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LOAd703 Oncolytic Virus Therapy for Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02705196
Recruitment Status : Recruiting
First Posted : March 10, 2016
Last Update Posted : October 15, 2019
Sponsor:
Information provided by (Responsible Party):
Lokon Pharma AB

Brief Summary:

The purpose of this study is to see if LOAd703 (an oncolytic adenovirus) can be safely given to patients with pancreatic cancer. The study will also evaluate whether or not intratumoral injection of LOAd703 will support current standard of care treatment to reduce the size of the tumor and improve survival of the patients.

Adenoviruses are known as the "common cold" virus and most individuals have had multiple infections during their lifetime. Oncolytic adenoviruses are adenoviruses that are modified so they cannot multiply and spread (known as replicating) properly in normal (e.g. healthy) cells, but instead, they infect and replicate very well in cancer cells. This strong replication leads to the death of the cancer cell. Oncolytic viruses have been evaluated in multiple clinical trials for cancer treatment during the past decade and been proven safe. It is common to have a fever the first day or two after virus injection since the immune system will react to the virus infection. The immune system can also kill cancer cells but to do so it needs to be properly stimulated. Oncolytic viruses alone do not seem to be strong enough to activate clinically relevant anti-cancer responses. However, it is thought that if additional immune system stimulators are added to the oncolytic viruses they may be able to result in clinical relevant antic-cancer responses.

LOAd703 is an oncolytic adenovirus that has been modified to include additional immune system stimulators. Specifically, genes that stimulate the immune system have been added to the oncolytic adenovirus. Once the oncolytic adenovirus infects the cancer cells, the genes will be expressed, resulting in activation of the immune response so it can attack and kill cancer cells.

In this study, LOAd703 will be given by intratumoral injections. It will be given in addition to standard of care treatment with gemcitabine and nab-paclitaxel +/- the anti-PD-L1 antibody atezolizumab. Because this is an experimental therapy, there will be extra visits for disease monitoring and samples accordingly to the detailed information below. The LOAd703 is an investigational agent not approved by the FDA.


Condition or disease Intervention/treatment Phase
Pancreatic Cancer Genetic: delolimogene mupadenorepvec Drug: gemcitabine Drug: nab-paclitaxel Biological: atezolizumab Phase 1 Phase 2

Detailed Description:

The research will be conducted at Baylor College of Medicine (BCM) and Baylor St. Luke's Medical Center (BSLMC).

All patients will receive standard of care treatment for their pancreatic cancer. Standard of care treatment will be gemcitabine in combination with nab-paclitaxel given on days 1, 8, and 15 of a 28 day cycle.

Arm 1: LOAd703 treatment will be initiated at day 15 of the first cycle and given every other week for 6 doses. Depending on the location of the tumor the injection of LOAd703 can be given in different ways. The most common route of injection is ultrasound-guided percutaneous injection, but endoscopic ultrasound-guidance will be used for some patients as appropriate. All patients will receive anti-anxiety drugs or sedation as needed for comfort during the procedure. This study evaluates different doses of LOAd703. All patients will receive six injections of LOAd703. If patients in either phase of the study are judged by the investigator to be deriving clinical benefit from LOAd703 once all scheduled injections have been administered, they will be eligible to receive up to 6 additional biweekly doses of LOAd703.

Arm 2: the same procedures as arm 1 in regard to LOAd703. In addition, the arm 2 patients will receive atezolizumab at a fixed dose, every chemotherapy cycle day 1. The treatments can continue until the final follow-up visit.

Follow-up visits: Besides visits to receive treatments, patients will continue to visit BCM/BSLMC or their local doctor for evaluation of health status and side effects. At some visits blood samples will be obtained. Some of the blood samples being obtained are considered standard of care to ensure patient safety for standard of care treatment and the LOAd703 injection. However, some blood and biopsy samples (in applicable patients) will be collected to be analyzed for the presence of LOAd703, atezolizumab tumor markers and immunology markers. The extra blood will be 5-15 ml (3 teaspoonfuls) of blood collected at the screening visit and at eight different time points both during treatment and after treatments are completed. Imaging of the tumor to determine tumor size will be done every two to three months, which is routine for the monitoring of patients with pancreatic cancer. Patients will actively participate in the study for about 9 months when the final follow-up visit will be scheduled. After their active participation is completed patients will continue to receive routine care and will be contacted by the study team every 3 months to provide follow up on the status of their disease.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/IIa Trial Evaluating Safety of LOAd703, an Armed Oncolytic Adenovirus for Pancreatic Cancer
Actual Study Start Date : November 2016
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1 Intratumoral LOAd703

Patients will receive gemcitabine intravenously at a dose of 1000mg/m2 + nab-paclitaxel 125 mg/m2 as per hospital standards. One cycle will be one dose of gemcitabine +nab-paclitaxel given on days 1, 8, and 15 of a 28 day cycle. LOAd703 will be given every other week for 6 doses starting on day 15 of the first cycle of chemotherapy. There is an option for an additional 6 doses if patients benefit from treatment.

The following LOAd703 doses will be evaluated:

Dose level 1: 5 X 10^10 viral particles per treatment Dose level 2: 1 X 10^11 viral particles per treatment Dose level 3: 5 X 10^11 viral particles per treatment

Genetic: delolimogene mupadenorepvec
oncolytic virus encoding TMZ-CD40L and 4-1BBL
Other Name: LOAd703

Drug: gemcitabine
chemotherapy
Other Name: Gemzar

Drug: nab-paclitaxel
chemotherapy
Other Name: Abraxane

Experimental: Arm 2: Intratumoral LOAd703 + atezolizumab

Patients will receive gemcitabine intravenously at a dose of 1000mg/m2 + nab-paclitaxel 125 mg/m2 as per hospital standards. One cycle will be one dose of gemcitabine +nab-paclitaxel given on days 1, 8, and 15 of a 28 day cycle. LOAd703 will be given every other week for 6 doses starting on day 15 of the first cycle of chemotherapy. There is an option for an additional 6 doses if patients benefit from treatment. A fixed dose of atezolizumab 1680 mg will be given every 4 weeks on day 1 of each chemotherapy cycle.

Patients will be assigned to the following LOAd703 doses:

Dose level 1: 1 X 10^11 viral particles per treatment Dose level 2: 5 X 10^11 viral particles per treatment

Genetic: delolimogene mupadenorepvec
oncolytic virus encoding TMZ-CD40L and 4-1BBL
Other Name: LOAd703

Drug: gemcitabine
chemotherapy
Other Name: Gemzar

Drug: nab-paclitaxel
chemotherapy
Other Name: Abraxane

Biological: atezolizumab
anti-PD-L1 antibody
Other Name: Tecentriq




Primary Outcome Measures :
  1. Number of patient with dose-limiting toxicities (DLTs) as evaluated accordingly to CTCAE 4.0 [ Time Frame: 9 months ]
    Maximum tolerated dose of multiple (6x) image-guided intratumoral injections of LOAd703 at three dose levels in combination with standard of care therapy


Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 9 months ]
    To determine the percentage of subjects achieving a partial response or better (according to RECIST 1.1) to repeat doses of LOAd703 (at the highest dose as determined in Phase I) combined with standard of care treatment with and without atezolizumab in pancreatic cancer.

  2. Overall Survival [ Time Frame: 6 months post last patient, last visit ]
    To determine the survival days post study initiation



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of ductal adenocarcinoma of the pancreas (PDAC).
  2. Low tumor burden with at least one lesion that is suitable for image-guided intratumoral injection and needle biopsy.
  3. The patient is not eligible for a complete surgical resection of their disease as evaluated by a radiologist and/or surgeon.
  4. Patients who may receive the injections endoscopically should be eligible for sedation.
  5. The patient must be eligible for standard of care treatment with gemcitabine +nab-paclitaxel.
  6. Age ≥ 18 yrs of age
  7. Females of childbearing potential must have a negative pregnancy test and agree to use contraception during on-study protocol treatment.
  8. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
  9. Absolute neutrophil count (ANC) ≥1.0 x 10^9/l, hemoglobin ≥9 g/dl, platelet count ≥ 100 x 10^9/l, prothrombin (INR) <1.5.
  10. Adequate hepatic function, with bilirubin < 1.5 x the ULN, and AST and ALT < 2.5 x ULN
  11. Adequate renal function with serum creatinine <2 x the ULN or creatinine clearance >30 mL/min
  12. The patient must provide informed consent.

Exclusion Criteria:

  1. Any concurrent treatment that would compromise the study including but not limited to continuous high dose corticosteroids (>10 mg/day of prednisone equivalence), lymphodepleting antibodies or cytotoxic agents.
  2. Treatment with high dose immune inhibitors including lymphotoxic monoclonal antibodies such as alemtuzumab (Campath), or rapamycin/rapalogs or cytotoxic agents within 21 days of registration
  3. Treatment with biologic therapy within 21 days of registration.
  4. Use of any investigational agents within 21 days of registration.
  5. The use of systemic immunostimulatory agents (including, but not limited to, interferons and IL-2) are prohibited within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment and during study treatment because these agents could potentially increase the risk for autoimmune conditions when given in combination with atezolizumab
  6. Pregnant or breastfeeding females.
  7. Known active hepatitis B or C infection, HIV infection or tuberculosis.
  8. Patients with active autoimmune disease or immune deficiency or previous Guillain-Barre syndrome. Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g. patients with psoriatic arthritis are excluded) are eligible for the study provide all of the following conditions are met:

    • Rash must cover <10% of body surface area
    • Disease is well controlled at baseline and requires only low-potency topical corticosteroids
    • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors or high-potency or oral corticosteroids within the previous 12 months
  9. 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.
  10. Other malignancies within the past 2 years (not including basal cell carcinoma of the skin, prostate cancer or in situ cervix carcinoma).
  11. Moderate to large volume ascites.
  12. History of leptomeningeal disease.
  13. Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (once monthly or more frequently)
  14. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis or evidence of active pneumonitis on screening chest computed tomography (CT) scan. However, history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  15. Unstable angina, uncontrolled cardiac arrhythmia, recent (within 3 months) history of myocardial infarction or stroke or New York Class III/IV congestive heart failure
  16. Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the study.
  17. Prior allogeneic stem cell or solid organ transplantation.
  18. History of severe allergic anaphylactic reactions to chimeric human or humanized antibodies or fusion proteins.
  19. Known hypersensitivity to CHO cell products or any component of the atezolizumab formulation.
  20. Live attenuated vaccines (e.g. FluMist) are prohibited within 4 weeks prior to initiation of study treatment, during atezolizumab treatment, and for 5 months after the final dose of atezolizumab.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02705196


Contacts
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Contact: Benjamin Musher, MD 713-798-4298

Locations
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United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Benjamin Musher, MD    713-798-4298    blmusher@bcm.edu   
Contact: Monica Francois    713-798-4951    Monica.Francois@bcm.edu   
Baylor St Luke's Medical Center Recruiting
Houston, Texas, United States, 77030
Contact: Benjamin Musher, MD    713-798-9732    blmusher@bcm.edu   
Contact: Monica Francois    713-798-4951    Monica.Francois@bcm.edu   
Sponsors and Collaborators
Lokon Pharma AB
Investigators
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Study Chair: Angelica Loskog, PhD Lokon Pharma AB

Additional Information:
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Responsible Party: Lokon Pharma AB
ClinicalTrials.gov Identifier: NCT02705196    
Other Study ID Numbers: LOKON001
First Posted: March 10, 2016    Key Record Dates
Last Update Posted: October 15, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Lokon Pharma AB:
oncolytic
adenovirus
pancreatic
cancer
LOKON
LOAd703
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Atezolizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs