NUC-1031 in Patients With Advanced Solid Tumours

NCT01621854 | Completed Phase 1 DMC

• 1 other identifier: PRO-001
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two-part Phase I, open label, dose-escalation, study of NUC-1031 as a single agent in patients with advanced solid tumours who have failed to respond to or who have relapsed after treatment with standard therapy. NUC-1031 is a ProTide of gemcitabine, a drug that has been used widely and effectively against cancers for many years. Both NUC-1031 and gemcitabine work by preventing cancer cells from dividing by attacking their DNA (deoxyribonucleic acid). Non clinical studies have shown that NUC-1031 is more effective than gemcitabine because it is able to reach cancer cells by passive diffusion, is less easily degraded by the cancer cell, and delivers the monophosphate form of the active agent. The first part of the study is to determine recommended phase 2 dose by dose escalation and the second part is to explore preliminary anti-tumour activity.

Conditions

Cancer

Keywords

cancer; nucleoside analogue; advanced solid tumours

Outcome Measures

Primary Outcomes (2)

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

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

  1.5 years

• To further evaluate the safety profile of NUC-1031 in an expanded cohort at RP2D

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

  1 year

Secondary Outcomes (2)

• To determine the pharmacokinetics of NUC-1031 and its metabolites.

  1.5 years

• To explore the preliminary anti-tumour activity of NUC-1031 [given at the RP2D and preferred schedule selected from Part I]

  1 year

Study Arms (1)

NUC-1031

EXPERIMENTAL

Cohort 1, Schedule A, NUC-1031 I.V. 1000mg/m2, Days 1, 8, \& 15 every 28 days Cohort 1, Schedule B, NUC-1031 I.V. 500mg/m2, Days 1 \& 5, 8 \& 12, 15 \&19 every 28 days Cohort 2, Schedule A, NUC-1031 I.V. 2000mg/m2, Days 1, 8, \& 15 every 28 days Cohort 2, Schedule B, NUC-1031 I.V. 1000mg/m2, Days 1 \& 5, 8 \& 12, 15 \&19 every 28 days

Drug: NUC-1031

Interventions

NUC-1031 DRUG

Cohort 1, Schedule A, NUC-1031 I.V. 1000mg/m2, Days 1, 8, \& 15 every 28 days Cohort 1, Schedule B, NUC-1031 I.V. 500mg/m2, Days 1 \& 5, 8 \& 12, 15 \&19 every 28 days Cohort 2, Schedule A, NUC-1031 I.V. 2000mg/m2, Days 1, 8, \& 15 every 28 days Cohort 2, Schedule B, NUC-1031 I.V. 1000mg/m2, Days 1 \& 5, 8 \& 12, 15 \&19 every 28 days

NUC-1031

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed written informed consent.
• Diagnosis: 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.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Life expectancy of ≥ 12 weeks.
• Disease measurability:
• Part I (Dose-escalation):
• Participants 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).
• Part II (expansion cohort):
• Participants must have at least one measurable disease lesion as per the RECIST criteria version 1.1.
• 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 ≥ 9g/dL.
• Adequate liver function, as determined by: Serum total bilirubin ≤1.5 x ULN.AST and ALT ≤ 2.5 x ULN..
• 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).
• Ability to comply with protocol requirements.
• Female participants 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 participants must be surgically sterile or agree to use a barrier method of contraception.

You may not qualify if:

• Participant with any of the following criteria will be excluded from the participation in the study:
• History of allergic reactions attributed to previous gemcitabine treatment.
• Symptomatic CNS or leptomeningeal metastases.
• Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy for bone pain), or immunotherapy within 28 days of first receipt of the IMP (within 6 weeks for nitrosoureas and mitomycin C). Hormone or biological therapy within 14 days of first receipt of IMP.
• Prior toxicities from chemotherapy or radiotherapy which have not regressed to Grade ≤ 1 severity (NCI-CTCAE version 4.0) apart from neuropathy and alopecia.
• Another active cancer (excluding basal cell carcinoma or cervical intraepithelial neoplasia (CIN/cervical in situ or melanoma in situ; part II only).
• Participants with uncontrolled concomitant illness, active infection requiring i.v. antibiotics.
• Participants will serious illnesses, medical conditions, or other medical history, including laboratory results, which, in the CI or delegates opinion would be likely to interfere with a participant's participation in the study, or with the interpretation of the results.
• Known HIV or known active Hepatitis B or C.
• Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc.) that, in the judgment of the CI or delegates may affect the participant's ability to sign the informed consent and undergo study procedures.

Sponsors & Collaborators

• Imperial College London: lead
• Nucana: collaborator

Study Sites (1)

NIHR/Wellcome Trust Imperial CRF

London, Hammersmith, W12 0HS, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

Interventions

NUC-1031

Study Officials

• Dr Blagden, PhD FRCP

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2012
• First Posted: June 18, 2012
• Study Start: October 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: March 20, 2024

Record last verified: 2024-03

Locations

GB (1)