A Study of Neoadjuvant Photodynamic Immunomodulation for Colon Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by Holcombe, Randall F., M.D..
Recruitment status was  Recruiting
Sponsor:
Collaborators:
University of California, Irvine
Information provided by (Responsible Party):
Holcombe, Randall F., M.D.
ClinicalTrials.gov Identifier:
NCT01522677
First received: January 26, 2012
Last updated: January 31, 2012
Last verified: January 2012
  Purpose

The central hypothesis for this study is that it is safe and feasible to administer intraluminal photodynamic therapy (PDT) to colon cancers by colonoscopy to induce localized inflammatory/immune response. The objective is to demonstrate the feasibility and safety of PDT to colon cancer patients administered before surgery and to characterize the inflammatory/immune response at the tumor site and systemically. The long-term objective of these studies is to modify he natural biology of colorectal cancers and improve patient survival.


Condition Intervention Phase
Colon Cancer
Drug: PDT with 5-ALA radiosensitization
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Neoadjuvant Photodynamic Immunomodulation for Colon Cancer

Resource links provided by NLM:


Further study details as provided by Holcombe, Randall F., M.D.:

Primary Outcome Measures:
  • Efficacy [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Define biologic efficacy of PDT in relation to generation of an immune response at the tumor site and systemically. This will be measured by degree of dendritic cell infiltration into tumor and regional lymph nodes, and degree of systemic immunity directed against colon cancer antigens immedicately post procedure and after 6 months.

  • Safety [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Safety will be evaluated from enrollment through 6 months. This will be measured by proportion of patients completing planned surgery, proportion of patients experiencing grade 3 or 4 toxicities, and lack of observation of serious adverse events related to the study procedure.


Secondary Outcome Measures:
  • Quality of Life [ Time Frame: 6 months after completion of participation ] [ Designated as safety issue: No ]
    Quality of life will be evaluated 6 months following completion of participation in the study

  • Sustained immunity [ Time Frame: 1.5-6 months post completion of participation ] [ Designated as safety issue: No ]
    Immunologic parameters will be monitored following completion of the study as a measure of sustained immunity


Estimated Enrollment: 42
Study Start Date: January 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PDT
Participants receive neoadjuvant 5-ALA and PDT.
Drug: PDT with 5-ALA radiosensitization
Patients receive neoadjuvant PDT with radiosensitizing 5-ALA 4 days prior to surgery for colon cancer.
Other Names:
  • Photodynamic therapy
  • 5-ALA

Detailed Description:

The central hypothesis for this study is that it is safe and feasible to administer intraluminal photodynamic therapy (PDT) to colon cancers, via colonoscopy, in the neoadjuvant setting to induce localized tumor cell death and an inflammatory/immune response with an increased Th1 component, utilizing 5-ALA as a photosensitizer. The objective is to conduct an initial phase I/II clinical study to demonstrate the feasibility and safety of colonoscopic, neoadjuvant intraluminal PDT to colon cancer patients administered 96 hours pre-resection, to characterize the inflammatory/immune response at the PDT treated tumor site, and to evaluate the systemic anti-tumor immune response. The long-term objective of these studies is to provide an easily administered, adjunctive, therapeutic maneuver that lacks systemic toxicity, with the potential to modulate the natural biology of colorectal cancers that have not elicited a favorable anti-tumor immune response and to improve patient survival.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have a histologically proven diagnosis of colorectal cancer.
  2. Have clinical stage I, II, or III disease.
  3. Expected survival must be greater than twelve (12) months.
  4. A Karnofsky Performance Status (KPS) must be 70 or greater (Appendix I).
  5. Patients must be >21 years of age.
  6. No prior therapy.
  7. Female patients must 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.
  8. Patients must be able to understand and sign an informed consent form, which must comply with U.S. regulations (U.S. 21 CFR 50) and ICH guidelines.
  9. Eligible patients must have adequate initial hematologic and coagulation parameters, hemoglobin ≥ 11g/dl, platelet count >50,000, Protime and Prothrombin Time ≤ 1.5 x normal.
  10. Eligible patients must have adequate bone marrow, liver and renal function: ANC > 1500/μL, Platelets >100,000 x μL, total bilirubin < the upper limit of normal (ULN), and creatinine clearance (CrCl) > 45 mL/min

Exclusion Criteria:

  1. Any co-morbidity that precludes primary surgical resection of the colorectal tumor.
  2. Any significant general organ system compromise including:

    • Liver function, transaminases ≥ 2 x,
    • Renal function, Cr ≥ 1.5 x upper limit of normal
    • Pulmonary function, room air O2 saturation <90%
    • Cardiovascular function, Patients with significant (Class III or IV) cardiovascular disease according to the New York Heart Association's functional criteria (Appendix II)
    • Gastrointestinal function, i.e. active inflammatory bowel disease or active peptic ulcer disease.
  3. Any contraindication to repeat colonoscopy, such as idiosyncratic reactivity to conscious sedation medications.
  4. Prior treatment for the diagnosis of colorectal cancer, including surgical resection.
  5. Stage IV colorectal cancer, i.e. the clinical presence of metastases
  6. Prior malignant diagnosis except for the basal cell epithelioma of the skin.
  7. Persistent fever greater than 38 C.
  8. Mineral overload syndromes for Lead, Zinc, Copper or Iron.
  9. Use of any agent that modulates 5-ALA metabolism and porphyrin synthesis, e.g. St. John's Wort.
  10. Required use of corticosteroids or immune suppression for any reason including an organ allograft or HIV infection
  11. Patients with any acute or chronic illness including cardiovascular disease (e.g. history of atrial fibrillation or ventricular arrhythmias) or history of myocardial infarction, autoimmune state, or any psychiatric illness that in the opinion of the Investigators would compromise treatment.
  12. Use of investigational drugs within 30 days of execution of the informed consent form.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01522677

Contacts
Contact: Randall F Holcombe, MD 2126595420 randall.holcombe@mssm.edu
Contact: Edward L Nelson, MD 7144565153 enelson@uci.edu

Locations
United States, California
University of California, Irvine Recruiting
Orange, California, United States, 92868
Contact: Edward L Nelson, MD    714-456-5153    enelson@uci.edu   
Principal Investigator: Edward L Nelson, MD         
United States, New York
Mounst Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Contact: Randall F Holcombe, MD    212-659-5420    randall.holcombe@mssm.edu   
Contact: Kiev Gimpel-Tetra, RN    2128247117    kiev.gimpel-tetra@mssm.edu   
Principal Investigator: Randall F Holcombe, MD         
Sponsors and Collaborators
Holcombe, Randall F., M.D.
University of California, Irvine
Investigators
Principal Investigator: Randall F Holcombe, MD Mount Sinai School of Medicine
Principal Investigator: Edward L Nelson, MD University of California, Irvine
  More Information

No publications provided

Responsible Party: Holcombe, Randall F., M.D.
ClinicalTrials.gov Identifier: NCT01522677     History of Changes
Other Study ID Numbers: 108643, 1R21CA153594
Study First Received: January 26, 2012
Last Updated: January 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Holcombe, Randall F., M.D.:
tumor immunology
neoadjuvant
colonoscopy
photosensitization

Additional relevant MeSH terms:
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Colonic Diseases
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on July 24, 2014