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Trial record 1 of 1 for:    NuTide:323
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A Study of NUC-3373 in Combination With Other Agents in Patients With Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT05678257
Recruitment Status : Active, not recruiting
First Posted : January 10, 2023
Last Update Posted : April 3, 2024
Sponsor:
Information provided by (Responsible Party):
NuCana plc

Brief Summary:

This is a randomized, open-label, dose/schedule optimization study comparing NUC-3373/leucovorin (LV)/irinotecan plus bevacizumab (NUFIRI-bev) to 5-FU/LV/irinotecan plus bevacizumab (FOLFIRI-bev) for the treatment of patients with unresectable metastatic colorectal cancer.

A total of 171 patients will be randomized 1:1:1 to either NUFIRI-bev on a weekly NUC-3373 schedule, NUFIRI-bev based on an alternate weekly NUC-3373 schedule, or FOLFIRI bev on an alternate weekly schedule. The main objectives are to assess and compare the efficacy and safety of the 3 regimens. Pharmacokinetics will be assessed on the 2 NUFIRI arms.


Condition or disease Intervention/treatment Phase
Colorectal Cancer Colorectal Neoplasms Colorectal Adenocarcinoma Colorectal Cancer Metastatic Neoplasm, Colorectal Drug: Fosifloxuridine Nafalbenamide Drug: Leucovorin Drug: Irinotecan Biological: Bevacizumab Drug: 5-FU Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 182 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomised, Open-label, Phase II, Dose/Schedule Optimisation Study of NUC-3373/Leucovorin/Irinotecan Plus Bevacizumab (NUFIRI-bev) Versus 5-FU/Leucovorin/Irinotecan Plus Bevacizumab (FOLFIRI-bev) for the Treatment of Patients With Previously Treated Unresectable Metastatic Colorectal Cancer
Actual Study Start Date : April 18, 2023
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: NUFIRI-bev on a Q1W NUC-3373 schedule

Arm A: Study treatment will be administered in 28-day cycles as follows:

  1. Bevacizumab 5 mg/kg on Days 1 and 15:

    • 90 minutes for the first dose
    • 60 minutes for the second dose (if first dose is tolerated)
    • 30 minutes for subsequent doses (if second dose is tolerated)
  2. LV 400 mg/m2 (or equivalent levo-LV) over 120 minutes on Days 1, 8, 15, and 22.
  3. Irinotecan 180 mg/m2 over 90 minutes (concurrently with the LV infusion) on Days 1 and 15.
  4. NUC-3373 1500 mg/m2 over 120 minutes on Days 1, 8, 15, and 22.
Drug: Fosifloxuridine Nafalbenamide
Intravenous infusion
Other Names:
  • NUC-3373
  • Nucleotide analogue

Drug: Leucovorin
Intravenous infusion
Other Names:
  • Folinic acid
  • LV

Drug: Irinotecan
Intravenous infusion
Other Names:
  • Campto
  • Camptosar

Biological: Bevacizumab
Intravenous infusion
Other Names:
  • Avastin
  • Zirabev

Experimental: NUFIRI-bev on a Q2W NUC-3373 schedule

Arm B: Study treatment will be administered in 28-day cycles as follows:

  1. Bevacizumab 5 mg/kg on Days 1 and 15:

    • 90 minutes for the first dose
    • 60 minutes for the second dose (if first dose is tolerated)
    • 30 minutes for subsequent doses (if second dose is tolerated)
  2. LV 400 mg/m2 (or equivalent levo-LV) over 120 minutes on Days 1 and 15.
  3. Irinotecan 180 mg/m2 over 90 minutes (concurrently with the LV infusion) on Days 1 and 15.
  4. NUC-3373 1500 mg/m2 over 120 minutes on Days 1 and 15.
Drug: Fosifloxuridine Nafalbenamide
Intravenous infusion
Other Names:
  • NUC-3373
  • Nucleotide analogue

Drug: Leucovorin
Intravenous infusion
Other Names:
  • Folinic acid
  • LV

Drug: Irinotecan
Intravenous infusion
Other Names:
  • Campto
  • Camptosar

Biological: Bevacizumab
Intravenous infusion
Other Names:
  • Avastin
  • Zirabev

Active Comparator: FOLFIRI-bev on a Q2W schedule

Arm C: Study treatment will be administered in 28-day cycles as follows:

  1. Bevacizumab 5 mg/kg on Days 1 and 15:

    • 90 minutes for the first dose
    • 60 minutes for the second dose (if first dose is tolerated)
    • 30 minutes for subsequent doses (if second dose is tolerated)
  2. LV 400 mg/m2 (or equivalent levo-LV) over 120 minutes on Days 1 and 15.
  3. Irinotecan 180 mg/m2 over 90 minutes (concurrently with the LV infusion) on Days 1 and 15.
  4. 5-FU 400 mg/m2 bolus on Days 1 and 15.
  5. 5-FU 2400 mg/m2 infusion over 46 hours on Days 1 and 15.
Drug: Leucovorin
Intravenous infusion
Other Names:
  • Folinic acid
  • LV

Drug: Irinotecan
Intravenous infusion
Other Names:
  • Campto
  • Camptosar

Biological: Bevacizumab
Intravenous infusion
Other Names:
  • Avastin
  • Zirabev

Drug: 5-FU
Intravenous infusion
Other Names:
  • 5FU
  • 5-fluorouracil
  • Fluorouracil




Primary Outcome Measures :
  1. Number of patients achieving progress-free survival (PFS) [ Time Frame: Assessed from baseline to 30 days after last dose of study drug ]
    PFS assessed according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, defined as the time from randomisation to the first observation of objective tumour progression or death from any cause


Secondary Outcome Measures :
  1. Number of patients achieving a reduction in tumour volume [ Time Frame: Assessed from baseline to 30 days after last dose of study drug ]
    Objective response rate, defined as the percentage of patients achieving a complete or partial (30%+) response to treatment

  2. Number of patients surviving [ Time Frame: Assessed from baseline to 30 days after last dose of study drug ]
    Overall survival, defined as the time from randomization to the time of death from any cause

  3. Number of patients reporting treatment-emergent adverse events (TEAEs) [ Time Frame: Assessed from baseline to 30 days after last dose of study drug ]
    TEAEs assessed and graded by CTCAE v5.0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of written informed consent.
  2. Histological or cytological confirmation of colorectal adenocarcinoma (excluding appendiceal and anal canal cancers, as well as signet-ring cell carcinoma) that is unresectable and metastatic.
  3. Measurable disease (as defined by RECIST v1.1).
  4. Received ≥2 months of a first-line fluoropyrimidine and oxaliplatin-containing regimen for metastatic disease or relapsed within 6 months of completing a fluoropyrimidine and oxaliplatin-containing neoadjuvant/adjuvant therapy. Previous treatment with standard of care chemotherapy regimens in combination with molecular targeted therapies (e.g., VEGF and EGFR pathway inhibitors and immuno-oncology agents) is permitted. Previous treatment with maintenance therapy (e.g., capecitabine) is also allowed. Patients who started on a fluoropyrimidine and oxaliplatin-containing regimen in any setting but must discontinue the oxaliplatin due to.toxicity or allergy (and are now unable to receive oxaliplatin) are considered eligible regardless of the number of cycles of oxaliplatin they received.
  5. Known RAS and BRAF status. Patients with wild-type RAS tumours must have received prior treatment with an EGFR inhibitor, unless this was not standard of care according to relevant region-specific treatment recommendations.
  6. Known UGT1A1 status, or patient consents to UGT1A1 status testing if unknown.
  7. Known DPD activity status, or patient consents to DPD status testing if unknown. See exclusion criterion 1.
  8. Age ≥18 years.
  9. Minimum life expectancy of ≥12 weeks.
  10. Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1.
  11. Adequate bone marrow function as defined by: absolute neutrophil count (ANC) ≥1.5 × 109/L, platelet count ≥100 × 109/L, and haemoglobin ≥9 g/dL. Patients with benign neutropenia may be discussed on a case-by-case basis with the medical monitor.
  12. Adequate liver function, as defined by: serum total bilirubin ≤1.5 × ULN), AST and ALT ≤2.5 × ULN (or ≤5 × ULN if liver metastases are present).
  13. Adequate renal function assessed as serum creatinine <1.5 × ULN and glomerular filtration rate ≥50 mL/min (calculated by the Cockcroft-Gault method).
  14. Serum albumin ≥3 g/dL.
  15. Ability to comply with protocol requirements.
  16. Female patients of child-bearing potential must have a negative serum 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 (defined in Section 10.3.1) or to use two forms of contraception, one of which must be highly effective. These forms of contraception must be used from the time of signing consent, throughout the treatment period, and for 6 months following the last dose of any study medication. Oral or injectable contraceptive agents cannot be the sole method of contraception
  17. Patients must have been advised to take measures to avoid or minimize exposure of the skin and eyes to UV light, including avoiding sunbathing and solarium use, for the duration of study participation and for a period of 4 weeks following the last dose of study medication

Exclusion Criteria:

  1. History of hypersensitivity or current contra-indications to 5-FU, FUDR, or capecitabine.
  2. History of hypersensitivity or current contra-indication to any of the combination agents required for the study.
  3. History of allergic reactions attributed to components of the NUC-3373 drug product formulation.
  4. History of hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies.
  5. History of or known central nervous system or leptomeningeal metastases.
  6. Symptomatic ascites, ascites currently requiring drainage procedures or ascites requiring drainage over the prior 3 months.
  7. Mutant BRAF V600E status.
  8. MSI high or dMMR.
  9. Prior treatment with irinotecan.
  10. Chemotherapy, hormonal therapy, radiotherapy (other than a short cycle of palliative radiotherapy [e.g., for bone pain]*), immunotherapy, biological agents, or exposure to another investigational agent within 21 days (or four times the half-life for molecular targeted agents, whichever is shorter) of first administration of study treatment:
  11. Residual toxicities from prior chemotherapy or radiotherapy which have not regressed to Grade ≤1 severity (CTCAE v5.0), except for alopecia and residual Grade 2 neuropathy.
  12. History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, surgically excised or potentially curatively treated ductal carcinoma in situ of the breast, or low-grade prostate cancer or patients after prostatectomy. Patients with previous invasive cancers are eligible if treatment was completed >3 years prior to initiating the current study treatment, and the patient has had no evidence or recurrence since then.
  13. Presence of an active bacterial or viral infection (including SARS-CoV-2, Herpes Zoster, Varicella Zoster or chickenpox), known Human Immunodeficiency Virus (HIV) positive or known active hepatitis B or C.
  14. 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 the patient's ability to participate in the study or with the interpretation of the results (refer to protocol for further details).
  15. Any condition that, in the judgment of the Investigator, may affect the patient's ability to provide informed consent and undergo study procedures.
  16. Patients with a history of haemoptysis (1/2 teaspoon or more of red blood) within 6 months prior to enrolment.
  17. Wound healing complications or surgery within 28 days of starting bevacizumab (wound healing must have been fully completed before starting bevacizumab). Investigators may allow patients to initiate treatment with the other study drugs (i.e., NUC-3373/5-FU, LV and irinotecan) on C1D1 but withhold bevacizumab for at least 15 days, but no longer than 28 days, to allow completion of wound healing in patients who would otherwise be eligible for the study, in line with standard local practice and after discussion with the Medical Monitor. Patients who have not received bevacizumab by C2D1 must be replaced.
  18. Unhealed wound, active gastric or duodenal ulcer, or bone fracture.
  19. Serious thromboembolic event in the 6 months before inclusion.
  20. Patients with a history of haemorrhage within 6 months prior to enrolment.
  21. Known inherited or acquired bleeding disorders.
  22. Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of packed RBC transfusions during the 4-week period prior to screening.
  23. Uncontrolled hypertension.
  24. Severe proteinuria or nephrotic syndrome.
  25. Acute intestinal obstruction or sub-obstruction, history of inflammatory intestinal disease or extended resection of the small intestine. Presence of a colic prosthesis.
  26. History of abdominal fistulas, trachea-oesophageal fistulas, any other Grade 4 gastrointestinal perforations, non-gastrointestinal fistulas, or intra-abdominal abscesses 6 months prior to screening.
  27. Currently pregnant, lactating or breastfeeding.
  28. Required concomitant use of brivudine, sorivudine and analogues.
  29. Required concomitant use of St John's Wort.
  30. Required concomitant use of drugs known to prolong QT/QTc interval.
  31. Required concomitant use of strong CYP3A4 inducers or strong CYP3A4 inhibitors. The use of strong CYP3A4 inducers within 2 weeks of first receipt of study drug or the use of strong CYP3A4 inhibitors within 1 week of first receipt of study drug is also excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05678257


Locations
Show Show 59 study locations
Sponsors and Collaborators
NuCana plc
Investigators
Layout table for investigator information
Study Director: Elisabeth Oelmann, MD, PhD NuCana plc
Layout table for additonal information
Responsible Party: NuCana plc
ClinicalTrials.gov Identifier: NCT05678257    
Other Study ID Numbers: NuTide:323
2022-001459-17 ( EudraCT Number )
First Posted: January 10, 2023    Key Record Dates
Last Update Posted: April 3, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by NuCana plc:
Relapsed metastatic adenocarcinoma of colon/rectum
NUC-3373
Fosifloxuridine nafalbenamide
Leucovorin
Irinotecan
Bevacizumab
Antineoplastic agents
Chemotherapy
Second-line chemotherapy
Locally advanced cancer
Metastatic cancer
Neoplasm
5-FU
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Colorectal Neoplasms
Adenocarcinoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Leucovorin
Bevacizumab
Fluorouracil
Irinotecan
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents