An Open Label Phase I Study to Eval the Safety and Tolerability of a Vaccine (GI-6207) Consisting of Whole, Heat-killed Recombinant Saccharomyces Cerevisiae (Yeast) Genetically Modified to Express CEA Protein in Adults With Metastatic CEA-expressing ...

NCT00924092 | Completed Phase 1

• 2 other identifiers: 09010109-C-0101
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Objectives:

• To find out the maximum tolerated dose of the GI-6207 vaccine (the highest dose that does not cause unacceptable side effects), and to evaluate any side effects.
• To see if GI-6207 has any effect on patients tumors.
• To learn how the vaccine causes immune responses against the cancer. Eligibility:
• Patients 18 years of age and older who have been diagnosed with a cancer that has not responded to standard treatments. Patients must not be allergic to yeast or yeast products. Design:
• Initial physical examination, blood and tissue sampling, computed tomography (CT) scan, and skin test to determine eligibility for the procedure.
• Treatment with GI-6027 in seven 14-day cycles as follows:
• Vaccine administered on days 1, 15, 29, 43, 57, 71, and 85.
• Vaccine given at four sites around the body: right and left chest area below the armpit, and right and left upper thigh in the pelvic region. (These areas drain into parts of your body that contain large numbers of lymph nodes. The lymph nodes contain immune cells that may be activated by the vaccine to target cancer cells.)
• Clinic visits for physical examinations to check vital signs, take additional blood and urine samples, and perform other tests needed for the study.
• After day 85 (about 3 months), patients will continue to receive vaccine monthly (or every 28 days) as long as the vaccine is not producing harmful effects or side effects and the cancer is either stable or reducing. Patients who do well on the vaccine may continue to receive it for as long as it is available.

Conditions

Prostate Cancer; Breast Cancer; Lung Cancer; Colorectal Cancer; Head and Neck Cancer

Keywords

Immunotherapy; Lung Cancer; Colorectal Cancer; Head and Neck Cancer; Prostate; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• To determine the safety and tolerability of escalating doses of a heated-killed yeast-based vaccine that targets tumors that express CEA.

Secondary Outcomes (1)

• To evaluate CD4 and CD8 immunologic response. To evaluate humoral immune response to yeast antigen. To evaluate evidence of clinical benefit such as PFS, OR, & decreases in circulating tumor cells & tumor markers.

Interventions

GI-6207 [Recombinant Saccharomyces Cerevisia BIOLOGICAL

(Yeast CEA Vaccine)(GI-6207[Recombinant Sarrcharomyces Cerevusua-CEA (610D)]) DRUG

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. Histologically confirmed carcinoma by the NIH Laboratory of Pathology that has been shown to express CEA (either a CEA serum level \> 5 microg/L or a tumor that stains positive for CEA in \> 20% of a tumor block).
• B. Completed or had disease progression on at least one prior line of disease-appropriate therapy for metastatic disease, or not be a candidate for therapy of proven efficacy for their disease.
• C. 18 years of age or greater.
• D. Must have metastatic disease that is measurable or non-measurable but evaluable (e.g., pleural effusion or present on bone scan).
• E. Ability to understand and the willingness to sign a written informed consent document.
• F. ECOG performance status of 0 2 (Karnofsky greater than or equal to 50).
• G. Serum creatinine less than or equal to 1.5 times upper limit of normal OR creatinine clearance on a 24-h urine collection of greater than or equal to 60 mL/min.
• H. ALT and AST less than or equal to 2.5 times the upper limits of normal.
• I. Total bilirubin less than or equal to 1.5 times upper limit of normal OR in patients with Gilbert s syndrome, a total bilirubin less than or equal to 3.0.
• J. Recovered completely from any reversible toxicity associated with recent therapy. Typically this is 3 4 weeks for patients who most recently received cytotoxic therapy, except for the nitrosoureas and mitomycin C for which 6 weeks is needed for recovery. There should be a minimum of 2 weeks from any prior chemotherapy, immunotherapy and/or radiation.
• K. Hematological eligibility parameters (within 16 days of starting therapy):
• Granulocyte count greater than or equal to 1,500/mm(3)
• Platelet count greater than or equal to 100,000/mm(3)
• L. Prior immune therapy (e.g. related vaccinia and fowlpox vaccines or antigen-specific peptides) is allowed.
• M. Men and women must agree to use effective birth control or abstinence during and for a period of 4 months after the last vaccination therapy.

You may not qualify if:

• A. Patients should have no evidence of immune dysfunction as listed below.
• Human immunodeficiency virus positivity due to the potential for decreased immune response to the vaccine.
• Active autoimmune diseases requiring treatment or a history of autoimmune disease that might be stimulated by vaccine treatment. This requirement is due to the potential risks of exacerbating autoimmunity. Patients with endocrine autoimmune disease that is controlled by replacement therapy, including thyroid disease and adrenal disease; or those with vitiligo, may be enrolled.
• Concurrent use of systemic steroids, except for physiologic doses for systemic steroid replacement or local (topical, nasal, or inhaled) steroid use. Limited doses of systemic steroids to prevent IV contrast, allergic reaction, or anaphylaxis (in patients who have known contrast allergies) are allowed.
• B. History of allergy or untoward reaction to yeast-based products (any hypersensitivity to yeast-based products will be excluded).
• C. Pregnant or breast-feeding women.
• E. Serious intercurrent medical illness which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis.
• F. Untreated brain metastases (or local treatment of brain metastases within the last 6 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic toxicities.
• G. Concurrent chemotherapy. An exception is to allow for patients on the extension phase only with breast cancer who are receiving trastuzumab to continue therapy with trastuzumab while receiving the vaccine treatment.
• K. Chronic hepatitis infection, including B and C, because of potential immune impairment.
• L. Patients requiring continuous tricyclic antidepressant therapy should be excluded due to the interference with the yeast skin test in creating false negative test results.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Robbins PF, Eggensperger D, Qi CF, Schlom J. Definition of the expression of the human carcinoembryonic antigen and non-specific cross-reacting antigen in human breast and lung carcinomas. Int J Cancer. 1993 Apr 1;53(6):892-7. doi: 10.1002/ijc.2910530604.

  PMID: 8386136 BACKGROUND

• Kass ES, Greiner JW, Kantor JA, Tsang KY, Guadagni F, Chen Z, Clark B, De Pascalis R, Schlom J, Van Waes C. Carcinoembryonic antigen as a target for specific antitumor immunotherapy of head and neck cancer. Cancer Res. 2002 Sep 1;62(17):5049-57.

  PMID: 12208760 BACKGROUND

• Hodge JW, Tsang KY, Poole DJ, Schlom J. General keynote: vaccine strategies for the therapy of ovarian cancer. Gynecol Oncol. 2003 Jan;88(1 Pt 2):S97-104; discussion S110-3. doi: 10.1006/gyno.2002.6694. No abstract available.

  PMID: 12586096 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms; Breast Neoplasms; Lung Neoplasms; Colorectal Neoplasms; Head and Neck Neoplasms

Interventions

yeast-CEA vaccine

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Ravi A Madan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: March 13, 2009
• Study Completion: August 2, 2012
• Last Updated: December 12, 2019

Record last verified: 2014-05-20

Locations

US (1)