Metastatic Pancreatic Ductal AdenocarcinomaPhase 1/2SLC-0111-17-01NCT03450018
A Study of SLC-0111 and Gemcitabine for Metastatic Pancreatic Ductal Cancer in Subjects Positive for CAIX
A Phase 1/2 study testing SLC-0111 and Gemcitabine Injection in people with Metastatic Pancreatic Ductal Adenocarcinoma, run by British Columbia Cancer Agency at 2 sites in Canada.
Trial summary
This is a multi-center, open-label Phase 1b study of SLC-0111 (oral) in combination with IV gemcitabine in CA IX positive subjects with mPDAC and comprises of 2 parts: Part 1: Dose Escalation Part 2: Dose Expansion Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Pancreatic Ductal Adenocarcinoma
- What is being tested?
- SLC-0111 and Gemcitabine Injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesCanada
- Study dates
- 10 Jan 2019to 16 May 2024
- Phase
- Phase 1/2
- 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
None listed.
Who cannot join
- Subjects negative for CAIX via IHC (biopsy or archival tissue)
- Previous treatment with any known CAIX Inhibitor
- Females who are pregnant, planning to become pregnant or breastfeeding.
- Severe cardiac disease which has required hospitalization within the past 3 months or which functionally limits a patient.
- Severe respiratory illness requiring supplemental oxygen or that significantly impacts functional status in daily life.
- Untreated CNS metastasis or CNS metastasis that has not been clinically stable for 28 days.
Show all 17Show fewer
- History of myocardial infarction, unstable angina, congestive heart failure (New York Heart Association class ≥ III/IV), cerebrovascular accident, transient ischaemic attack, limb claudication at rest in the 6 months prior to enrolment, or ongoing symptomatic dysrhythmias, or uncontrolled atrial or ventricular arrhythmias, or uncontrolled hypertension.
- Any condition or illness that, in the opinion of the Investigator would compromise subject safety or interfere with the evaluation of the safety of the investigational products.
- Subjects with documented cases of human immunodeficiency virus (HIV) and viral load detectable.
- Hypersensitivity to investigational products or their excipients or severe allergy to sulfonamides.
- Refractory nausea and vomiting, chronic gastrointestinal diseases, gastrointestinal bleeding, ulceration, or perforation within 12 weeks prior to the first administration of investigational products or significant bowel resection that would preclude adequate absorption.
- Known acute hepatitis B infection or chronic hepatitis B not currently on suppressive therapy.
- Known hepatitis C antibody positive and RNA positive. Subjects with hepatitis C antibody positivity but RNA negativity may enroll after consultation with hepatology.
- Active uncontrolled bacterial, viral, or fungal infections.
- Malignancy within the preceding 5 years (Subjects may be included in the trial if malignancy was a non-melanoma skin cancer, ductal carcinoma in-situ, early cervical malignancy, or at the discretion of the primary investigator if the malignancy has had curative intent treatment and has a < 10% chance of recurring within 5 years as per a well-recognized risk stratification tool specific for that malignancy.)
- Additional Dose Expansion Exclusion Criteria:
- Subjects cannot be enrolled in the dose expansion if they were enrolled during the dose escalation of the current study.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
BC Cancer - Vancouver
Vancouver, British Columbia, V5Z 4E6
About this study
Official title: An Open-label, Multi-center, Phase 1b Study to Investigate the Safety and Tolerability of SLC-0111 (WBI-5111) in Combination With Gemcitabine in Metastatic Pancreatic Ductal Adenocarcinoma Subjects Positive for Carbonic Anhydrase IX
This is a multi-center, open-label Phase 1b study of SLC-0111 (oral) in combination with IV gemcitabine in CA IX positive subjects with mPDAC and comprises of 2 parts:
- Part 1: Dose Escalation
- Part 2: Dose Expansion
Read the detailed description
This is a multi-center, open-label Phase 1b study of SLC-0111 (oral) in combination with IV gemcitabine in CA IX positive subjects with mPDAC and comprises of 2 parts:
- Part 1: Dose Escalation
- Part 2: Dose Expansion
Biopsy or archival tissue will be collected and tested for the presence of CAIX via Immunohistochemistry (IHC) and only subjects positive for CAIX will be enrolled in the dose-escalation and dose-expansion parts. Part 2 can only begin after a dosing regimen has been characterized in Part 1. Subjects who participated in Part 1 of study will not be eligible to participate in Part 2.
The dose escalation will aim to identify the safety, tolerability and MTD of the oral formulation of SLC-0111 in combination with IV gemcitabine. Additional subjects may be enrolled at the MTD in dose expansion cohort. Data collected will allow evaluation of safety, tolerability, PK, Pharmacodynamics (PD) and tumour response of SLC-0111 in combination with gemcitabine.
A traditional 3 + 3 dose escalation design will be utilized for this study. Cohorts (same dose level) of 3 to 6 evaluable subjects will participate in a dose escalation scheme in which the dose of SLC-0111 will be increased in each consecutive cohort. Dose escalation to a new cohort of subjects will occur after review of available Cycle 1 data. The dose of SLC-0111 will be escalated based on Table 1 and Table 2 in the protocol. Based on emerging data alternative dosing schedules, or dose reductions may be considered. Gemcitabine will be administered at the standard dose (1000 mg/m^2) and schedule (day 1, 8, and 15 of each cycle) but dose reductions may be considered if necessary.
- Each cohort will initially consist of up to 3 subjects.
- If none of the first 3 subjects in a cohort demonstrates dose limiting toxicities (DLTs), then the cohort will be declared safe and the next cohort will be opened for enrollment
- If 1 of the first 3 subjects in a cohort demonstrates DLTs, then 3 additional subjects will be accrued to that cohort for a total of 6 subjects
- If 1 out of 6 subjects in a cohort demonstrates DLTs, then the cohort will be declared safe and the next cohort (n=3)will be opened for enrollment
- If 2 or more subjects in a cohort demonstrates DLTs, that cohort will be declared to exceed the MTD
Following the identification of a Cohort that exceeds the MTD, the next lowest dose, or an intermediate dose level may be further explored.
The MTD will be defined as the highest dose level at which no more than 1 of 6 subjects demonstrates DLTs.
Intra-subject dose escalation will not be allowed in this study.
- Being tested
- SLC-0111, Gemcitabine Injection
- Keywords
- Gemcitabine, SLC-0111, PDAC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SLC-0111Drug
Also called WBI-5111
Oral SLC-0111
Gemcitabine InjectionDrug
Also called Gemcitabine
1000 mg/m^2 IV
| Study group | Role | What they receive |
|---|---|---|
| SLC-0111 + Gemcitabine | Experimental | Dose Level 1 - SLC-0111 (500 mg/day PO daily for 28 days) and Gemcitabine (1000 mg/m^2 IV on day 1, 8, and 15)
Dose Level 2 - SLC-0111 (750 mg/day PO daily for 28 days) and Gemcitabine (1000 mg/m^2 IV on day 1, 8, and 15)
Dose Level 3 - SLC-0111 (1000 mg/day PO daily for 28 days) and Gemcitabine (1000 mg/m^2 IV on day 1, 8, and 15) Receives: Drug: SLC-0111; Drug: Gemcitabine Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Adverse events (AEs) as assessed by CTCAE v5.0 will be determined by changes in safety assessments, including laboratory parameters, vital signs, ECG and physical examinations.
Measured: Up to Safety Follow-Up Visit (30 days +/- 7 days after permanently stopping study treatment)
Secondary outcomes (13)
The maximum tolerated dose [MTD] of SLC-0111 in combination with gemcitabine
Dose limiting toxicities (adverse events) will be determined by changes in safety assessments, including vital signs, clinical laboratory evaluations and ECG.
Measured: Up to Safety Follow-Up Visit (30 days +/- 7 days after permanently stopping study treatment)
Maximum Plasma Concentration [Cmax]
Analyze the pharmacokinetic profile of SLC-0111 and gemcitabine when used in combination by measuring the maximum (peak) plasma concentration (Cmax).
Measured: Up to 4 years
Time to Reach Maximum Plasma Concentraiton [Tmax]
Analyze the pharmacokinetic profile of SLC-0111 and gemcitabine when used in combination by the time to reach maximum (peak) plasma concentration following drug administration (Tmax).
Measured: Up to 4 years
Elimination Rate Constant from the Central Compartment [Kel]
Analyze the pharmacokinetic profile of SLC-0111 and gemcitabine when used in combination by measuring the elimination rate constant from the central compartment (Kel).
Measured: Up to 4 years
Volume of Distribution During Terminal Phase after Intravenous Administration [Vz]
Analyze the pharmacokinetic profile of SLC-0111 and gemcitabine when used in combination by measuring the volume of distribution during terminal phase after intravenous administration (Vz).
Measured: Up to 4 years
Area Under the Concentration-Time Curve from Zero up to a Definite Time T [AUC(0-T)]
Analyze the pharmacokinetic profile of SLC-0111 and gemcitabine when used in combination by measuring the area under the concentration-time curve from zero up to a definite time T (AUC(0-T)).
Measured: Up to 4 years
Area Under the Concentration-Time Curve from Zero up to Infinity [AUC(0-inf)]
Analyze the pharmacokinetic profile of SLC-0111 and gemcitabine when used in combination by measuring the area under the concentration-time curve from zero up to infinity with extrapolation of the terminal phase (AUC(0-inf)).
Measured: Up to 4 years
Elimination Half-Life
Analyze the pharmacokinetic profile of SLC-0111 and gemcitabine when used in combination by measuring the elimination half-life (T1/2).
Measured: Up to 4 years
Determine the Recommended Phase II Dose of SLC-0111 in combination with gemcitabine
Recommended Phase II Dose (RP2D) Safety and PK
Measured: Up to 2 years
Objective Response Rate [ORR] as Assessed by RECIST 1.1
Objective response rate (ORR) as assessed by RECIST 1.1 or clinical examination, where appropriate. ORR is the change in tumour volume from baseline to best overall response.
Measured: Up to 1 year
Progression-Free Survival [PFS] as Assessed by RECIST 1.1
Progression-free survival (PFS) as assessed by RECIST 1.1 or clinical examination, where appropriate. PFS is defined as the duration of time from start of treatment to progression or death, whichever occurs first. Subjects alive at the time of last follow up without disease progression will be censored at that time point.
Measured: Up to 1 year
Duration of Response as Assessed by RECIST 1.1
Duration of response as assessed by RECIST 1.1 or clinical examination, where appropriate. Duration of response is defined as the time from start of response [Complete Response (CR) or Partial Response (PR)] until progression or death due to any cause.
Measured: Up to 2 years
Overall Survival [OS]
Overall survival (OS) is defined as the time from initiation of investigational product(s) to death due to any cause.
Measured: Up to the end of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2018
- Study start10 Jan 2019
- Primary completion16 May 2024
- Study completion16 May 2024
Why it stopped: Changing treatment landscape: The availability of nab-paclitaxel with gemcitabine in the second-line setting has changed the feasibility of further recruitment and potential long-term development opportunities of SLC-0111 with gemcitabine alone.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (27)Papers the sponsor has linked to this study.
- Other trials for Metastatic Pancreatic Ductal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by British Columbia Cancer AgencyThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a traditional Phase I "3+3" study designed to identify the MTD by assessment of DLT of SLC-0111. Sample size estimates are not statistically based, but are based on acquisition of appropriate numbers of subjects to adequately describe the safety, tolerability, PK, and PD of SLC-0111 in combination with gemcitabine. Up to 18 subjects are anticipated to be enrolled in the dose escalation part; however, the actual number recruited will be dependent upon the number of dose escalations. Dose expansion (Part 2) may enroll up to 12 subjects.
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- British Columbia Cancer Agency
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Cancer Society (CCS), SignalChem Lifesciences Corporation
- Responsible party
- Sponsor
- Investigators
- Daniel J Renouf, MD, Principal investigator, BC Cancer - Vancouver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03450018
- Sponsor's protocol ID
- H17-02841
- Acronym
- SLC-0111-17-01
- Status last verified
- May 2024
- First submitted
- 13 Feb 2018
- Last updated
- 24 May 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Assaf E, Verlinde-Carvalho M, Delbaldo C, Grenier J, Sellam Z, Pouessel D, Bouaita L, Baumgaertner I, Sobhani I, Tayar C, Paul M, Culine S. 5-fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma. Oncology. 2011;80(5-6):301-6. doi: 10.1159/000329803. Epub 2011 Jul 18.
PubMed 21778770Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. doi: 10.1200/JCO.1997.15.6.2403.
PubMed 9196156Chang Q, Jurisica I, Do T, Hedley DW. Hypoxia predicts aggressive growth and spontaneous metastasis formation from orthotopically grown primary xenografts of human pancreatic cancer. Cancer Res. 2011 Apr 15;71(8):3110-20. doi: 10.1158/0008-5472.CAN-10-4049. Epub 2011 Feb 22.
PubMed 21343390Choi SW, Kim JY, Park JY, Cha IH, Kim J, Lee S. Expression of carbonic anhydrase IX is associated with postoperative recurrence and poor prognosis in surgically treated oral squamous cell carcinoma. Hum Pathol. 2008 Sep;39(9):1317-22. doi: 10.1016/j.humpath.2007.10.026. Epub 2008 Apr 28.
PubMed 18440050Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. doi: 10.1056/NEJMoa1011923.
PubMed 21561347Couvelard A, O'Toole D, Leek R, Turley H, Sauvanet A, Degott C, Ruszniewski P, Belghiti J, Harris AL, Gatter K, Pezzella F. Expression of hypoxia-inducible factors is correlated with the presence of a fibrotic focus and angiogenesis in pancreatic ductal adenocarcinomas. Histopathology. 2005 Jun;46(6):668-76. doi: 10.1111/j.1365-2559.2005.02160.x.
PubMed 15910598Coveler AL, Herman JM, Simeone DM, Chiorean EG. Localized Pancreatic Cancer: Multidisciplinary Management. Am Soc Clin Oncol Educ Book. 2016;35:e217-26. doi: 10.1200/EDBK_160827.
PubMed 27249726Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
PubMed 19097774Erkan M, Kurtoglu M, Kleeff J. The role of hypoxia in pancreatic cancer: a potential therapeutic target? Expert Rev Gastroenterol Hepatol. 2016;10(3):301-16. doi: 10.1586/17474124.2016.1117386. Epub 2015 Nov 27.
PubMed 26560854Gieling RG, Parker CA, De Costa LA, Robertson N, Harris AL, Stratford IJ, Williams KJ. Inhibition of carbonic anhydrase activity modifies the toxicity of doxorubicin and melphalan in tumour cells in vitro. J Enzyme Inhib Med Chem. 2013 Apr;28(2):360-9. doi: 10.3109/14756366.2012.736979. Epub 2012 Nov 19.
PubMed 23163664Guillaumond F, Leca J, Olivares O, Lavaut MN, Vidal N, Berthezene P, Dusetti NJ, Loncle C, Calvo E, Turrini O, Iovanna JL, Tomasini R, Vasseur S. Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3919-24. doi: 10.1073/pnas.1219555110. Epub 2013 Feb 13.
PubMed 23407165Kon-no H, Ishii G, Nagai K, Yoshida J, Nishimura M, Nara M, Fujii T, Murata Y, Miyamoto H, Ochiai A. Carbonic anhydrase IX expression is associated with tumor progression and a poor prognosis of lung adenocarcinoma. Lung Cancer. 2006 Dec;54(3):409-18. doi: 10.1016/j.lungcan.2006.08.017. Epub 2006 Oct 9.
PubMed 17030461Koong AC, Mehta VK, Le QT, Fisher GA, Terris DJ, Brown JM, Bastidas AJ, Vierra M. Pancreatic tumors show high levels of hypoxia. Int J Radiat Oncol Biol Phys. 2000 Nov 1;48(4):919-22. doi: 10.1016/s0360-3016(00)00803-8.
PubMed 11072146McDonald PC, Winum JY, Supuran CT, Dedhar S. Recent developments in targeting carbonic anhydrase IX for cancer therapeutics. Oncotarget. 2012 Jan;3(1):84-97. doi: 10.18632/oncotarget.422.
PubMed 22289741O JH, Lodge MA, Wahl RL. Practical PERCIST: A Simplified Guide to PET Response Criteria in Solid Tumors 1.0. Radiology. 2016 Aug;280(2):576-84. doi: 10.1148/radiol.2016142043. Epub 2016 Feb 24.
PubMed 26909647
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-center, Phase 1b Study to Investigate the Safety and Tolerability of SLC-0111 (WBI-5111) in Combination With Gemcitabine in Metastatic Pancreatic Ductal Adenocarcinoma Subjects Positive for Carbonic Anhydrase IX
- ClinicalTrials.gov ID
- NCT03450018
- Acronym / sponsor ID
- SLC-0111-17-01 / H17-02841
- Keywords
- Gemcitabine, SLC-0111, PDAC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Changing treatment landscape: The availability of nab-paclitaxel with gemcitabine in the second-line setting has changed the feasibility of further recruitment and potential long-term development opportunities of SLC-0111 with gemcitabine alone.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- British Columbia Cancer AgencyUniversity, hospital or other
- Collaborators
- Canadian Cancer Society (CCS), SignalChem Lifesciences Corporation
- Study start
- 10 Jan 2019 (actual)
- Primary completion
- 16 May 2024 (actual)
- Study completion
- 16 May 2024 (actual)
- First posted
- 1 Mar 2018 (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 multi-center, open-label Phase 1b study of SLC-0111 (oral) in combination with IV gemcitabine in CA IX positive subjects with mPDAC and comprises of 2 parts:
- Part 1: Dose Escalation
- Part 2: Dose Expansion
Detailed description
This is a multi-center, open-label Phase 1b study of SLC-0111 (oral) in combination with IV gemcitabine in CA IX positive subjects with mPDAC and comprises of 2 parts:
- Part 1: Dose Escalation
- Part 2: Dose Expansion
Biopsy or archival tissue will be collected and tested for the presence of CAIX via Immunohistochemistry (IHC) and only subjects positive for CAIX will be enrolled in the dose-escalation and dose-expansion parts. Part 2 can only begin after a dosing regimen has been characterized in Part 1. Subjects who participated in Part 1 of study will not be eligible to participate in Part 2.
The dose escalation will aim to identify the safety, tolerability and MTD of the oral formulation of SLC-0111 in combination with IV gemcitabine. Additional subjects may be enrolled at the MTD in dose expansion cohort. Data collected will allow evaluation of safety, tolerability, PK, Pharmacodynamics (PD) and tumour response of SLC-0111 in combination with gemcitabine.
A traditional 3 + 3 dose escalation design will be utilized for this study. Cohorts (same dose level) of 3 to 6 evaluable subjects will participate in a dose escalation scheme in which the dose of SLC-0111 will be increased in each consecutive cohort. Dose escalation to a new cohort of subjects will occur after review of available Cycle 1 data. The dose of SLC-0111 will be escalated based on Table 1 and Table 2 in the protocol. Based on emerging data alternative dosing schedules, or dose reductions may be considered. Gemcitabine will be administered at the standard dose (1000 mg/m^2) and schedule (day 1, 8, and 15 of each cycle) but dose reductions may be considered if necessary.
- Each cohort will initially consist of up to 3 subjects.
- If none of the first 3 subjects in a cohort demonstrates dose limiting toxicities (DLTs), then the cohort will be declared safe and the next cohort will be opened for enrollment
- If 1 of the first 3 subjects in a cohort demonstrates DLTs, then 3 additional subjects will be accrued to that cohort for a total of 6 subjects
- If 1 out of 6 subjects in a cohort demonstrates DLTs, then the cohort will be declared safe and the next cohort (n=3)will be opened for enrollment
- If 2 or more subjects in a cohort demonstrates DLTs, that cohort will be declared to exceed the MTD
Following the identification of a Cohort that exceeds the MTD, the next lowest dose, or an intermediate dose level may be further explored.
The MTD will be defined as the highest dose level at which no more than 1 of 6 subjects demonstrates DLTs.
Intra-subject dose escalation will not be allowed in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a traditional Phase I "3+3" study designed to identify the MTD by assessment of DLT of SLC-0111. Sample size estimates are not statistically based, but are based on acquisition of appropriate numbers of subjects to adequately describe the safety, tolerability, PK, and PD of SLC-0111 in combination with gemcitabine. Up to 18 subjects are anticipated to be enrolled in the dose escalation part; however, the actual number recruited will be dependent upon the number of dose escalations. Dose expansion (Part 2) may enroll up to 12 subjects.
| Arm | Type | Receives |
|---|---|---|
| SLC-0111 + Gemcitabine | Experimental | Drug: SLC-0111, Drug: Gemcitabine InjectionDose Level 1 - SLC-0111 (500 mg/day PO daily for 28 days) and Gemcitabine (1000 mg/m^2 IV on day 1, 8, and 15) Dose Level 2 - SLC-0111 (750 mg/day PO daily for 28 days) and Gemcitabine (1000 mg/m^2 IV on day 1, 8, and 15) Dose Level 3 - SLC-0111 (1000 mg/day PO daily for 28 days) and Gemcitabine (1000 mg/m^2 IV on day 1, 8, and 15) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (17 listed)
- Subjects negative for CAIX via IHC (biopsy or archival tissue)
- Previous treatment with any known CAIX Inhibitor
- Females who are pregnant, planning to become pregnant or breastfeeding.
- Severe cardiac disease which has required hospitalization within the past 3 months or which functionally limits a patient.
- Severe respiratory illness requiring supplemental oxygen or that significantly impacts functional status in daily life.
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 |
|---|---|---|
| SLC-0111Also: WBI-5111Oral SLC-0111 | Drug | SLC-0111 + Gemcitabine |
| Gemcitabine InjectionAlso: Gemcitabine1000 mg/m^2 IV | Drug | SLC-0111 + Gemcitabine |
Primary outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: Up to Safety Follow-Up Visit (30 days +/- 7 days after permanently stopping study treatment)
Adverse events (AEs) as assessed by CTCAE v5.0 will be determined by changes in safety assessments, including laboratory parameters, vital signs, ECG and physical examinations.
13 secondary outcomes
The maximum tolerated dose [MTD] of SLC-0111 in combination with gemcitabine
Time frame: Up to Safety Follow-Up Visit (30 days +/- 7 days after permanently stopping study treatment)
Maximum Plasma Concentration [Cmax]
Time frame: Up to 4 years
Time to Reach Maximum Plasma Concentraiton [Tmax]
Time frame: Up to 4 years
Elimination Rate Constant from the Central Compartment [Kel]
Time frame: Up to 4 years
Volume of Distribution During Terminal Phase after Intravenous Administration [Vz]
Time frame: Up to 4 years
Area Under the Concentration-Time Curve from Zero up to a Definite Time T [AUC(0-T)]
Time frame: Up to 4 years
Area Under the Concentration-Time Curve from Zero up to Infinity [AUC(0-inf)]
Time frame: Up to 4 years
Elimination Half-Life
Time frame: Up to 4 years
Determine the Recommended Phase II Dose of SLC-0111 in combination with gemcitabine
Time frame: Up to 2 years
Objective Response Rate [ORR] as Assessed by RECIST 1.1
Time frame: Up to 1 year
Progression-Free Survival [PFS] as Assessed by RECIST 1.1
Time frame: Up to 1 year
Duration of Response as Assessed by RECIST 1.1
Time frame: Up to 2 years
Overall Survival [OS]
Time frame: Up to the end of the study
Results and safety
The study was stopped early (reason given: Changing treatment landscape: The availability of nab-paclitaxel with gemcitabine in the second-line setting has changed the feasibility of further recruitment and potential long-term development opportunities of SLC-0111 with gemcitabine alone.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2024.
- Background: PubMed 21778770Assaf E, Verlinde-Carvalho M, Delbaldo C, Grenier J, Sellam Z, Pouessel D, Bouaita L, Baumgaertner I, Sobhani I, Tayar C, Paul M, Culine S. 5-fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma. Oncology. 2011;80(5-6):301-6. doi: 10.1159/000329803. Epub 2011 Jul 18.
- Background: PubMed 9196156Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. doi: 10.1200/JCO.1997.15.6.2403.
- Background: PubMed 21343390Chang Q, Jurisica I, Do T, Hedley DW. Hypoxia predicts aggressive growth and spontaneous metastasis formation from orthotopically grown primary xenografts of human pancreatic cancer. Cancer Res. 2011 Apr 15;71(8):3110-20. doi: 10.1158/0008-5472.CAN-10-4049. Epub 2011 Feb 22.
- Background: PubMed 18440050Choi SW, Kim JY, Park JY, Cha IH, Kim J, Lee S. Expression of carbonic anhydrase IX is associated with postoperative recurrence and poor prognosis in surgically treated oral squamous cell carcinoma. Hum Pathol. 2008 Sep;39(9):1317-22. doi: 10.1016/j.humpath.2007.10.026. Epub 2008 Apr 28.
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- 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.
Daniel J Renouf, MD principal investigator
BC Cancer - Vancouver
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SLC-0111 and Gemcitabine Injection in people with Metastatic Pancreatic Ductal Adenocarcinoma, run by British Columbia Cancer Agency at 2 sites in Canada.
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 0 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: stopped early, as of the sponsor's last update on 24 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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 combined 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.
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?
The study was stopped early (reason given: Changing treatment landscape: The availability of nab-paclitaxel with gemcitabine in the second-line setting has changed the feasibility of further recruitment and potential long-term development opportunities of SLC-0111 with gemcitabine alone.). Results are not available in the source record.
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?
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (time frame: Up to Safety Follow-Up Visit (30 days +/- 7 days after permanently stopping study treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03450018, which also lists 27 linked publications.
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 24 May 2024.