Phase I Study of Ad5-hGCC (Human Guanylyl Cyclase C)-PADRE in Stage I/II Colon Cancer

NCT01972737 | Completed Phase 1 DMC

• 3 other identifiers: 13S.462SAP #4100051723JT 2657
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety, tolerability and ability to stimulate hGCC-specific antibody and killer T cell immune responses of an Ad5-hGCC-PADRE vaccine in stage I and stage II Caucasian and African American colon cancer patients.

Conditions

Colon Cancer

Keywords

Vaccine; Colon cancer; safety; tolerability; antibody responses; T cell responses

Outcome Measures

Primary Outcomes (2)

• Adverse events

  Quantify treatment-emergent and related acute and sub-acute adverse events, serious adverse events, and Grade 3 and 4 non-laboratory abnormalities for safety assessments during the 6-month period after the injection of Ad5-hGCC-PADRE.

  Continuous for 6 months after vaccination.

• Antibody responses

  Determine whether Ad5-hGCC-PADRE induces an antibody response to GCC at 1 month following vaccination with Ad5-hGCC-PADRE.

  One month following vaccination.

Secondary Outcomes (2)

• T cell responses

  One month following vaccination.

• Persistent immunological responses

  Three and six months after vaccination.

Other Outcomes (3)

• Occult metastases and immune responses

  One, three, and six months following vaccination.

• Race and immune responses

  One, three and six months following vaccination.

• Time to recurrence and disease-free survival and immune responses

  Annually for 5 years from the time of vaccination

Study Arms (1)

Ad5-hGCC-PADRE Vaccine

EXPERIMENTAL

Active vaccine

Biological: Ad5-hGCC-PADRE vaccine

Interventions

Ad5-hGCC-PADRE vaccine BIOLOGICAL

A single intramuscular dose (100 billion virus particles) of Ad5-hGCC-PADRE vaccine.

Ad5-hGCC-PADRE Vaccine

Eligibility Criteria

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

You may qualify if:

• Male and Female African American or Caucasian subjects older than 18 years of age. Race will be defined by the subject.
• Stage I or stage II (pN0) colon cancer within 3 years of surgery
• Competent immune system, defined by the ability to make a delayed type hypersensitivity (DTH) reaction to at least one of the following: candida, mumps, tetanus or trichophyton
• Adequate renal, liver, and bone marrow functions:
• Serum creatinine ≤ 2.0 mg/dl, Hemoglobin ≥ 10.0 g/dl WBC (white blood cells) ≥ 3,000 /mm3, platelet count ≥ 100,000/mm3, total bilirubin ≤2.0 mg/ml, and albumin ≥ 3.0 g/dl
• Lymph node specimens available for quantification of occult metastases
• Minimum of 2 months and maximum of 36 months since surgery
• No clinical or laboratory evidence of local or systemic recurrence at entry to the study
• Expected survival of at least 6 months
• Karnofsky performance status ≥ 80 (ECOG 0 or 1)
• Willingness and ability to understand and give informed consent and follow the procedures described in the protocol

You may not qualify if:

• Rectal cancer
• Prior chemotherapy/radiotherapy/immunotherapy/experimental medications for colon cancer
• Prior splenectomy
• Concurrent use of systemic steroids or immunosuppressive drugs (Note: topical or inhaled aerosol steroid therapies are not contraindicated for participation in the study)
• HIV-positive by ELISA, confirmed by Western blot
• Active autoimmune diseases that the Investigator considers would interfere with an immunologic response (e.g., systemic lupus erythematosus, multiple sclerosis or ankylosing spondylitis)
• Other malignancy within 5 years except curatively treated non-melanomatous skin cancer and curatively treated carcinoma in situ of the uterine cervix, or early stage (stage A or B1) prostate cancer
• Medically-proven inflammatory bowel disease
• Has at the time of enrollment, serious infection or other serious medical condition that implies a survival of less than six months
• Pregnancy or lactation (serum B-human chorionic gonadotropin test must be negative in fertile women at screening visit). Subjects will be asked to use contraception during conduct of the study.
• Past medical history of serious reaction to adenovirus vaccine
• Mental handicap
• Chronic diarrhea \>6 times per day

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (8)

• Waldman SA, Hyslop T, Schulz S, Barkun A, Nielsen K, Haaf J, Bonaccorso C, Li Y, Weinberg DS. Association of GUCY2C expression in lymph nodes with time to recurrence and disease-free survival in pN0 colorectal cancer. JAMA. 2009 Feb 18;301(7):745-52. doi: 10.1001/jama.2009.141.

  PMID: 19224751 BACKGROUND

• Snook AE, Magee MS, Marszalowicz GP, Schulz S, Waldman SA. Epitope-targeted cytotoxic T cells mediate lineage-specific antitumor efficacy induced by the cancer mucosa antigen GUCY2C. Cancer Immunol Immunother. 2012 May;61(5):713-23. doi: 10.1007/s00262-011-1133-0. Epub 2011 Nov 6.

  PMID: 22057677 BACKGROUND

• Snook AE, Li P, Stafford BJ, Faul EJ, Huang L, Birbe RC, Bombonati A, Schulz S, Schnell MJ, Eisenlohr LC, Waldman SA. Lineage-specific T-cell responses to cancer mucosa antigen oppose systemic metastases without mucosal inflammatory disease. Cancer Res. 2009 Apr 15;69(8):3537-44. doi: 10.1158/0008-5472.CAN-08-3386. Epub 2009 Apr 7.

  PMID: 19351847 BACKGROUND

• Snook AE, Huang L, Schulz S, Eisenlohr LC, Waldman SA. Cytokine adjuvanation of therapeutic anti-tumor immunity targeted to cancer mucosa antigens. Clin Transl Sci. 2008 Dec;1(3):263-4. doi: 10.1111/j.1752-8062.2008.00054.x.

  PMID: 19956776 BACKGROUND

• Snook AE, Stafford BJ, Eisenlohr LC, Rothstein JL, Waldman SA. Mucosally restricted antigens as novel immunological targets for antitumor therapy. Biomark Med. 2007 Jun;1(1):187-202. doi: 10.2217/17520363.1.1.187.

  PMID: 20477468 BACKGROUND

• Snook AE, Stafford BJ, Li P, Tan G, Huang L, Birbe R, Schulz S, Schnell MJ, Thakur M, Rothstein JL, Eisenlohr LC, Waldman SA. Guanylyl cyclase C-induced immunotherapeutic responses opposing tumor metastases without autoimmunity. J Natl Cancer Inst. 2008 Jul 2;100(13):950-61. doi: 10.1093/jnci/djn178. Epub 2008 Jun 24.

  PMID: 18577748 BACKGROUND

• Snook AE, Baybutt TR, Xiang B, Abraham TS, Flickinger JC Jr, Hyslop T, Zhan T, Kraft WK, Sato T, Waldman SA. Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients. J Immunother Cancer. 2019 Apr 23;7(1):104. doi: 10.1186/s40425-019-0576-2.

  PMID: 31010434 DERIVED

• Myers RE, Wolf T, Shwae P, Hegarty S, Peiper SC, Waldman SA. A survey of physician receptivity to molecular diagnostic testing and readiness to act on results for early-stage colon cancer patients. BMC Cancer. 2016 Oct 3;16(1):766. doi: 10.1186/s12885-016-2812-1.

  PMID: 27716119 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Scott A Waldman, MD, PhD

  Thomas Jefferson University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2013
• First Posted: October 30, 2013
• Study Start: October 1, 2013
• Primary Completion: June 3, 2014
• Study Completion: January 13, 2016
• Last Updated: May 2, 2025

Record last verified: 2025-05

Locations

US (1)