Immunochemoradiotherapy in Patients With Pancreatic Cancer

NCT ID: NCT01342224

Last Updated: 2018-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2018-04-30

Brief Summary

This study will add an immunotherapy component to chemotherapy and radiation treatment in patients who have pancreatic cancer. The objective of this study is to see if the combined treatment is safe and feasible, and if a larger study is warranted.

Detailed Description

All study participants receive an initial 4 week course of intra-dermal vaccination with telomerase vaccine (GV1001) and immune adjuvant, granulocyte macrophage colony-stimulating factor (GM-CSF), along with a cycle of gemcitabine chemotherapy. This is followed by concurrent radiation therapy and low-dose intravenous (IV) gemcitabine chemotherapy given twice weekly followed by one additional dose of vaccine.

About 4 weeks (as late as 8 weeks) after chemotherapy and radiation treatment, participants with disease that can be removed by surgery will proceed to surgery. After recovery, immunochemotherapy will resume.

Participants with stable or responsive disease that is not able to be treated with surgery will proceed to immunochemotherapy.

Immunochemotherapy will consist of 2 cycles of telomerase vaccine with GM-CSF along with gemcitabine chemotherapy. Participants with disease that is not able to be treated with surgery, or that has worsened following immunochemoradiotherapy phase of treatment may continue on study with transition to immunochemotherapy phase of treatment. Tadalafil will be administered orally on a daily basis from start of therapy (Day 1) through completion of therapy with doses held only when required in the immediate perioperative period in patients who proceed to surgery.

Conditions

Locally Advanced Pancreatic Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

tadalafil and vaccination

Participants receive a 4-week course of vaccination with telomerase vaccine and GM-CSF by injection, along with a cycle of gemcitabine chemotherapy (IV). This is followed by radiation and gemcitabine given twice weekly then by another dose of vaccine.

Group Type: EXPERIMENTAL

tadalafil and vaccination

Intervention Type: BIOLOGICAL

Participants receive a 4-week course of vaccination with telomerase vaccine and GM-CSF by injection, along with a cycle of gemcitabine chemotherapy (IV). This is followed by radiation and gemcitabine given twice weekly then by another dose of vaccine. Four weeks after completion of chemotherapy and radiation, participants able to have surgical treatment will have surgery followed by vaccination and chemotherapy. Participants with stable or responsive disease that cannot be treated by surgery will have vaccination and chemotherapy with 2 cycles of telomerase vaccine with GM-CSF along with gemcitabine. Participants with unresectable and progressive disease after administration of vaccine, chemotherapy and radiation treatment may transition to vaccination and chemotherapy treatment.

Interventions

tadalafil and vaccination

Participants receive a 4-week course of vaccination with telomerase vaccine and GM-CSF by injection, along with a cycle of gemcitabine chemotherapy (IV). This is followed by radiation and gemcitabine given twice weekly then by another dose of vaccine. Four weeks after completion of chemotherapy and radiation, participants able to have surgical treatment will have surgery followed by vaccination and chemotherapy. Participants with stable or responsive disease that cannot be treated by surgery will have vaccination and chemotherapy with 2 cycles of telomerase vaccine with GM-CSF along with gemcitabine. Participants with unresectable and progressive disease after administration of vaccine, chemotherapy and radiation treatment may transition to vaccination and chemotherapy treatment.

Intervention Type: BIOLOGICAL

Other Intervention Names

tadalafil: Cialis; gemcitabine: Gemzar; telomerase vaccine: GV1001; GM-CSF: Sargramostim (Leukine)

Eligibility Criteria

Inclusion Criteria

Pancreatic adenocarcinoma proven by biopsy or cytology Locally advanced, unresectable disease with absence of distant metastatic disease. The presence of non-regional retroperitoneal or abdominal adenopathy is acceptable for inclusion.

OR

Borderline resectable pancreatic adenocarcinoma (any of the following):

• Tumor abutment or encasement of a short segment of hepatic artery (without evidence of tumor extension to the celiac artery) that is amenable to resection and reconstruction
• Tumor abutment of the superior mesenteric artery involving 180 degrees or less of the circumference of the artery and without encasement
• Impingement or narrowing of the superior mesenteric vein/portal vein or short-segment (< 2 cm) occlusion of the superior mesenteric vein, portal vein, or their confluence with a suitable option for vascular reconstruction
• Eastern Cooperative Oncology Group(ECOG)Performance Status 0 or 1
• Ability to give informed consent and comply with the protocol
• Women of childbearing potential must have a negative pregnancy test and must avoid becoming pregnant while on treatment. Men must avoid fathering a child while on treatment.
• Patients with a history of psychiatric illness must be judged able to understand fully the investigational nature of the study and the risks associated with the therapy.

Exclusion Criteria

• Age < 18 years
• History of other malignancy in the past 2 years except carcinoma in situ of the cervix or bladder, or non-melanomatous skin cancer
• Previous chemotherapy or radiation therapy for pancreatic cancer or previous radiation therapy to the target field
• Clinically active autoimmune disease or active infection
• History of heart attack (within 90 days) or stroke (within 6 months), or presence of hypertension requiring change in blood pressure medications in the last 4 weeks, hypotension, uncontrolled arrhythmias, heart failure (New York Heart Association (NYHA) Functional Classification ≥ Class 2 in last 6 months), unstable angina or angina occurring during sexual activity.
• Use of "nitrates" or nitroglycerin.
• History of hereditary degenerative retinal disorders including retinitis pigmentosa.
• Chronic systemic corticosteroid use at supra-physiologic doses (prednisone > 10 mg a day or equivalent)
• Use of recreational drugs called "poppers" like amyl nitrite and butyl nitrite.
• Laboratory values (performed within 14 days prior to enrollment) as follows:

• Neutrophil count < 1500 cells/µL
• Hemoglobin < 9 gm/dL (patients may be transfused to establish eligibility)
• Platelet count < 100,000 cells/µL
• Significant coagulopathy (INR > 1.5)
• Significant liver or renal dysfunction
• Other medical or psychiatric conditions that in the opinion of the Principal Investigator would preclude safe participation in protocol.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Providence Cancer Center, Earle A. Chiles Research Institute

OTHER

Sponsor Role: collaborator

Robert W. Franz Cancer Research Center

UNKNOWN

Sponsor Role: collaborator

Providence Health & Services

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Todd Crocenzi, MD

Role: PRINCIPAL_INVESTIGATOR

Providence Health & Services

Locations

Providence Health & Services

Portland, Oregon, United States

Countries

United States

References

Crocenzi T, Cottam B, Newell P, Wolf RF, Hansen PD, Hammill C, Solhjem MC, To YY, Greathouse A, Tormoen G, Jutric Z, Young K, Bahjat KS, Gough MJ, Crittenden MR. A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma. J Immunother Cancer. 2016 Aug 16;4:45. doi: 10.1186/s40425-016-0149-6. eCollection 2016.

Reference Type: DERIVED

PMID: 27532020 (View on PubMed)

Other Identifiers

PHS 10-141B

Identifier Type: -

Identifier Source: org_study_id