A Study of Neoadjuvant Photodynamic Immunomodulation for Colon Cancer

A Phase I/II Study of Neoadjuvant Photodynamic Immunomodulation for Colon Cancer

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.

Study Overview

• Status: Withdrawn
• Conditions: Colon Cancer
• Intervention / Treatment: Drug: PDT with 5-ALA radiosensitization

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • University of California, Irvine
  • New York
    • New York, New York, United States, 10029
      • Mounst Sinai School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: 5-ALA; Photodynamic therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	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 immediately post procedure and after 6 months.	6 months
Safety	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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life	Quality of life will be evaluated 6 months following completion of participation in the study	6 months after completion of participation
Sustained immunity	Immunologic parameters will be monitored following completion of the study as a measure of sustained immunity	1.5-6 months post completion of participation

Collaborators and Investigators

• Sponsor: Edward Nelson
• Collaborators: National Cancer Institute (NCI); University of California, Irvine
• Investigators: Principal Investigator: Edward L Nelson, MD, University of California, Irvine

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): May 1, 2014

Study Registration Dates

• First Submitted: January 26, 2012
• First Submitted That Met QC Criteria: January 30, 2012
• First Posted (ESTIMATE): January 31, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): December 1, 2016
• Last Update Submitted That Met QC Criteria: November 30, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: neoadjuvant; colonoscopy; tumor immunology; photosensitization
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid
• Other Study ID Numbers: UCI 10-26; 1R21CA153594 (NIH)