LOAd703 Oncolytic Virus Therapy for Pancreatic Cancer
| Status: | Recruiting |
|---|---|
| Conditions: | Cancer, Cancer, Pancreatic Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 1/10/2019 |
| Start Date: | November 2016 |
| End Date: | August 2020 |
| Contact: | Benjamin Musher, MD |
| Phone: | 713-798-4298 |
Phase I/IIa Trial Evaluating Safety of LOAd703, an Armed Oncolytic Adenovirus for Pancreatic Cancer
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. Because LOAd703 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.
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. Because LOAd703 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.
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. 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.
Phase I patients only: All of the six injections of LOAd703 will be done at BCM/BSLMC. The
patient will stay at BSLMC over night for evaluation after the first two doses of LOAd703. As
tolerated, the patient may be allowed to leave the hospital as soon as 4 hours after LOAd703
injection. Simultaneously to the LOAd703 treatments, and after the last LOAd703 injection,
patients will continue to receive standard of care treatment.
Phase IIa patients only: All of the six injections of LOAd703 will be done at BCM/BSLMC.
During this phase of the study Before the first and the fourth of the six LOAd703 injections,
a biopsy will be taken from the injected tumor (percutaneous needle biopsy or endoscopic
procedure depending on the method of LOAd703 administration) and optionally from an
uninjected tumor. Simultaneously to the LOAd703 treatments, and after the last LOAd703
injection, patients will continue to receive standard of care treatment.
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.
Follow-up visits: Besides visits to receive standard of care treatment, 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, 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
LOAd703 injections 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. 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.
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. 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.
Phase I patients only: All of the six injections of LOAd703 will be done at BCM/BSLMC. The
patient will stay at BSLMC over night for evaluation after the first two doses of LOAd703. As
tolerated, the patient may be allowed to leave the hospital as soon as 4 hours after LOAd703
injection. Simultaneously to the LOAd703 treatments, and after the last LOAd703 injection,
patients will continue to receive standard of care treatment.
Phase IIa patients only: All of the six injections of LOAd703 will be done at BCM/BSLMC.
During this phase of the study Before the first and the fourth of the six LOAd703 injections,
a biopsy will be taken from the injected tumor (percutaneous needle biopsy or endoscopic
procedure depending on the method of LOAd703 administration) and optionally from an
uninjected tumor. Simultaneously to the LOAd703 treatments, and after the last LOAd703
injection, patients will continue to receive standard of care treatment.
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.
Follow-up visits: Besides visits to receive standard of care treatment, 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, 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
LOAd703 injections 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. 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.
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 kidney 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 (>0.5mg/kg), lymphodepleting antibodies or
cytotoxic agents.
2. Treatment with high dose immune inhibitors including lymphotoxic monoclonal antibodies
such as campath, or rapamycin and its analogs 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. Pregnant or breastfeeding females.
6. Known active hepatitis B or C infection, or HIV infection.
7. 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.
8. Other malignancies within the past 2 years (not including basal cell carcinoma of the
skin, prostate cancer or in situ cervix carcinoma).
9. Moderate to large volume ascites.
10. Active autoimmune disease.
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sites
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1200 Moursund Street
Houston, Texas 77030
Houston, Texas 77030
(713) 798-4951
Phone: 713-798-4298
Baylor College of Medicine Baylor College of Medicine in Houston, the only private medical school...
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