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A Study of Neoadjuvant Photodynamic Immunomodulation for Colon Cancer

Primary Purpose

Colon Cancer

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

PDT with 5-ALA radiosensitization

About this trial

This is an interventional treatment trial for Colon Cancer focused on measuring tumor immunology, neoadjuvant, colonoscopy, photosensitization

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
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.
Use of investigational drugs within 30 days of execution of the informed consent form.

Sites / Locations

University of California, Irvine
Mounst Sinai School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PDT

Arm Description

Participants receive neoadjuvant 5-ALA and PDT.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Quality of Life

Quality of life will be evaluated 6 months following completion of participation in the study

Sustained immunity

Immunologic parameters will be monitored following completion of the study as a measure of sustained immunity

Full Information

NCT ID

NCT01522677

First Posted

January 26, 2012

Last Updated

November 30, 2016

Sponsor

Edward Nelson

Collaborators

University of California, Irvine, National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01522677

Brief Title

A Study of Neoadjuvant Photodynamic Immunomodulation for Colon Cancer

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Withdrawn

Why Stopped

Slow accrual

Study Start Date

August 2012 (undefined)

Primary Completion Date

May 2014 (Actual)

Study Completion Date

May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Edward Nelson

Collaborators

University of California, Irvine, National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colon Cancer

Keywords

tumor immunology, neoadjuvant, colonoscopy, photosensitization

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PDT

Arm Type

Experimental

Arm Description

Participants receive neoadjuvant 5-ALA and PDT.

Intervention Type

Drug

Intervention Name(s)

PDT with 5-ALA radiosensitization

Other Intervention Name(s)

Photodynamic therapy, 5-ALA

Intervention Description

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

Primary Outcome Measure Information:

Title

Efficacy

Description

Time Frame

6 months

Title

Safety

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Quality of Life

Description

Quality of life will be evaluated 6 months following completion of participation in the study

Time Frame

6 months after completion of participation

Title

Sustained immunity

Description

Immunologic parameters will be monitored following completion of the study as a measure of sustained immunity

Time Frame

1.5-6 months post completion of participation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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 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. Use of investigational drugs within 30 days of execution of the informed consent form.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Randall F Holcombe, MD

Organizational Affiliation

Icahn School of Medicine at Mount Sinai

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Edward L Nelson, MD

Organizational Affiliation

University of California, Irvine

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California, Irvine

City

Orange

State/Province

California

ZIP/Postal Code

92868

Country

United States

Facility Name

Mounst Sinai School of Medicine

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

12. IPD Sharing Statement

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A Study of Neoadjuvant Photodynamic Immunomodulation for Colon Cancer

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