Administration as a Biological Adjuvant in Clinically-Staged, Resectable Pancreatic Adenocarcinoma

NCT00600002 | Completed Phase 1 DMC

• 2 other identifiers: UCI 02-692003-2972
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The application of immunotherapeutic strategies that target the most potent antigen presenting cell, the dendritic cell (DC), are likely to substantially increase the magnitude of the anti-tumor immune response. Although there are issues of activation state and antigen load, mechanisms to increase the number of DCs available to the immune system are among the first steps in development of affective DC based immunotherapeutic strategies. The Central Hypothesis of our study is: Administration of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) to patients with pancreatic adenocarcinoma will result in enhance recruitment of DCs to the sentinel lymph node, into the peripheral blood, and/or tumor site. We propose performing a phase I, dose escalation, clinical trial of systemic and intra-tumoral GM-CSF administration for the treatment of pancreatic adenocarcinoma. This trial will be designed to assess toxicity and immunologic effects, principally dendritic cell recruitment. Patients with resectable pancreatic adenocarcinoma by clinical staging criteria will be eligible for enrollment. The trial we propose is a phase I clinical trial of the addition of GM-CSF as a biological adjuvant to standard care for patients with potentially resectable pancreatic adenocarcinoma.

Conditions

Resectable Pancreatic Adenocarcinoma; Pancreatic Cancer

Keywords

GM-CSF; Leukine

Outcome Measures

Primary Outcomes (1)

• Evaluate toxicity, dendritic cell recruitment, and immune parameters

  2 years

Secondary Outcomes (5)

• Evaluate patient survival

  2 years

• Evaluate progression free survival

  2 years

• Evaluate time to treatment failure

  2 years

• Evaluate quality of life

  2 years

• Evaluate biochemical markers

  2 years

Study Arms (1)

GM-CSF

EXPERIMENTAL

Cohort 1: 50 ug/m2 given Intravenous. Cohort 2: 150 ug/m2 given Intravenous. Cohort 3: 250 ug/m2 given Intravenous. Cohort 4: 0 ug/m2 and vehicle (normal saline) given Intra-tumoral. Cohort 5: 50 ug/m2 given Intra-tumoral. Cohort 6: 150 ug/m2 given Intra-tumoral. Cohort 7: 250 ug/m2 given Intra-tumoral.

Biological: GM-CSF

Interventions

GM-CSF BIOLOGICAL

Cohort 1: 50 ug/m2 given Intravenous. Cohort 2: 150 ug/m2 given Intravenous. Cohort 3: 250 ug/m2 given Intravenous. Cohort 4: 0 ug/m2 and vehicle (normal saline) given Intra-tumoral. Cohort 5: 50 ug/m2 given Intra-tumoral. Cohort 6: 150 ug/m2 given Intra-tumoral. Cohort 7: 250 ug/m2 given Intra-tumoral.

GM-CSF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histological proven adenocarcinoma of the pancreas with potentially resectable disease based upon clinical staging.
• Expected survival must be greater than three (3) months.
• A Karnofsky Performance Status (KPS) must be 70 or greater.
• Patients must be \>18 years of age. Because Leukine® is a "Pregnancy Category C" drug, female patients must be not be lactating and must be surgically sterile (via hysterectomy or bilateral tubal ligation), postmenopausal, or using acceptable methods of contraception if they are of child bearing potential. Female patients of childbearing potential must also have a negative serum pregnancy test.
• Patients must be able to understand and sign an informed consent form, which must comply with U.S. regulations (U.S. 21 Code of Federal Regulations (CFR) 50) and International Conference on Harmonisation (ICH) guidelines. Availability of alternative curative treatment must be fully explained to the patient and documented in the informed consent form.
• Eligible patients must meet the following laboratory parameters:
• White blood cell (WBC) \>3,000/mm3
• Platelets \>100,000/mm3
• Hct \>33% or Hgb \>10.5 gm/dL
• Prothrombin time (PT) within 3 seconds of control
• Serum creatinine \<1.5 mg/dL
• Serum calcium \<11.0 mg/dL
• Serum Amylase \< 2 times the upper limit of normal
• Negative HIV-Ag and HIV-Ab

You may not qualify if:

• Patients who have undergone previous treatment with a biological response modifier (interferons, interleukins) or prior immunotherapy within four (4) weeks of study enrollment.
• Patients currently requiring corticosteroids, under immune suppression for any reason including an organ allograft.
• Patients with known contraindications to analgesia or endoscopy.
• Patients with unstable cardiovascular disease (Class IV cardiovascular disease according to the New York Heart Association's functional criteria).
• Patients with any acute or chronic illness as judged clinically significant by the Investigators.
• Patients who have received prior chemotherapy or radiation therapy to the thorax within four (4) weeks of enrollment.
• Prior surgery within 30 days of execution of the informed consent form.
• Persistent fever greater than 39 degrees Celsius unless clinical assessment attributes the etiology to be tumor.
• Primary malignancy (present or remote) of sites other than the pancreas, except for the basal cell epithelioma of the skin.
• Use of investigational drugs within 30 days of execution of the informed consent form.
• Clinically significant (symptomatic) third space fluid collection (i.e.: ascites, pleural effusion).
• Patients with a diagnosis of an autoimmune state, or any psychiatric illness that in the opinion of the Investigators would compromise treatment.

Sponsors & Collaborators

• Edward Nelson: lead

Study Sites (1)

Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Edward L Nelson, M.D.

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. Edward Nelson

Study Record Dates

• First Submitted: January 17, 2008
• First Posted: January 24, 2008
• Study Start: June 1, 2004
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: June 11, 2018

Record last verified: 2018-06

Locations

US (1)