CancerPhase 1ProGem1NCT01621854
NUC-1031 in Patients With Advanced Solid Tumours
A Phase 1 study testing NUC-1031 in people with Cancer, run by Imperial College London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- NUC-1031
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2012to Jun 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
- Female participants of child-bearing potential must have a negative serum pregnancy test within the seven days prior to the first IMP administration.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
NIHR/Wellcome Trust Imperial CRF
London, Hammersmith, W12 0HS
About this study
Official title: A Two-part, Phase I Open Label Dose-escalation Study to Assess the Safety, Pharmacokinetics and Clinical Activity of NUC-1031, a Nucleotide Analogue, in Patients With Advanced Solid Tumours.
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.
Read the detailed description
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 I. 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 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.
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. 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, until disease progression, for as long as the participant receives clinical benefit in the opinion of the CI, the occurrence of unmanageable drug related toxicity despite dose modification or if the study participant declines further treatment.
- Conditions
- Cancer
- Being tested
- NUC-1031
- Keywords
- cancer, nucleoside analogue, advanced solid tumours
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NUC-1031Drug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: NUC-1031 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 1 year
Secondary outcomes (2)
To determine the pharmacokinetics of NUC-1031 and its metabolites.
PK endpoints will include assessments such as systemic Clearance (CL), Apparent Volume of Distribution (Vd), Area Under the Curve (AUC), Maximum plasma (peak) drug concentration after single dose administration (Cmax), and t1/2.
Measured: 1.5 years
To explore the preliminary anti-tumour activity of NUC-1031 [given at the RP2D and preferred schedule selected from Part I]
Assessment of anti-tumour activity as defined by RECIST version 1.1
Urinary excretion of NUC-1031 and metabolites.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2012 (estimated)
- Study startOct 2012
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Nucana
- Responsible party
- Sponsor
- Investigators
- Dr Blagden, PhD FRCP, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01621854
- Sponsor's protocol ID
- PRO-001
- Acronym
- ProGem1
- Status last verified
- Mar 2024
- First submitted
- 14 Jun 2012
- Last updated
- 20 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-part, Phase I Open Label Dose-escalation Study to Assess the Safety, Pharmacokinetics and Clinical Activity of NUC-1031, a Nucleotide Analogue, in Patients With Advanced Solid Tumours.
- ClinicalTrials.gov ID
- NCT01621854
- Acronym / sponsor ID
- ProGem1 / PRO-001
- Conditions
- Cancer
- Keywords
- cancer, nucleoside analogue, advanced solid tumours
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Nucana
- Study start
- Oct 2012
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 18 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 I. 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 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.
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. 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, until disease progression, for as long as the participant receives clinical benefit in the opinion of the CI, the occurrence of unmanageable drug related toxicity despite dose modification or if the study participant declines further treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NUC-1031 | Experimental | Drug: NUC-1031Cohort 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NUC-1031Cohort 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 |
Primary outcome
To determine the RP2D of NUC-1031 administered as either an I.V. weekly or twice-weekly schedule in patients with advanced solid tumours.
Time frame: 1.5 years
Adverse events (AE) and changes from baseline in vital signs, clinical laboratory parameters, and electrocardiography (ECG) assessments will be assessed
To further evaluate the safety profile of NUC-1031 in an expanded cohort at RP2D
Time frame: 1 year
Adverse events (AE) and changes from baseline in vital signs, clinical laboratory parameters, and electrocardiography (ECG) assessments
2 secondary outcomes
To determine the pharmacokinetics of NUC-1031 and its metabolites.
Time frame: 1.5 years
To explore the preliminary anti-tumour activity of NUC-1031 [given at the RP2D and preferred schedule selected from Part I]
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr Blagden, PhD FRCP principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NUC-1031 in people with Cancer, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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. (time frame: 1.5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2024.