Comparing 4 approaches for advanced solid tumors
Official title: A Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of VVD-133214 as Monotherapy and in Combination in Participants With Advanced Solid Tumors
A Phase I, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-Tumor Activity of VVD-133214 as Monotherapy and in Combination in Participants With Advanced Solid Tumors Harboring Microsatellite Instability (MSI) and/or Deficient Mismatch Repair (dMMR)
- Phase 1
- 4 groups
- Sites in Vancouver and Toronto
- Recruiting
Interventions
- Medication
VVD-133214
VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.
- Medication
Pembrolizumab
Pembrolizumab will be administered by intravenous (IV) infusion at a fixed dose of 200 mg on Day 1 of each 21-day cycle.
- Medication
Bevacizumab
Bevacizumab will be administered by intravenous (IV) infusion at a fixed dose of 7.5 mg/kg on Day 1 of each 21-day cycle.
Canadian Sites (2)
1 of 2 recruiting
- Recruiting
Princess Margaret Cancer Center
Toronto, Ontario
- Completed
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia
Eligibility Criteria
See who this study is looking for31 criteria
The trial’s own eligibility text, word for word from the registry. Only the trial site can say who takes part.
Inclusion
- +Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- +Have received and then progressed following, or are intolerant to, standard therapy in the advanced setting
- +Presence of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- +Life expectancy of at least (≥)12 weeks
- +Availability of formaldehyde-fixed paraffin-embedded (FFPE) archival tumor tissue for submission to SponsorSponsorThe organisation responsible for the study overall.Read more →/central laboratory for retrospective central testing; for participants without archival tissue, a biopsy from either primary or metastatic tumor lesion, deemed medically feasible, must be taken
- +Adequate hematologic, end-organ, and cardiovascular function, as defined in the protocolProtocolThe detailed plan a study must follow.Read more →
- +Have a microsatellite instability (MSI) and/or deficient mismatch repair (dMMR), histologically or cytologically documented advanced (unresectable and/or metastatic) solid tumor; For the combination with bevacizumab only: advanced, or metastatic colorectal adenocarcinoma (CRC) treated with at least 2 but no more than 3 prior lines of systemic therapy for the treatment of advanced CRC; For the combination with pembrolizumab only: Histologically confirmed locally advanced, or metastatic CRC with no prior systemic treatment for metastatic disease and not amenable to surgery
Exclusion
- −Known hypersensitivity or intolerance to ingredients from the study drug formulation including patients with rare genetic disorders such as galactosaemia, glucose-galactose intolerance or congenital lactase deficiency
- −Has a positive test at screeningScreeningThe checks done before joining, to see whether a study fits.Read more → for hepatitis B virus, hepatitis C virus, or for human immodeficiency virus (HIV), per local diagnostic standard and in accordance with local laws and regulations
- −Inability or unwillingness to swallow pills
- −Malabsorption syndrome or other condition that would interfere with enteral absorption
- −Known uncontrolled central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic controlControl groupThe group a new treatment is measured against.Read more →) and/or carcinomatous meningitis
- −Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but not limited to tuberculosis and atypical mycobacterial disease), parasitic, or other infection (excluding fungal infections of nail beds), or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 2 weeks prior to the start of drug administration (related to the completion of the course of antibiotics, except if for tumor fever) or 6 months for any intracranial abscess
- −Uncontrolled diabetes or symptomatic hyperglycemia (i.e., well controlled defined as a screening hemoglobin A1c \<8% and no urinary ketoacidosis)
- −Significant cardiovascular/cerebrovascular disease within 6 months prior to Day 1 of study drug administration
- −Alcohol or drug dependence or abuse
- −Patients with known Werner (WRN) syndrome
- −Prior treatment with any WRN helicase inhibitor
- −Treatment with moderate or strong CYP3A4 inducers within 14 days prior to initiation of study treatment
- −Treatment with moderate or strong CYP3A4 or P-glycoprotein inhibitors within 14 days prior to initiation of study treatment
- −Additional Exclusion CriteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → for the Combination with Bevacizumab Only:
- −Deep venous thrombosis (DVT) or pulmonary embolism (PE) within 12 weeks prior to study drug administration
- −Known coagulopathy that increases the risk of bleeding
- −Patients with Grade 2+ proteinuria (exception: if 24-hour urinary protein is less than 1.0 gm/24 hours)
- −Additional Exclusion Criteria for the Combination with Pembrolizumab Only:
- −Active or history of autoimmune disease or immune deficiency with some exceptions
- −History of interstitial lung disease or pneumonitis
- −Treatment with systemic immunosuppressive medication (such as corticosteroids) within 2 weeks prior to initiation of study treatment with some exceptions
- −Treatment with organ transplant/graft tissue
- −Pregnancy, breastfeeding, or intention of becoming pregnant during the study
- −Had major surgery within 4 weeks prior to study drug administration
In plain language
Assembled directly from this trial’s registry record. Every sentence traces to a field below — nothing here is generated or interpreted.
What this study is
This study is testing a treatment for a condition.
Phase 1Phase 1The earliest stage of human testing, in a small group, focused on safety.Read more → — an early safety study in a small group, checking how it is tolerated and at what dose.
From the trial registry
Built from these fields:
- designModule.designInfo.primaryPurpose
- designModule.phases
Who receives what
There are 4 groups in this study.
Groups A and B receive VVD-133214.
Registry label: A: VVD-133214 Dose Escalation · B: VVD-133214 Monotherapy Expansion
Group C receives VVD-133214 and Pembrolizumab.
Registry label: C: VVD-133214 + Pembrolizumab Expansion
Group D receives VVD-133214 and Bevacizumab.
Registry label: D: VVD-133214 + Bevacizumab Expansion
From the trial registry
Built from these fields:
- armsInterventionsModule.armGroups[].label
- armsInterventionsModule.armGroups[].type
- armsInterventionsModule.armGroups[].interventionNames
How the study is run
Groups are assigned by the study team using set rules, rather than by chance.
This study is open-labelOpen-labelEveryone knows which treatment is being given — nothing is hidden.Read more →: everyone knows which treatment is being given, including you and the study team.
From the trial registry
Built from these fields:
- designModule.designInfo.allocation
- designModule.designInfo.maskingInfo.masking
Is there a placebo?
This study does not list a placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → group.
From the trial registry
Built from these fields:
- armsInterventionsModule.armGroups[].type
- armsInterventionsModule.armGroups[].interventionNames
Who the study is looking for
The study lists a minimum age of 18 years, with no upper limit given.
The study is open to people of any sex.
The study does not accept healthy volunteersHealthy volunteerSomeone without the condition being studied who takes part anyway.Read more →.
These are the criteria the study lists. Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can decide whether someone can take part.
From the trial registry
Built from these fields:
- eligibilityModule.minimumAge
- eligibilityModule.sex
- eligibilityModule.healthyVolunteers
How big and how long
The study aims to enrol about 280 people.
The study is currently expected to finish around May 2027.
The main measurement is taken over: From first dose of study drug(s) until 30 days after the final dose of VVD-133214 or 90 days after last dose of bevacizumab or pembrolizumab.
From the trial registry
Built from these fields:
- designModule.enrollmentInfo.count
- statusModule.completionDateStruct.date
- outcomesModule.primaryOutcomes[].timeFrame
What the study measures
Incidence of Adverse EventsAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more →, with Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0) — measured over From first dose of study drug(s) until 30 days after the final dose of VVD-133214 or 90 days after last dose of bevacizumab or pembrolizumab.
Incidence of Dose-Limiting Toxicities — measured over Cycle 1 (1 cycle is 3 weeks).
From the trial registry
Built from these fields:
- outcomesModule.primaryOutcomes[].measure
- outcomesModule.primaryOutcomes[].timeFrame
Source: NCT06004245 on ClinicalTrials.gov. The full registry text is further down this page — this summary never replaces it.
Not medical advice. What do these terms mean?
What is being tested — in plain terms
About VVD-133214Drug
VVD-133214 will be administered orally and once daily (QD) in 3-week cycles.
From the trial registry — its own words, unedited.
What a drug is here: A medicine — a chemical or small-molecule treatment — given as the thing being studied.
Read the full explanation → · in clinical review
About PembrolizumabDrug
Pembrolizumab will be administered by intravenous (IV) infusion at a fixed dose of 200 mg on Day 1 of each 21-day cycle.
From the trial registry — its own words, unedited.
What a drug is here: A medicine — a chemical or small-molecule treatment — given as the thing being studied.
Read the full explanation → · in clinical review
About BevacizumabDrug
Bevacizumab will be administered by intravenous (IV) infusion at a fixed dose of 7.5 mg/kg on Day 1 of each 21-day cycle.
From the trial registry — its own words, unedited.
What a drug is here: A medicine — a chemical or small-molecule treatment — given as the thing being studied.
Read the full explanation → · in clinical review
Common questions
Answered from this trial’s registry record. Where the record doesn’t say, these answers say so rather than filling the gap.
Am I eligible for this trial?
Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can decide whether someone can take part. Concord cannot make that determination, and neither can any tool that has not examined you.
What the study lists: a minimum age of 18 years.
The full inclusionInclusion criteriaThe things you must have or be for a study to consider you.Read more → and exclusion criteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → are published on this page, exactly as the study team wrote them.
The useful next step is to bring this trial to your doctor. Answering a few questions first gives them something concrete to review.
From the trial registry
- eligibilityModule.minimumAge
- eligibilityModule.eligibilityCriteria
Is there a placebo?
This study does not list a placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → group.
From the trial registry
- armsInterventionsModule.armGroups[].type
Would I know which treatment I am getting?
This study is open-labelOpen-labelEveryone knows which treatment is being given — nothing is hidden.Read more →: everyone knows which treatment is being given, including you and the study team.
Groups are assigned by the study team using set rules, rather than by chance.
From the trial registry
- designModule.designInfo.maskingInfo.masking
- designModule.designInfo.allocation
Who can join?
The study lists a minimum age of 18 years, with no upper limit given.
It is open to people of any sex.
It does not accept healthy volunteersHealthy volunteerSomeone without the condition being studied who takes part anyway.Read more →.
Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can confirm whether a particular person can take part.
From the trial registry
- eligibilityModule.minimumAge
- eligibilityModule.sex
- eligibilityModule.healthyVolunteers
How long would this take?
The study's main measurement is taken over: From first dose of study drug(s) until 30 days after the final dose of VVD-133214 or 90 days after last dose of bevacizumab or pembrolizumab.
The study as a whole is currently expected to finish around 2027-05-31.
How long any one person takes part can differ from the study length. The study team can tell you what the schedule looks like in practice.
From the trial registry
- outcomesModule.primaryOutcomes[].timeFrame
- statusModule.completionDateStruct.date
How many people are taking part?
The study aims to enrol about 280 people.
From the trial registry
- designModule.enrollmentInfo.count
Where is this happening?
This study lists 4 locations, including: Vancouver, British Columbia, Canada; Toronto, Ontario, Canada; Ann Arbor, Michigan, United States; Grand Rapids, Michigan, United States.
Sites can open and close during a study, so confirm with the team before travelling.
From the trial registry
- trial_locations
About This Trial
This is a first-in-human, Phase I, open-label, multicenter, dose-escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of VVD-133214 monotherapy, and in combination with bevacizumab or pembrolizumab, in participants with microsatellite instability (MSI) and/or deficient mismatch repair (dMMR) advanced solid tumors. VVD-133214 is an oral drug that acts on a protein called Werner (WRN), which may promote the growth of cancers that are MSI and/or dMMR. By acting on WRN, VVD-133214 may be able to block the growth of these types of cancer.
Other Sites (2)
University of Michigan
Ann Arbor, Michigan, United States
START Midwest
Grand Rapids, Michigan, United States
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See if this trial could fit youThis page is for informational purposes only and does not constitute medical advice. Clinical trial eligibility can only be determined by the trial site after proper screening. Trial information is sourced from ClinicalTrials.gov and may not reflect the most current status. Always consult your healthcare provider before making decisions about clinical trial participation.