiring drainage procedures or ascites requiring drainage over the prior 3 months 6. Arm 3b and 3a only: mutant RAS or unknown RAS status 7. Chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy for bone pain), immunotherapy or exposure to another investigational agent within 28 days (or five times half-life for a biological agent) of first receipt of study drug 8. Residual toxicities from prior chemotherapy or radiotherapy, which have not regressed to Grade ≤1 severity (except for alopecia). In irinotecan cohorts residual Grade 2 neuropathy is allowed. 9. 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. 10. Presence of active bacterial or viral infection including Herpes Zoster or chicken pox 11. Presence of any uncontrolled concurrent 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 12. Known HIV positive or known active hepatitis B or C 13. 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 14. Currently pregnant, lactating or breastfeeding 15. QTc interval >450 milliseconds for males and >470 milliseconds for females 16. Required concomitant use of drugs known to prolong QT/QTc interval 17. Irinotecan cohorts: use of strong CYP3A4 inducers within 2 weeks of first dose of study drug or use of strong CYP3A4 or UGT1A1 inhibitors within 1 week of first dose of study drug 18. Has received a live vaccination within four weeks of first planned dose of study medication

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: ACTIVE
Massachusetts General Hospital Cancer Center
Status: ACTIVE

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: ACTIVE

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: ACTIVE

Trial Phase Phase I

Trial Type Treatment

Lead Organization
NuCana plc

  • Primary ID NuTide:302
  • Secondary IDs NCI-2018-02898, 2017-002062-53
  • Clinicaltrials.gov ID NCT03428958