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Pilot Study Of Safety And Feasibility Of GI-4000, An Inactivated Recombinant Saccharomyces Cerevisiae Expressing Mutant Ras Protein Combined With Adoptive Transfer And Chemoradiation in Locally Advanced Pancreatic Cancer

Phase 1
18 Years
Not Enrolling
Pancreatic Cancer

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Trial Information

Pilot Study Of Safety And Feasibility Of GI-4000, An Inactivated Recombinant Saccharomyces Cerevisiae Expressing Mutant Ras Protein Combined With Adoptive Transfer And Chemoradiation in Locally Advanced Pancreatic Cancer

This Phase I/Pilot study will assess the safety and feasibility of the GI-4000 series
vaccine with or without adoptive T cell transfer in subjects with locally advanced
pancreatic cancer undergoing chemotherapy, radiotherapy, and surgical resection. Subjects
will be randomized to either ARM A (GI-4000vaccine) or ARM B (GI-4000 vaccine and activated
T cell transfer). All subjects will undergo apheresis of mononuclear cells immediately
before receiving four cycles of gemcitabine/oxaliplatin (GemOx) chemotherapy ("immune
preservation phase"). After the completion of chemotherapy, the apheresis product will be
reinfused, and the subjects will enter the "priming phase," in which two biweekly doses
(dose #1 and #2) of the appropriate GI-4000 vaccine (the one that best matches the mutations
found in the patient's tumor) and a single dose of the Prevnar pneumococcal conjugate
vaccine will be administered. At this time, those subjects who have not developed distant
metastatic disease by CT/MRI will undergo chemoradiation, with ARM B subjects receiving a
second apheresis immediately prior to the initiation of the chemoradiation. The pheresed
product will be activated and expanded ex vivo and reinfused after chemoradiation is
completed. All subjects will receive two more biweekly boosts of the GI-4000 vaccine (doses
#3 and #4) while undergoing restaging with CT/MRI ("boosting phase"). Those who have not
developed metastatic disease will undergo surgical evaluation for tumor resection. Patients
who undergo R0 or R1 resection will receive up to three more weekly doses of GI-4000 prior
to the initiation of adjuvant gemcitabine, monthly doses of GI-4000 during the four cycles
of gemcitabine chemotherapy, and monthly GI-4000 doses thereafter. At the end of
gemcitabine chemotherapy, apheresis will be performed for endpoint correlative studies.
Those who are not candidates for surgery or whose tumors are not completely resected will
continue to receive GI-4000 monthly booster vaccination.

Inclusion Criteria:

Adult patients with untreated, locally advanced pancreatic adenocarcinoma that expresses a
GI-4000 related k-ras oncoprotein.

1. Histologically-confirmed pancreatic adenocarcinoma that expresses one of the
GI-4000-related k-ras oncoproteins (G12V, G12C, G12D, Q61L, or Q61R)

2. Locally advanced disease, (stages I-III, i.e no evidence of metastasis outside the
pancreas and its regional lymph nodes). Preferred subjects for entry into the study
are those with borderline resectable disease, as defined by:

- tumor that encases a short segment of the hepatic artery without extension to
the celiac axis and that is amenable to resection and reconstruction, OR

- tumor that abuts the superior mesenteric artery and that involves <180 degrees
of the circumference of the artery, OR

- short-segment occlusion of the superior mesenteric vein, portal vein, or their
confluence with a suitable option available for vascular reconstruction because
the veins are normal above and below the area of tumor involvement.

3. Age >18 years

4. ECOG performance status 0 or 1

5. Normal organ and bone marrow function as defined by:

Absolute neutrophil count > 1,500/μl Platelets > 100,000/μl AST(SGOT)/ALT(SGPT)< 2.5
X institutional upper limit of normal Bilirubin < 2.0 mg/dL unless due to bile duct
blockage by tumor Creatinine < 1.5 x ULN

6. A biliary stent 9F or biliary bypass before treatment, if tumor-related biliary
obstruction is present

7. The ability to sustain adequate hydration and nutrition (>1500 cal/d) by oral intake
or access for supplemental enteral feeding (nasoenteral tube, feeding jejunostomy or

8. Patients must have measurable disease by radiographic imaging, as defined by 1 lesion
that can be accurately measured in at least one dimension (longest diameter to be
recorded) as 20 mm with conventional techniques or 10 mm with spiral CT scanning.
Marker elevation alone is insufficient for entry.

9. Ability to understand and the willingness to sign a written informed consent

10. Adequate venous or catheter access and ability to tolerate apheresis.

Exclusion Criteria:

1. Tumor metastatic to peritoneum, liver or other organs

2. Tumor that is clearly resectable for curative intent

3. Prior chemotherapy, radiation therapy, targeted therapy, or immunotherapy for
pancreatic cancer.

4. Receipt of any other investigational agents within 30 days prior to screening

5. Known HIV positive

6. A major surgical procedure or significant traumatic injury within 28 days prior to
anticipated initiation of chemotherapy, an anticipated major surgical procedure
during the course of the study, or a minor surgical procedure (laparoscopy, fine
needle aspiration, or core biopsy) within 7 days of anticipated initiation of

7. Serious non-healing wounds, ulcers, or bone fractures

8. Pregnancy or ongoing breast-feeding, as chemotherapy may pose substantial risk to the

9. Patients whose treatment plan would require treating >50% of the liver to a dose
greater than 30 Gy or treating > 50% of the total kidney volume to a dose greater
than 18 Gy

10. Positive scratch test (immediate hypersensitivity, IgE mediated) to S. cerevisiae.

11. Active autoimmune disease requiring immunosuppressive therapy

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate the feasibility of incorporating GI-4000 vaccine and activated T-cell infusion into a regimen of chemotherapy, radiation, and surgical resection to treat locally advanced pancreatic cancer.

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Peter J. O'Dwyer, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pennsylvania


United States: Food and Drug Administration

Study ID:




Start Date:

January 2008

Completion Date:

October 2009

Related Keywords:

  • Pancreatic Cancer
  • Pancreatic Cancer
  • Pancreatic Neoplasms