Advanced Pancreatic CancerPhase 1NCT03889795
Phase IB Metformin, Digoxin, Simvastatin in Solid Tumors
A Phase 1 study testing Metformin, Simvastatin and Digoxin in people with Advanced Pancreatic Cancer and Advanced Solid Tumor, run by Danae Hamouda, MD at 1 site in United States.
Trial summary
This is a single-center trial in subjects with pancreatic cancer and other advanced solid tumors. It is an open-label, single arm dose escalation Phase IB trial with subjects accrued in a 3 subject dose escalation cohort. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Pancreatic Cancer, Advanced Solid Tumor
- What is being tested?
- Metformin, Simvastatin and Digoxin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jun 2019to 30 Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Subject ≥18 years with histologically confirmed solid tumor.
- Dose expansion subjects must have at least one tumor mass amenable to core needle biopsy.
- Refractory or intolerant to established standard of care.
- Have at least one tumor mass amenable to core needle biopsy. Adequate Archival Tissue required for patients that will take part in the dose escalation cohorts.
- ECOG performance status (PS) = 0-2, or Karnofsky PS ≥60%, or Lansky PS ≥60%.
- Normal organ and marrow function: absolute granulocyte count ≥1,000/mm3, absolute lymphocyte count ≥400/mm3, platelets ≥100,000/mm3, total bilirubin ≤ institutional upper normal limit, AST/ASL ≤2x institutional upper limit of normal, GFR >60 mL/min/1.73 m2 and creatinine <1.5 mg/dL.
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- Subject has recovered to CTCAE Grade 1 or better from all adverse events associated with prior therapy or surgery. Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to CTCAE Grade 2 or better.
- If female of childbearing potential, has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a negative serum test will then be required for study entry.
- Ability to understand and the willingness to sign a written informed protocol specific consent.
Who cannot join
- Anti-cancer chemotherapy, biologic therapy or immunotherapy within 3 weeks or radiation therapy within 2 weeks of first infusion.
- Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.
- Patients with only PET non-avid disease.
- Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.
- Known history of rhabdomyolysis.
- History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the Investigator.
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- Known HIV or chronic Hepatitis B or C infection.
- Have signs and symptoms consistent with an active infection.
- Live vaccination for the prevention of infectious disease administered <30 days prior to the start of study therapy or inactivated vaccination <14 days prior to the start of study therapy.
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to Metformin, Simvastatin, and/or Digoxin.
- Patients diagnosed with Wolff-Parkinson-White Syndrome or electrocardiographic (ECG) pattern. Other cardiac conditions including: Previous MI with evidence of residual electrographic pattern consisted with bradycardia/heart block. Atrio-ventricular (AV) heart block (currently ongoing). History of ventricular fibrillation. Sick Sinus Syndrome or Sinus bradycardia thought to be caused by sinus node disease, unless effectively treated. Heart failure associated with preserved left ventricular ejection fraction, including constructive pericarditis, restrictive cardiomyopathy, and Amyloid heart muscle disease.
- Women of childbearing potential who are found to be pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) or nursing.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Toledo, Eleanor N. Dana Cancer Center
Toledo, Ohio, 43614
About this study
Official title: Phase IB Trial of Metformin, Digoxin, Simvastatin in Subjects With Advanced Pancreatic Cancer and Other Advanced Solid Tumors
This is a single-center trial in subjects with pancreatic cancer and other advanced solid tumors. It is an open-label, single arm dose escalation Phase IB trial with subjects accrued in a 3 subject dose escalation cohort. Subjects with treated advanced solid tumors, and showing disease progression on established standard therapy, will be enrolled in this trial.
Read the detailed description
This is a single-center trial in subjects with pancreatic cancer and other advanced solid tumors. It is an open-label, single arm dose escalation Phase IB trial with subjects accrued in a 3 subject dose escalation cohort. Subjects with treated advanced solid tumors, and showing disease progression on established standard therapy, will be enrolled in this trial.
C3 (Simvastatin + Digoxin + Metformin) will be given as three oral pills within recommended package insert safe levels. Subjects will be accrued in 3-subject dose escalation cohorts. 3 additional subjects will be treated at the presumptive maximum effective cohort dose/schedule for a total of 6 subjects at maximum effective level.
- Conditions
- Advanced Pancreatic Cancer, Advanced Solid Tumor
- Being tested
- Metformin, Simvastatin, Digoxin
- Keywords
- Pancreatic, Solid Tumor, Advanced Pancreatic Cancer, Dose Escalation, Maximum Tolerated Dose
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage
Metformin oral pill will be taken daily at breakfast (cohort 1) and breakfast and dinner (cohort 2 and 3).
SimvastatinDrug
Also called Zocor
Simvastatin oral pill will be taken daily in the evening.
DigoxinDrug
Also called Digitalis
Digoxin oral pill will be taken once daily.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | C3 (Metformin, Simvastatin and Digoxin) will be dosed each day of a 28 calendar day cycle. The starting dose level will be increased with each cohort. There are 3 cohorts. Upon reaching maximum tolerated dose, an expansion cohort will be opened. Cohort 1 - Metformin 850mg po/day, Simvastatin 5mg po/day, Digoxin 0.0625 mg po/day. Cohort 2 - Metformin 850 mg po/day for two weeks and 1,700 mg po/day for next two weeks, Simvastatin 20 mg po/day, Digoxin 0.25 mg po/day. Cohort 3 - Metformin 850 mg po/day for two weeks and 1,700 mg po/day for next two weeks, Simvastatin 40 mg po/day, Digoxin 0.25 mg po/day for two weeks, 0.375 mg po/day for the next two weeks for cycle 1. Subjects will receive 0.50 mg po/day in Cohort 3, Cycle 2 and beyond. Metformin to be taken at Breakfast and Dinner time (as applicable), Simvastatin at Bed time and Digoxin once daily. Receives: Drug: Metformin; Drug: Simvastatin; Drug: Digoxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose and/or Recommended Dose within the tested C3 dose range
Occurrence of any ≥ Grade 3 toxicity encountered within the four weeks following the administration of C3, regardless of attribution
Measured: Up to one year
Secondary outcomes (4)
Safety and Tolerability: Occurrence of treatment - emergent adverse events (TEAEs) and other abnormalities
Occurrence of treatment - emergent adverse events (TEAEs) and occurrence of abnormalities in laboratory test values, markedly abnormal vital sign measurements, and clinically significant abnormal electrocardiograms (ECGs), including conduction abnormalities and changes in QT interval
Measured: Up to 2 years
Efficacy (Disease Response)
Response and progression evaluated using Response Evaluation criteria in solid tumors
Measured: Up to 2 years
Assess BIRC5 levels of expression in tumor tissue
Blood samples for pharmacokinetic analysis of C3 will be collected at designated time points.
Measured: RNA and protein levels of expression at baseline and at 2 months after C3 treatment
Assess molecular changes induced by C3 administration in the blood for biomarker sensitivity/resistance assessment
Molecular signal tumor blood (plasma) and microenvironment protein expression patterns via quantitative mass spectrometry.
Measured: Baseline and at 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2019
- Study start5 Jun 2019
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Pancreatic CancerStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- 3 Subjects per Cohort + 3 additional subjects in Expansion Cohort.
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Danae Hamouda, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Danae Hamouda, MD, University of Toledo
- Investigators
- Danae Hamouda, MD, Principal investigator, University of Toledo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03889795
- Sponsor's protocol ID
- C3
- Status last verified
- Oct 2025
- First submitted
- 19 Mar 2019
- Last updated
- 20 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IB Trial of Metformin, Digoxin, Simvastatin in Subjects With Advanced Pancreatic Cancer and Other Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03889795
- Acronym / sponsor ID
- C3
- Conditions
- Advanced Pancreatic Cancer, Advanced Solid Tumor
- Keywords
- Pancreatic, Solid Tumor, Advanced Pancreatic Cancer, Dose Escalation, Maximum Tolerated Dose
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Danae Hamouda, MDUniversity, hospital or other
- Study start
- 5 Jun 2019 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 26 Mar 2019 (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.
This is a single-center trial in subjects with pancreatic cancer and other advanced solid tumors. It is an open-label, single arm dose escalation Phase IB trial with subjects accrued in a 3 subject dose escalation cohort. Subjects with treated advanced solid tumors, and showing disease progression on established standard therapy, will be enrolled in this trial.
Detailed description
This is a single-center trial in subjects with pancreatic cancer and other advanced solid tumors. It is an open-label, single arm dose escalation Phase IB trial with subjects accrued in a 3 subject dose escalation cohort. Subjects with treated advanced solid tumors, and showing disease progression on established standard therapy, will be enrolled in this trial.
C3 (Simvastatin + Digoxin + Metformin) will be given as three oral pills within recommended package insert safe levels. Subjects will be accrued in 3-subject dose escalation cohorts. 3 additional subjects will be treated at the presumptive maximum effective cohort dose/schedule for a total of 6 subjects at maximum effective level.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 3 Subjects per Cohort + 3 additional subjects in Expansion Cohort.
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Drug: Metformin, Drug: Simvastatin, Drug: DigoxinC3 (Metformin, Simvastatin and Digoxin) will be dosed each day of a 28 calendar day cycle. The starting dose level will be increased with each cohort. There are 3 cohorts. Upon reaching maximum tolerated dose, an expansion cohort will be opened. Cohort 1 - Metformin 850mg po/day, Simvastatin 5mg po/day, Digoxin 0.0625 mg po/day. Cohort 2 - Metformin 850 mg po/day for two weeks and 1,700 mg po/day for next two weeks, Simvastatin 20 mg po/day, Digoxin 0.25 mg po/day. Cohort 3 - Metformin 850 mg po/day for two weeks and 1,700 mg po/day for next two weeks, Simvastatin 40 mg po/day, Digoxin 0.25 mg po/day for two weeks, 0.375 mg po/day for the next two weeks for cycle 1. Subjects will receive 0.50 mg po/day in Cohort 3, Cycle 2 and beyond. Metformin to be taken at Breakfast and Dinner time (as applicable), Simvastatin at Bed time and Digoxin once daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subject ≥18 years with histologically confirmed solid tumor.
- Dose expansion subjects must have at least one tumor mass amenable to core needle biopsy.
- Refractory or intolerant to established standard of care.
- Have at least one tumor mass amenable to core needle biopsy. Adequate Archival Tissue required for patients that will take part in the dose escalation cohorts.
- ECOG performance status (PS) = 0-2, or Karnofsky PS ≥60%, or Lansky PS ≥60%.
Key exclusion criteria (12 listed)
- Anti-cancer chemotherapy, biologic therapy or immunotherapy within 3 weeks or radiation therapy within 2 weeks of first infusion.
- Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.
- Patients with only PET non-avid disease.
- Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.
- Known history of rhabdomyolysis.
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 |
|---|---|---|
| MetforminAlso: GlucophageMetformin oral pill will be taken daily at breakfast (cohort 1) and breakfast and dinner (cohort 2 and 3). | Drug | Dose Escalation |
| SimvastatinAlso: ZocorSimvastatin oral pill will be taken daily in the evening. | Drug | Dose Escalation |
| DigoxinAlso: DigitalisDigoxin oral pill will be taken once daily. | Drug | Dose Escalation |
Primary outcome
Maximum Tolerated Dose and/or Recommended Dose within the tested C3 dose range
Time frame: Up to one year
Occurrence of any ≥ Grade 3 toxicity encountered within the four weeks following the administration of C3, regardless of attribution
4 secondary outcomes
Safety and Tolerability: Occurrence of treatment - emergent adverse events (TEAEs) and other abnormalities
Time frame: Up to 2 years
Efficacy (Disease Response)
Time frame: Up to 2 years
Assess BIRC5 levels of expression in tumor tissue
Time frame: RNA and protein levels of expression at baseline and at 2 months after C3 treatment
Assess molecular changes induced by C3 administration in the blood for biomarker sensitivity/resistance assessment
Time frame: Baseline and at 2 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2025.
- Individual participant dataSharing planned: No
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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.
Danae Hamouda, MD principal investigator
University of Toledo
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 Metformin, Simvastatin and Digoxin in people with Advanced Pancreatic Cancer and Advanced Solid Tumor, run by Danae Hamouda, MD at 1 site in United States.
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 9 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 20 Oct 2025. 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 States. 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?
This study is still under way. Results are not available in the source record yet.
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?
Maximum Tolerated Dose and/or Recommended Dose within the tested C3 dose range (time frame: Up to one year). 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 Oct 2025.