Pancreatic AdenocarcinomaPhase 1/2NCT03225989
Trial Investigating an Immunostimulatory Oncolytic Adenovirus for Cancer
A Phase 1/2 study testing LOAd703 in people with Pancreatic Adenocarcinoma and Ovarian Cancer, run by Lokon Pharma AB at 2 sites in Sweden.
Trial summary
This Phase I/II trial evaluates LOAd703 in patients with cancer (pancreatic, biliary, colorectal or ovarian) together with their standard of care chemotherapy or using gemcitabine immune-conditioning. LOAd703 is administered by intratumoral image-guided injections. Maximum 50 patients can be enrolled. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Adenocarcinoma, Ovarian Cancer, Biliary Carcinoma
- What is being tested?
- LOAd703
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 2 sitesSweden
- Study dates
- 1 Mar 2018to 22 Aug 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Have histologic or cytologic evidence of colorectal carcinoma (CRC), pancreatic carcinoma (PC), biliary cancer, or epithelial ovarian carcinoma (EOC which may encompass epithelial ovarian, fallopian tube or primary peritoneal carcinoma).
- Have advanced disease, defined as cancer that is either metastatic or locally advanced, unresectable, and for which radiotherapy or other locoregional therapies are not considered treatment of choice but systemic chemotherapy or no therapy is planned.
- Have one of the following treatment situations apply:
- Colorectal carcinoma (CRC) I. A patient with refractory or recurrent metastatic CRC who has either received all conventional therapy; or is entering a "resting" phase between reasonable conventional treatments. II. A patient who is amenable to treatment with LOAd703 plus gemcitabine as a single agent conditioning regimen.
- Pancreatic cancer I. A patient with either locally advanced, unresectable or metastatic disease who is eligible to receive any line of conventional treatment consisting of gemcitabine and/or nab-paclitaxel. II. A patient who is amenable to treatment with LOAd703 as an "add-on" to standard-of-care gemcitabine-based or nab-paclitaxel- based regimens or gemcitabine or nab-paclitaxel as single agents. c. Biliary cancer I. A patient with either locally advanced unresectable or metastatic biliary cancer who is either treatment-naïve or has received any number of lines of treatment. II. Patient who is amenable to treatment with LOAd703 as an "add-on" to standard-of-care treatment consisting of gemcitabine combined with other agents (e.g. gemcitabine/low-dose cisplatin, gemcitabine/oxaliplatin, etc) in the first line setting or gemcitabine in a combination regimen or as a single agent in latter lines of treatment. d. Ovarian Cancer I. A patient with either epithelial ovarian, fallopian tube or primary peritoneal carcinoma.
- The patient has either:
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- Residual disease following first-line standard-of-care combination chemotherapy. ii) Platinum-sensitive disease (platinum free interval ≥ 6 months) in early relapse following first-line standard-of care combination chemotherapy. iii) Platinum-resistant disease and received at least 3 lines of standard treatment. These treatments should have included bevacizumab and/or PARP inhibitors if they are reasonable candidates for such. III. Amenable to treatment with LOAd703 as an "add-on" to standard-of-care paclitaxel-based regimens (excluding bevacizumab), paclitaxel as a single agent, or gemcitabine as a single agent.
- Have a disease burden that is considered low (i.e. low tumor burden), which is defined on a patient-by-patient basis as per principal investigator's discretion. A rough guideline for defining low tumor burden is that the sum of the product of the bidimensional measurements for all lesions is < 70 cm2.
- Have a measurable disease by standard imaging techniques per RECIST criteria. Measurable lesions must be outside of any prior radiation field(s), unless disease progression has been documented at that disease site subsequent to radiation.
- At least one non-irradiated (or irradiated but disease progression documented at the site subsequent to radiation) lesion must be suitable for image-guided intratumoral injection and needle biopsy.
- Be medically suited to sedation if required during intratumoral injections.
- Be at least 18 years-old.
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
- Have no remaining acute toxic effects from previous anticancer therapy > grade 1 except for any grade of alopecia.
- Have adequate baseline organ/hematological function, as demonstrated by the following:
- Absolute neutrophil count (ANC) ≥1.0 x 109/l
- Hemoglobin ≥9 g/dl
- Platelet count ≥ 100 x 109/l
- Bilirubin < 1.5 times the institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 (3, if liver metastases are present) times the institutional ULN.
- Serum creatinine <2 times the institutional ULN or calculated creatinine clearance >35 mL/min
- Prothrombin (INR)<1.5 or prothrombin time (PT) <1.5 ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) ≤ 1.5 times the ULN.
- The patient must understand and be willing to provide written informed consent.
Who cannot join
- Any concurrent treatment that would compromise the study including but not limited to continuous high dose corticosteroids (>0.5mg/kg), lymphodepleting antibodies or cytotoxic agents.
- Treatment with high dose immune inhibitors including lymphotoxic monoclonal antibodies such as alemtuzumab (CampathR), or sirolimus (RapamuneR) and its analogs, biological therapy, cytotoxic agents or any investigational agents within 21 days of registration.
- Ovarian carcinoma patients should not be eligible to PARP inhibitor treatment.
- Patients on warfarin (or other anti-coagulants) are not eligible.
- Women who are pregnant, lactating, or planning to become pregnant during the study period, or women of childbearing potential who are not using acceptable contraceptive methods. A woman is considered of childbearing potential if she is not surgically sterile or is less than 1 year since last menstrual period. Acceptable contraceptive methods are: combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion and vasectomized partner.
- Men who do not consent to the use of condom during intercourse during study participation.
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- Known active hepatitis B or C infection, or HIV infection.
- Patients with active, severe, autoimmune disease.
- Uncontrolled intercurrent illness including but not limited to psychiatric illness/social situations that in the opinion of the Investigator would compromise compliance of study requirements or put the patient at unacceptable risk.
- Other malignancies within the past 2 years (not including basal and squamous cell carcinoma of the skin, localized prostate cancer or in situ cervix carcinoma).
- Patients must agree to not to vaccinate with living vaccines during participation in the trial.
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites
Karolinska University Hospital, Huddinge
Stockholm, 141 86
Uppsala University Hospital
Uppsala, 75185
About this study
Official title: Phase I/II Trial Investigating an Immunostimulatory Oncolytic Adenovirus for Cancer
This Phase I/II trial evaluates LOAd703 in patients with cancer (pancreatic, biliary, colorectal or ovarian) together with their standard of care chemotherapy or using gemcitabine immune-conditioning. LOAd703 is administered by intratumoral image-guided injections. Maximum 50 patients can be enrolled.
LOAd703 is an immunostimulatory gene therapy using an selection replication competent adenovirus as a gene vehicle. The virus is derived from serotype 5 adenovirus with the fiber from serotype 35. It expresses the transgenes trimerized membrane-bound isoleucine zipper (TMZ) TMZ-CD40L and 41BBL under control of a cytomegalovirus (CMV) promoter.
Read the detailed description
The trial is a Phase I/II trial evaluating the effect of LOAd703 in patients with pancreatic cancer, biliary cancer, ovarian cancer and colorectal cancer. LOAd703 is an oncolytic adenovirus serotype 5/35 encoding immunostimulatory transgenes: TMZ-CD40L and 41BBL. In Phase I, three doses (total viral load - 1x10e11, 5x10e11, 1x10e12 viral particles (VP)) of LOAd703 will be tested as add-on to standard of care or immune-conditioning gemcitabine chemotherapy. 8 treatments of LOAd703 will be delivered by image-guided intratumoral injection at the same time of chemotherapy. In Phase II stage of the study, patients will be treated at maximum tolerated dose/maximum tolerated study dose as defined in the Phase I stage. In both phases: tumor biopsies, blood samples and radiological imaging will be performed to evaluate safety, effect and mechanisms of action. Further, patients will be subjected to oral and rectal swabs, and urine sampling to determine virus shedding. The patients will be monitored for time to progression, progression free survival and overall survival.
- Being tested
- LOAd703
- Medical subject headings
- Ovarian Neoplasms, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LOAd703Drug
Oncolytic adenovirus serotype 5/35 encoding TMZ-CD40L and 4-1BBL
| Study group | Role | What they receive |
|---|---|---|
| LOAd703 | Experimental | LOAd703 oncolytic adenovirus administered add-on to standard of care chemotherapy or gemcitabine immune-conditioning if standard of care is no longer an option (e.g. after last line) Receives: Drug: LOAd703 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: Toxicity Symptoms Graded According to CTCAE v4.03.
The toxicity symptoms were graded according to CTCAE v4.03.
Measured: Up to 50 weeks
Immune Reactions to LOAd703 Virus as Assessed by Anti-adenovirus Ig ELISA
Fold change between baseline and evaluation visit for anti-adenovirus antibodies (LOAd703).
The baseline is the last available measurement taken before the first LOAd703 treatment. Evaluation is a measurement taken from subjects receiving at least 3 LOAd703 treatments.
Measured: Up to 50 weeks
Secondary outcomes (7)
Response on Tumor Size by Dose and Cancer Diagnosis
Local and distant anti-tumoral size changes assessed by appropriate imaging accordingly to RECIST 1.1. Complete Response (CR), complete macroscopic disappearance of all tumors; Partial Response (PR), a reduction of at least 30% in the sum of all tumor diameters from baseline; one/more lesions fulfilling the criteria for PR and other/others for progressive disease (PD); Stable disease (SD), Neither PR nor PD; Progressive disease (PD), at least 20% increase in the sum of all tumor diameters from the smallest tumor size and/or the appearance of new tumor lesion/s; Overall response rate (ORR) = CR + PR; Clinical benefit rate (CBR) = CR + PR + SD.
Measured: Up to 50 weeks
Overall Survival
Months of overall survival (OS) from registration by dose and cancer diagnosis
Measured: From registration date to date of death, assessed up to 40 months
Time to Progression
Time to progression from registration by dose and cancer diagnosis
Measured: From registration date to date of progression, assessed up to 40 months
Progression Free Survival
Months of progression free survival (PFS) from registration by dose and cancer diagnosis
Measured: From registration date to date of progression, or date of death, which ever came first, assessed up to 40 months
Systemic Immune Activation
Percentage of participants with upregulated immune marker in blood at evaluation as compared to baseline.
The baseline is the last available measurement taken before the first LOAd703 treatment. Evaluation is a measurement taken from subjects receiving at least 3 LOAd703 treatments.
Measured: Up to 50 weeks
Immune Cell Activation
Fold change between baseline and evaluation visit for CD8+ CD3+ T cells activation evaluated by flow cytometry.
The baseline is the last available measurement taken before the first LOAd703 treatment. Evaluation is a measurement taken from subjects receiving at least 3 LOAd703 treatments.
Measured: Up to 50 weeks
Presence of LOAd703 Virus in Blood
Percentage of PK samples analyzed that were positive for viral DNA/ml in serum.
Measured: Up to 50 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start1 Mar 2018
- Primary completion22 Aug 2023
- Study completion22 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pancreatic AdenocarcinomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Participants treated with LOAd703 at three dose levels (5x10e10 VP, 1x10e11 VP, 5x10e11 VP) and SOC tailored to the indication
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lokon Pharma AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Uppsala University
- Responsible party
- Sponsor
- Investigators
- Angelica Loskog, PhD, Study chair, Lokon Pharma AB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03225989
- Sponsor's protocol ID
- LOKON002
- Status last verified
- Oct 2024
- First submitted
- 4 Jul 2017
- Last updated
- 19 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- 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 19 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial Investigating an Immunostimulatory Oncolytic Adenovirus for Cancer
- ClinicalTrials.gov ID
- NCT03225989
- Acronym / sponsor ID
- LOKON002
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Lokon Pharma ABIndustry (pharma, biotech, devices)
- Collaborators
- Uppsala University
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 22 Aug 2023 (actual)
- Study completion
- 22 Aug 2023 (actual)
- First posted
- 21 Jul 2017 (actual)
- Results
- Posted 19 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase I/II trial evaluates LOAd703 in patients with cancer (pancreatic, biliary, colorectal or ovarian) together with their standard of care chemotherapy or using gemcitabine immune-conditioning. LOAd703 is administered by intratumoral image-guided injections. Maximum 50 patients can be enrolled.
LOAd703 is an immunostimulatory gene therapy using an selection replication competent adenovirus as a gene vehicle. The virus is derived from serotype 5 adenovirus with the fiber from serotype 35. It expresses the transgenes trimerized membrane-bound isoleucine zipper (TMZ) TMZ-CD40L and 41BBL under control of a cytomegalovirus (CMV) promoter.
Detailed description
The trial is a Phase I/II trial evaluating the effect of LOAd703 in patients with pancreatic cancer, biliary cancer, ovarian cancer and colorectal cancer. LOAd703 is an oncolytic adenovirus serotype 5/35 encoding immunostimulatory transgenes: TMZ-CD40L and 41BBL. In Phase I, three doses (total viral load - 1x10e11, 5x10e11, 1x10e12 viral particles (VP)) of LOAd703 will be tested as add-on to standard of care or immune-conditioning gemcitabine chemotherapy. 8 treatments of LOAd703 will be delivered by image-guided intratumoral injection at the same time of chemotherapy. In Phase II stage of the study, patients will be treated at maximum tolerated dose/maximum tolerated study dose as defined in the Phase I stage. In both phases: tumor biopsies, blood samples and radiological imaging will be performed to evaluate safety, effect and mechanisms of action. Further, patients will be subjected to oral and rectal swabs, and urine sampling to determine virus shedding. The patients will be monitored for time to progression, progression free survival and overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Participants treated with LOAd703 at three dose levels (5x10e10 VP, 1x10e11 VP, 5x10e11 VP) and SOC tailored to the indication
| Arm | Type | Receives |
|---|---|---|
| LOAd703 | Experimental | Drug: LOAd703LOAd703 oncolytic adenovirus administered add-on to standard of care chemotherapy or gemcitabine immune-conditioning if standard of care is no longer an option (e.g. after last line) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Have histologic or cytologic evidence of colorectal carcinoma (CRC), pancreatic carcinoma (PC), biliary cancer, or epithelial ovarian carcinoma (EOC which may encompass epithelial ovarian, fallopian tube or primary peritoneal carcinoma).
- Have advanced disease, defined as cancer that is either metastatic or locally advanced, unresectable, and for which radiotherapy or other locoregional therapies are not considered treatment of choice but systemic chemotherapy or no therapy is planned.
- Have one of the following treatment situations apply:
- Have a disease burden that is considered low (i.e. low tumor burden), which is defined on a patient-by-patient basis as per principal investigator's discretion. A rough guideline for defining low tumor burden is that the sum of the product of the bidimensional measurements for all lesions is < 70 cm2.
- Have a measurable disease by standard imaging techniques per RECIST criteria. Measurable lesions must be outside of any prior radiation field(s), unless disease progression has been documented at that disease site subsequent to radiation.
Key exclusion criteria (11 listed)
- Any concurrent treatment that would compromise the study including but not limited to continuous high dose corticosteroids (>0.5mg/kg), lymphodepleting antibodies or cytotoxic agents.
- Treatment with high dose immune inhibitors including lymphotoxic monoclonal antibodies such as alemtuzumab (CampathR), or sirolimus (RapamuneR) and its analogs, biological therapy, cytotoxic agents or any investigational agents within 21 days of registration.
- Ovarian carcinoma patients should not be eligible to PARP inhibitor treatment.
- Patients on warfarin (or other anti-coagulants) are not eligible.
- Women who are pregnant, lactating, or planning to become pregnant during the study period, or women of childbearing potential who are not using acceptable contraceptive methods. A woman is considered of childbearing potential if she is not surgically sterile or is less than 1 year since last menstrual period. Acceptable contraceptive methods are: combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion and vasectomized partner.
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 |
|---|---|---|
| LOAd703Oncolytic adenovirus serotype 5/35 encoding TMZ-CD40L and 4-1BBL | Drug | LOAd703 |
Primary outcome
Safety: Toxicity Symptoms Graded According to CTCAE v4.03.
Time frame: Up to 50 weeks
The toxicity symptoms were graded according to CTCAE v4.03.
Immune Reactions to LOAd703 Virus as Assessed by Anti-adenovirus Ig ELISA
Time frame: Up to 50 weeks
Fold change between baseline and evaluation visit for anti-adenovirus antibodies (LOAd703). The baseline is the last available measurement taken before the first LOAd703 treatment. Evaluation is a measurement taken from subjects receiving at least 3 LOAd703 treatments.
7 secondary outcomes
Response on Tumor Size by Dose and Cancer Diagnosis
Time frame: Up to 50 weeks
Overall Survival
Time frame: From registration date to date of death, assessed up to 40 months
Time to Progression
Time frame: From registration date to date of progression, assessed up to 40 months
Progression Free Survival
Time frame: From registration date to date of progression, or date of death, which ever came first, assessed up to 40 months
Systemic Immune Activation
Time frame: Up to 50 weeks
Immune Cell Activation
Time frame: Up to 50 weeks
Presence of LOAd703 Virus in Blood
Time frame: Up to 50 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Angelica Loskog, PhD study chair
Lokon Pharma AB
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 LOAd703 in people with Pancreatic Adenocarcinoma and Ovarian Cancer, run by Lokon Pharma AB at 2 sites in Sweden.
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 23 inclusion and 11 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 19 Nov 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 Sweden. 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?
Yes. Results are posted in the registry (first posted 19 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Safety: Toxicity Symptoms Graded According to CTCAE v4.03. (time frame: Up to 50 weeks). 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 19 Nov 2024.