Know Cancer

forgot password

A Two-part, Phase I Open Label Dose-escalation Study to Assess the Safety, Pharmacokinetics and Clinical Activity of NUC-1031, a Nucleoside Analogue, in Patients With Advanced Solid Tumours.

Phase 1
18 Years
Open (Enrolling)

Thank you

Trial Information

A Two-part, Phase I Open Label Dose-escalation Study to Assess the Safety, Pharmacokinetics and Clinical Activity of NUC-1031, a Nucleoside Analogue, in Patients With Advanced Solid Tumours.

This is a two-part, Phase I, open label study of NUC-1031 as a single agent, administered IV
weekly on days 1, 8, & 15 (Schedule A) or twice weekly on days 1 & 5, 8 & 12, 15 &19
(Schedule B) of a 28 day- cycle regimen. An initial dose-escalation phase (Part I) will be
followed by an expansion cohort phase (Part II) using the preferred regimen from Part 1. In
Part I, sequential patients will be assigned to increasing doses of NUC-1031 in a standard
'3 + 3' design to determine the recommended Phase II dose (RP2D). There will be a mandatory
review of all available data (in particular the safety profile and preliminary PK data
through to at least the last scheduled day of Cycle 1) following enrolment of the second
cohort of both schedule A and B to select the preferred administration schedule to take
forward for ongoing evaluation. Subsequently, safety review will be conducted prior to
enrolment of new subjects after every 2 planned dose levels and prior to definition of RP2D.

In Part II (dose expansion) additional patients will be enrolled to receive NUC-1031 at the
RP2D and dosing frequency determined from Part I of the study. To be eligible to enter Part
II, patients must have a diagnosis of cancer of the pancreas, ovary, lung (NSCL), breast, or
bladder. During Part II, further information will be obtained regarding safety, PK, PD and
preliminary anti-tumour efficacy of NUC-1031 at RP2D.

In both parts of the study, patients may continue to receive NUC-1031 for up to 6 cycles or
until disease progression, the occurrence of unmanageable drug related toxicity despite dose
modification or if the study participant declines further treatment.

Inclusion Criteria:

1. Provision of signed written informed consent.

2. Diagnosis:

1. Part I: Histologically or cytologically confirmed diagnosis of cancer which is
not amenable to standard therapy, is refractory to standard therapy or for which
no standard therapy exists.

2. Part II: Histologically or cytologically confirmed diagnosis of advanced or
metastatic cancer of the pancreas, ovary, lung (NSCL), breast, bladder or NHL
not amenable to standard therapy, refractory to standard therapy or for which no
standard therapy exists who have been previously treated with gemcitabine.

3. Age ≥ 18 years.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 5. Life
expectancy of ≥ 12 weeks.

6. Disease measurability:

1. Part I (Dose-escalation):

Patients must have a measurable (as per RECIST criteria version 1.1) and/or evaluable
disease (e.g., cytologically or radiologically detectable disease such as ascites,
peritoneal deposits, or lesions which do not fulfill RECIST criteria version 1.1 for
measurable disease).

2. Part II (expansion cohort):

Patients must have at least one measurable disease lesion as per the RECIST criteria
version 1.1.

7. Formalin Fixed Paraffin-Embedded (FFPE) archival tumour tissue available (for Part
II only). Fresh biopsies will be required if no FFPE tumour tissues available (for
Part II only).

8. Adequate bone marrow function as defined by: WBC of ≥ 3 x109/L, ANC of ≥ 1.5 x
109/L, platelet count of ≥ 100.0 x 109/L, and hemoglobin of ≥ 10 g/dL.

9. Adequate liver function, as determined by: Serum total bilirubin ≤1.5 x ULN (≤2.5
x ULN if liver metastases), AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases).

10. Adequate renal function assessed by at least one of the following: 1) Serum
creatinine ≤ 1.5 x ULN; or 2) creatinine clearance estimate of ≥ 60 mL/min in male
and ≥ 50 mL/min in female (as calculated according to Cockcroft-Gault formula).

11. Ability to comply with protocol requirements. 12. Female patients must be
postmenopausal (12 months of amenorrhea), surgically sterile or they must agree to
use a physical method of contraception. Oral or injectable contraceptive agents
cannot be the sole method of contraception. Male patients must be surgically sterile
or agree to use a barrier method of contraception.

13. Female patients of child-bearing potential must have a negative serum pregnancy
test within the seven days prior to the first study drug administration.

Exclusion Criteria:

1. History of allergic reactions attributed to previous gemcitabine treatment.

2. Symptomatic CNS or leptomeningeal metastases

3. Prior chemotherapy, radiotherapy (other than short cycle of palliative
radiotherapy for bone pain), or immunotherapy within 28 days of first receipt of
study drug (within 6 weeks for nitrosoureas and mitomycin C). Hormone therapy
within 14 days of first receipt of study drug.

4. Prior toxicities from chemotherapy or radiotherapy which have not regressed to
Grade ≤ 1 severity (NCI-CTCAE version 4.0) apart from neuropathy and alopecia.

5. Another active cancer (excluding basal cell carcinoma or cervical
intraepithelial neoplasia (CIN/cervical in situ or melanoma in situ; Part II

6. Patients with uncontrolled concomitant illness, active infection requiring i.v.
antibiotics, or uncontrolled infections, or a fever >38.5°C on the day of
scheduled dosing.

7. Patients will serious illnesses, medical conditions, or other medical history,
including laboratory results, which, in the investigator's opinion, would be
likely to interfere with a patient's participation in the study, or with the
interpretation of the results.

8. Known HIV or known active Hepatitis B or C.

9. 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.


Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the RP2D of NUC-1031 administered as either an I.V. weekly or twice-weekly schedule in patients with advanced solid tumours.

Outcome Description:

Adverse events (AE) and changes from baseline in vital signs, clinical laboratory parameters, and electrocardiography (ECG) assessments will be assessed

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Dr Blagden, PhD FRCP

Investigator Role:

Principal Investigator

Investigator Affiliation:

Imperial College London


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

October 2012

Completion Date:

December 2013

Related Keywords:

  • Cancer
  • cancer
  • nucleoside analogue
  • advanced solid tumours