NSCLCPhase 2NCT05651269
Milciclib in Combination With Gemcitabine in Advanced NSCLC
A Phase 2 study testing Milciclib Dose: 150 mg/day Mode of administration: oral in people with NSCLC, run by Tiziana Life Sciences LTD.
Trial summary
The goal of this interventional clinical study is to evaluate the safety and efficacy of Milciclib plus gemcitabine in the treatment of persons with advanced NSCLC. This is an open label uncontrolled clinical trial Eligible patients will receive 150 mg/day of milciclib orally using the 7 days on/7 days off schedule in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC
- What is being tested?
- Milciclib Dose: 150 mg/day Mode of administration: oral
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- No sites listed yet
- Study dates
- 15 Mar 2023to Jun 2025
- Phase
- Phase 2
- 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
- Histologically confirmed NSCLC with an associated G12A, G12D, G12F, G12R, G12S, G12V, or G13D KRAS mutation, or, any pathogenic KRAS mutation other than G12C, as determined by a Sponsor-approved laboratory
- Male or female patients at least 18 years of age
- Advanced unresectable recurrent or metastatic disease not amenable to local treatment with surgery or radiotherapy
- Documented disease progression after at least one line of prior SoC therapy
- Presence of measurable disease on computed tomography (CT) or magnetic resonance imaging (MRI) scan as defined by RECIST v1.1. A previously irradiated lesion may be considered a target lesion if clearly progressing
- Previous systemic anticancer treatment completed ≥ 3 weeks, major surgery ≥ 2 weeks, and radiation therapy ≥ 4 weeks prior to study enrollment
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- Any adverse effects from prior surgery, radiotherapy, or antineoplastic therapy must have improved to Grade 1 or less by the time of enrollment
- ECOG performance status 0-2 at the time of enrollment
- Life expectancy at least 12 weeks
- Adequate bone marrow function as evidenced by meeting all the following requirements:
- Absolute neutrophil count (ANC) ≥ 1500 cells/μL without the use of hematopoietic growth factors within the last 2 weeks before screening
- Platelet count 100,000 cells/μL without the use of platelet transfusion within the last 2 weeks before screening
- Hemoglobin ≥ 9 g/dL without the use of red blood cell (RBC) transfusion within the last 2 weeks before screening
- Adequate hepatic function as evidenced by meeting all the following requirements:
- Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), unless explicitly related to documented Gilbert's syndrome
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 3 × ULN; if liver metastases are present, then ≤ 5 × ULN is allowed
- Adequate renal function as evidenced by an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 of body surface area.
- Female patients of childbearing potential (FCBP) must present with a negative serum pregnancy test and must agree to employ adequate birth control measures for the duration of the study and until 3 months after the end of last dose of the study drug. Female patients who are lactating must agree to stop breastfeeding from the start of study treatment until 1 month after the end of treatment. Lack of childbearing potential is indicated by > 12 months without menses, or after surgical sterility, or as indicated by follicle-stimulating hormone (FSH) concentration.
- Male patients must be surgically sterile or agree to use a double-barrier contraception method or abstain from heterosexual activity with an FCBP starting at the first dose of treatment and until 3 months after the last dose of the study drug. Male patients must also agree to refrain from sperm donation, storage, or banking during these same time periods.
- Patient is willing and able to comply with the requirements of the study protocol.
Who cannot join
- Previous treatment with sotorasib or any experimental anti-KRAS targeted agent, and/or previous treatment with gemcitabine
- Documented KRAS G12C mutation and previously untreated with sotorasib
- Existing Grade 2 or higher retinal conditions (e.g., retinal tear, exudate, hemorrhage)
- Existing Grade 2 or higher neurological condition (tremor, ataxia, hypotension, confusion)
- Significant intercurrent illnesses and/or any of the following:
- Active uncontrolled peptic ulcer disease
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- Uncontrolled seizure disorders
- Active and uncontrolled CNS metastases (indicated by clinical symptoms, cerebral edema, corticosteroid and/or anticonvulsant requirement, or progressive disease); for controlled CNS metastases, patient should have been off corticosteroids for at least 14 days or on a tapering or stable dose of corticosteroids at a maximum dose of 12 mg/day prednisone-equivalent, without overt evidence of significant neurological deficits prior to enrollment
- Significant cardiac conduction abnormalities, including known familial prolonged QT syndrome, or screening QTcF > 480 msec
- Symptoms of congestive heart failure Grade 2 or higher
- Active, uncontrolled bacterial, fungal, or viral infection or an unexplained fever > 38.5°C which in the investigator's opinion might compromise the patient's participation in the study
- Known history of difficulty swallowing, malabsorption, or other conditions that may reduce absorption of the product
- Chronic Grade ≥ 2 diarrhea
- Presence or history of any other active malignancy within 2 years other than a history of adequately treated basal or squamous cell carcinoma of the skin, or any adequately treated in situ carcinoma
- Active known human immunodeficiency virus ( HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Active hepatitis B is defined as positive hepatitis B surface antigen (HBsAg) or immunoglobulin (Ig)M hepatitis B core antibody (anti-HBc) with or without positive HBV DNA. Active hepatitis C is defined as positive HCV RNA and/or anti-HCV antibody. HIV test according to local practice and local regulatory guidance
- Female patient who is pregnant or lactating at the time of enrollment
- Any other medical or social condition deemed by the investigator to be likely to interfere with a patient's ability to cooperate and participate in the study or interfere with the interpretation of the results.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Milciclib in Combination With Gemcitabine in Advanced Non-Small Cell Lung Cancer
The goal of this interventional clinical study is to evaluate the safety and efficacy of Milciclib plus gemcitabine in the treatment of persons with advanced NSCLC. This is an open label uncontrolled clinical trial
Eligible patients will receive 150 mg/day of milciclib orally using the 7 days on/7 days off schedule in combination with gemcitabine at the dose of 1000 mg/m² on Days 1, 8, and 15 every 4 weeks. Treatment cycles will be repeated every 4 weeks until progressive disease (radiologic or symptomatic deterioration), the start of a new systemic anticancer therapy, unacceptable toxicity, withdrawal per investigator's judgment, or withdrawal of consent, whichever occurs first.
Read the detailed description
This study is a multicenter, prospective, non-randomized, open-label, single-arm Phase 2 study in locally advanced non-resectable recurrent and/or metastatic KRAS-mutated NSCLC after failure of at least 1 line of SoC therapy.
All patients will be screened for KRAS mutation status. A total of up to 28 patients harboring G12A, G12D, G12F, G12R, G12S, G12V, or G13D KRAS mutations, or, any pathogenic KRAS mutation other than G12C mutations will be enrolled and treated. According to the Simon's 2-stage design, 13 patients will be treated at Stage 1 with up to 15 patients treated at Stage 2.
At the completion of Stage 1, a review of the tumor response evaluation will be undertaken to determine if the second stage should be conducted. If there are 2 or more patients with a complete response (CR) or partial response (PR) in the first 13 patients, an additional 15 patients will be accrued.
Stage 1 will be considered complete when all patients have experienced progressive disease (radiologic or symptomatic deterioration), started a new systemic anticancer therapy, have withdrawn per investigator's judgment or experienced unacceptable toxicity, have withdrawn consent, or have completed 6 cycles of treatment.
In addition, Stage 1 patients who, at the time of transition to Stage 2, were responding with a CR, PR, or stable disease, will be allowed to continue in the study at the recommended Phase 2 dose; or lower for safety reasons). These patients will not be part of the 15 new patients to be targeted in Stage 2, because they will have already received treatment with milciclib plus gemcitabine in Stage 1, but they will provide additional safety information regarding prolonged treatment with milciclib plus gemcitabine
- Conditions
- NSCLC
- Being tested
- Milciclib Dose: 150 mg/day Mode of administration: oral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Milciclib Dose: 150 mg/day Mode of administration: oralDrug
Also called Combination product: gemcitabine Dose: 1000 mg/m2 Mode of administration: intravenous
milciclib plus gemcitabine
| Study group | Role | What they receive |
|---|---|---|
| Milciclib plus gemcitabine | Experimental | Name: milciclib Dose: 150 mg/day Mode of administration: oral
Combination product:
Name: gemcitabine Dose: 1000 mg/m2 Mode of administration: intravenous Receives: Drug: Milciclib Dose: 150 mg/day Mode of administration: oral |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease progression
The primary endpoint is an independent, central reader-assessed, blinded to time of scan, and confirmed objective response rate (ORR), defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR), using RECIST v1.1. Any patient with CR or PR must be able to confirm the CR or PR at least 4 weeks following the first observation.
Measured: The study will be closed 6 months after the last scheduled visit
Secondary outcomes (2)
Duration of response
The secondary efficacy endpoints (using central reader-assessed response according to RECIST v1.1 when applicable) are:
- Duration of response (DoR), defined as the duration between first documentation of CR or PR to first documentation of disease progression or death
- Progression-free-survival (PFS), defined as the time from the date of first dose of study drug to the date of first documented disease progression or death due to any cause
- Time to response (TTR), defined as the time from first dose of study drug to first documentation of CR or PR
- Overall survival (OS), defined as the time from the date of first dose of study drug to the date of death due to any cause
Measured: time from date of randomization to date of death from any cause or end of study up to 12 months
Adverse Events
Incidence of AEs and SAEs
Measured: Up to 6 months after the last scheduled visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2022
- Study start15 Mar 2023 (estimated)
- Primary completionDec 2024 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tiziana Life Sciences LTD
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Matthew Davis, MD, Study chair, Tiziana Life Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05651269
- Sponsor's protocol ID
- TILS-020
- Status last verified
- Dec 2022
- First submitted
- 2 Dec 2022
- Last updated
- 15 Dec 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is no planned sharing of data
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Milciclib in Combination With Gemcitabine in Advanced Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT05651269
- Acronym / sponsor ID
- TILS-020
- Conditions
- NSCLC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- Tiziana Life Sciences LTDIndustry (pharma, biotech, devices)
- Study start
- 15 Mar 2023 (estimated)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 15 Dec 2022 (actual)
- 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.
The goal of this interventional clinical study is to evaluate the safety and efficacy of Milciclib plus gemcitabine in the treatment of persons with advanced NSCLC. This is an open label uncontrolled clinical trial
Eligible patients will receive 150 mg/day of milciclib orally using the 7 days on/7 days off schedule in combination with gemcitabine at the dose of 1000 mg/m² on Days 1, 8, and 15 every 4 weeks. Treatment cycles will be repeated every 4 weeks until progressive disease (radiologic or symptomatic deterioration), the start of a new systemic anticancer therapy, unacceptable toxicity, withdrawal per investigator's judgment, or withdrawal of consent, whichever occurs first.
Detailed description
This study is a multicenter, prospective, non-randomized, open-label, single-arm Phase 2 study in locally advanced non-resectable recurrent and/or metastatic KRAS-mutated NSCLC after failure of at least 1 line of SoC therapy.
All patients will be screened for KRAS mutation status. A total of up to 28 patients harboring G12A, G12D, G12F, G12R, G12S, G12V, or G13D KRAS mutations, or, any pathogenic KRAS mutation other than G12C mutations will be enrolled and treated. According to the Simon's 2-stage design, 13 patients will be treated at Stage 1 with up to 15 patients treated at Stage 2.
At the completion of Stage 1, a review of the tumor response evaluation will be undertaken to determine if the second stage should be conducted. If there are 2 or more patients with a complete response (CR) or partial response (PR) in the first 13 patients, an additional 15 patients will be accrued.
Stage 1 will be considered complete when all patients have experienced progressive disease (radiologic or symptomatic deterioration), started a new systemic anticancer therapy, have withdrawn per investigator's judgment or experienced unacceptable toxicity, have withdrawn consent, or have completed 6 cycles of treatment.
In addition, Stage 1 patients who, at the time of transition to Stage 2, were responding with a CR, PR, or stable disease, will be allowed to continue in the study at the recommended Phase 2 dose; or lower for safety reasons). These patients will not be part of the 15 new patients to be targeted in Stage 2, because they will have already received treatment with milciclib plus gemcitabine in Stage 1, but they will provide additional safety information regarding prolonged treatment with milciclib plus gemcitabine
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Milciclib plus gemcitabine | Experimental | Drug: Milciclib Dose: 150 mg/day Mode of administration: oralName: milciclib Dose: 150 mg/day Mode of administration: oral Combination product: Name: gemcitabine Dose: 1000 mg/m2 Mode of administration: intravenous |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologically confirmed NSCLC with an associated G12A, G12D, G12F, G12R, G12S, G12V, or G13D KRAS mutation, or, any pathogenic KRAS mutation other than G12C, as determined by a Sponsor-approved laboratory
- Male or female patients at least 18 years of age
- Advanced unresectable recurrent or metastatic disease not amenable to local treatment with surgery or radiotherapy
- Documented disease progression after at least one line of prior SoC therapy
- Presence of measurable disease on computed tomography (CT) or magnetic resonance imaging (MRI) scan as defined by RECIST v1.1. A previously irradiated lesion may be considered a target lesion if clearly progressing
Key exclusion criteria (17 listed)
- Previous treatment with sotorasib or any experimental anti-KRAS targeted agent, and/or previous treatment with gemcitabine
- Documented KRAS G12C mutation and previously untreated with sotorasib
- Existing Grade 2 or higher retinal conditions (e.g., retinal tear, exudate, hemorrhage)
- Existing Grade 2 or higher neurological condition (tremor, ataxia, hypotension, confusion)
- Significant intercurrent illnesses and/or any of the following:
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 |
|---|---|---|
| Milciclib Dose: 150 mg/day Mode of administration: oralAlso: Combination product: gemcitabine Dose: 1000 mg/m2 Mode of administration: intravenousmilciclib plus gemcitabine | Drug | Milciclib plus gemcitabine |
Primary outcome
Disease progression
Time frame: The study will be closed 6 months after the last scheduled visit
The primary endpoint is an independent, central reader-assessed, blinded to time of scan, and confirmed objective response rate (ORR), defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR), using RECIST v1.1. Any patient with CR or PR must be able to confirm the CR or PR at least 4 weeks following the first observation.
2 secondary outcomes
Duration of response
Time frame: time from date of randomization to date of death from any cause or end of study up to 12 months
Adverse Events
Time frame: Up to 6 months after the last scheduled visit
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2022.
- Individual participant dataSharing planned: No. There is no planned sharing of data
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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.
Matthew Davis, MD study chair
Tiziana Life Sciences
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Milciclib Dose: 150 mg/day Mode of administration: oral in people with NSCLC, run by Tiziana Life Sciences LTD.
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 20 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 15 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact John Andrews, PhD (910-232-8932, jandrews@TizianaLifeSciences.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease progression (time frame: The study will be closed 6 months after the last scheduled visit). 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 15 Dec 2022.