A Study of Neoadjuvant Photodynamic Immunomodulation for Colon Cancer

NCT01522677 | Withdrawn Phase 1 DMC

• 2 other identifiers: UCI 10-261R21CA153594
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Colon Cancer

Keywords

tumor immunology; neoadjuvant; colonoscopy; photosensitization

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Quality of Life

  6 months after completion of participation

• Sustained immunity

  1.5-6 months post completion of participation

Study Arms (1)

PDT

EXPERIMENTAL

Participants receive neoadjuvant 5-ALA and PDT.

Drug: PDT with 5-ALA radiosensitization

Interventions

PDT with 5-ALA radiosensitization DRUG

Patients receive neoadjuvant PDT with radiosensitizing 5-ALA 4 days prior to surgery for colon cancer.

Also known as: Photodynamic therapy, 5-ALA

PDT

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 a histologically proven diagnosis of colorectal cancer.
• Have clinical stage I, II, or III disease.
• Expected survival must be greater than twelve (12) months.
• A Karnofsky Performance Status (KPS) must be 70 or greater (Appendix I).
• Patients must be \>21 years of age.
• No prior therapy.
• 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.
• 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.
• 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.
• 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

You may not qualify if:

• Any co-morbidity that precludes primary surgical resection of the colorectal tumor.
• 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.
• Any contraindication to repeat colonoscopy, such as idiosyncratic reactivity to conscious sedation medications.
• Prior treatment for the diagnosis of colorectal cancer, including surgical resection.
• Stage IV colorectal cancer, i.e. the clinical presence of metastases
• Prior malignant diagnosis except for the basal cell epithelioma of the skin.
• Persistent fever greater than 38 C.
• Mineral overload syndromes for Lead, Zinc, Copper or Iron.
• Use of any agent that modulates 5-ALA metabolism and porphyrin synthesis, e.g. St. John's Wort.
• Required use of corticosteroids or immune suppression for any reason including an organ allograft or HIV infection

Sponsors & Collaborators

• Edward Nelson: lead
• University of California, Irvine: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of California, Irvine

Orange, California, 92868, United States

Location

Mounst Sinai School of Medicine

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Photosensitivity Disorders

Interventions

1-phenyl-3,3-dimethyltriazene; Photochemotherapy

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; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Phototherapy

Study Officials

• Randall F Holcombe, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Edward L Nelson, MD

  University of California, Irvine

  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 26, 2012
• First Posted: January 31, 2012
• Study Start: August 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: December 1, 2016

Record last verified: 2016-11

Locations

US (2)