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.
- 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:
- SECONDARY ID:
- NCT ID:
- Colorectal Cancer
- Colorectal Neoplasms
- Colorectal Carcinoma
- Colorectal Tumors
- Neoplasms, Colorectal
|NUC-3373 + leucovorin||folinic acid, levoleucovorin, Nucleotide analogue||NUC-3373+ leucovorin|
|NUC-3373 + oxaliplatin||Eloxatin, Nucleotide analogue||NUC-3373 + oxaliplatin|
|NUC-3373 + oxaliplatin + bevacizumab||Eloxatin, Avastin, Nucleotide analogue||NUC-3373 + oxaliplatin + bevacizumab|
|NUC-3373 + oxaliplatin + panitumumab||Eloxatin, Vectibix, Nucleotide analogue||NUC-3373 + oxaliplatin + panitumumab|
|NUC-3373 + irinotecan||Campto, Camptosar, Nucleotide analogue||NUC-3373 + irinotecan|
|NUC-3373 + irinotecan + cetuximab||Campto, Camptosar, Erbitux, Nucleotide analogue||NUC-3373 + irinotecan + cetuximab|
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.
|NUC-3373+ leucovorin||Experimental||Cohort 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||Experimental||Cohort 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 + oxaliplatin||Experimental||Cohort 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 + bevacizumab||Experimental||Cohort 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 + panitumumab||Experimental||Cohort 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 + irinotecan||Experimental||Cohort 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 + cetuximab||Experimental||Cohort 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
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.
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
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
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
|Maximum Eligible Age:||N/A|
|Minimum Eligible Age:||18 Years|
Primary Outcome Measures
|Measure:||Number of patients reporting treatment-emergent adverse events|
|Time Frame:||28 days|
|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|
|Description:||Dose intensity will be measured by the actual dose received as compared to the projected dose to be administered in Cycle 1|
|Lead Sponsor:||NuCana plc|
- Relapsed metastatic adenocarcinoma of colon/rectum
December 31, 2018