ECI301 and Radiation for Advanced or Metastatic Cancer

NCT ID: NCT01441115

Last Updated: 2021-12-28

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-09-06

Study Completion Date

2013-04-24

Brief Summary

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Background:

\- ECI301 is a drug that may help make cancer cells more visible to the immune system after radiation. The drug may also help the immune system destroy the cancer at sites that have not received radiation therapy. Researchers want to study ECI301 in people with advanced cancer or cancer that has spread in the body (metastatic).

Objectives:

\- To test ECI301 with radiation therapy for advanced or metastatic cancer.

Eligibility:

\- People at least 18 years of age with either metastatic or advanced cancer that may benefit from radiation therapy.

Design:

* Participants will be screened with a medical history and physical exam. They will also have blood and urine tests, and imaging studies.
* All participants will have radiation therapy 5 days a week for 2 weeks.
* They will have different doses of ECI301 to test its safety and effectiveness. ECI301 will be given in a vein during the second week of radiation therapy. Frequent blood tests and imaging studies will monitor the treatment.
* After participants have ECI301, tumor samples may be taken from the site that had radiation and another site that did not have radiation.
* Follow-up visits will include blood tests and imaging studies.

Detailed Description

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Background:

* Patients with metastatic or locally advanced cancer frequently require palliative radiotherapy to relieve symptoms; however, progression of disease is frequent in patients with extended survival
* Radiation results in tumor cell death which can result in increased dendritic cell activation and trafficking
* ECI301 is a derivative of Macrophage Inflammatory Protein-1 alpha, a 70 amino acid chemokine that is a ligand for C-C chemokine receptor type 1 (CCR1) and C-C chemokine receptor type 5 (CCR5), the chemokine receptors of immature dendritic cells.
* ECI301 has been shown to enhance the effect of radiotherapy in animal models.

Objectives:

* The primary objective is to determine the maximum tolerated dose (MTD) of ECI301 delivered in combination with 30 Gray (Gy) of external beam radiation to patients with metastatic or locally advanced cancer.
* The secondary objectives are:

* To describe the safety and tolerability of ECI301 delivered in combination with 30 Gy of external beam radiation to patients with metastatic or locally advanced cancer
* To evaluate the humoral and cellular immune responses by:

* Measurement of circulating precursor dendritic cells before and after the completion of ECI301
* Measurement of circulating MIP-alpha before and after the completion of ECI301
* Assessment of T-lymphocyte quantitative and qualitative changes by flow cytometry and assays for interferon (IFN-gamma) production
* To define pharmacologic parameters following the intravenous dose of ECI301
* To determine if neutralizing anti-EC301 antibodies occur after treatment
* To describe the response at the radiated site and distant sites after radiation in combination with ECI301

Eligibility:

* Age \>18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status \<2.
* Life expectancy of greater than 3 months
* Histologically confirmed metastatic or locally advanced cancer for which radiotherapeutic management would be appropriate
* No recent history of myocardial infarction or unstable angina

Design:

* This is a Phase I trial to determine the maximum tolerated dose of ECI301 in combination with external beam radiation therapy in patients with locally advanced or metastatic solid tumors.
* Patients will be treated with radiation therapy in a standard manner with ECI301 given daily during radiation. The dose of ECI301 will be escalated over the course of the trial to determine the maximum tolerated dose (MTD of daily ECI301 in combination with radiotherapy.
* We anticipate that accrual to this trial of 30 patients will take approximately 2 years.

Conditions

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Cancer Neoplasm Metastasis Radiation Oncology Neoplasm Metastasis

Keywords

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Metastasis Cancer Radiation Therapy Locally Advanced Palliation Metastatic Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ECI301 Dose level 1 - 25 ug/kg and Radiation for Advanced or Metastatic Cancer

ECI301 Dose level 1 - 25 ug/kg and Radiation for Advanced or Metastatic Cancer

Group Type EXPERIMENTAL

Radiation Therapy

Intervention Type PROCEDURE

ECI301

Intervention Type DRUG

Interventions

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Radiation Therapy

Intervention Type PROCEDURE

ECI301

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

2.1.1.1 Age greater than or equal to18 years.

2.1.1.2 Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.

2.1.1.3 Life expectancy of greater than 3 months

2.1.1.4 Histologically confirmed cancer

2.1.1.5 Extracranial metastatic cancer or locally advanced cancer for which palliative radiotherapeutic management would be appropriate (no more than two sites will be treated on this trial)

2.1.1.6 Patients must have measurable or evaluable disease at the site(s) requiring radiation

2.1.1.7 Adequate marrow and organ function defined as

* absolute neutrophil count (ANC) \> 1.5 times 10(9)/L,
* platelet count \> 100 times 10(9),
* hemoglobin \>9 g/L.
* creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal
* serum bilirubin \<1.5 times upper limit reference range (ULRR),
* alanine aminotransferase (ALT), aspartate aminotransferase (AST), or

alkaline phosphatase (ALP) \<2.5 times the ULRR (\<5 times the ULRR in the presence

of liver metastases)

2.1.1.8 Female patients of childbearing potential must either be surgically sterile to prevent pregnancy, be at least 1-year post-menopausal, or have had no menses for 12 months, or agree to use reliable methods of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, copper banded intrauterine device, tubal ligation or abstinence) from time of screening until 4 weeks after discontinuing study treatment. It is not known whether ECI301 has the capacity to induce hepatic enzymes so hormonal contraceptives should be combined with a barrier method of contraception.

2.1.1.9 Male patients must agree to use barrier contraception (i.e. condoms) and refrain from donating sperm from the start of dosing until 16 weeks after discontinuing study treatment. If male patients wish to father children, they should be advised to arrange for freezing of sperm prior to the start of study treatment.

Exclusion Criteria

2.1.2.1 Pregnant or lactating females

2.1.2.2 Contraindications to radiotherapy (i.e. prior radiotherapy to the intended treatment site)

2.1.2.3 Untreated or previously treated but progressive intracranial metastases (Patients with previously treated intracranial metastases should have no clinical evidence of progression and be at least 4 weeks from therapy for intracranial metastases)

2.1.2.4 Need for emergent radiotherapy (defined as need for radiotherapy within 24 hours of consultation at the judgment of the treating radiation oncologist)

2.1.2.5 Active treatment with immunosuppressive therapy and subjects taking systemic corticosteroid therapy for any reason including replacement therapy for hypoadrenalism

2.1.2.6 Chemotherapy, radiation therapy, Tamoxifen or investigational therapy during the 4 weeks prior to initiation of protocol therapy

2.1.2.7 History of rheumatoid arthritis, systemic lupus erythematosus, Sjogren's disease, sarcoidosis, vasculitis, polymyositis, temporal arteritis or any other autoimmune disease

2.1.2.8 History of organ transplant

2.1.2.9 Human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C positivity

2.1.2.10 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

2.1.2.11 Use of excluded immune modulating medications within 4 weeks prior to protocol therapy, or requirement for concurrent use.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Deborah Citrin, M.D.

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Deborah E Citrin, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

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National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Site Status

Countries

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United States

References

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Friedman EJ. Immune modulation by ionizing radiation and its implications for cancer immunotherapy. Curr Pharm Des. 2002;8(19):1765-80. doi: 10.2174/1381612023394089.

Reference Type BACKGROUND
PMID: 12171547 (View on PubMed)

Sharp HJ, Wansley EK, Garnett CT, Chakraborty M, Camphausen K, Schlom J, Hodge JW. Synergistic antitumor activity of immune strategies combined with radiation. Front Biosci. 2007 Sep 1;12:4900-10. doi: 10.2741/2436.

Reference Type BACKGROUND
PMID: 17569618 (View on PubMed)

Maurer M, von Stebut E. Macrophage inflammatory protein-1. Int J Biochem Cell Biol. 2004 Oct;36(10):1882-6. doi: 10.1016/j.biocel.2003.10.019.

Reference Type BACKGROUND
PMID: 15203102 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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11-C-0248

Identifier Type: -

Identifier Source: secondary_id

110248

Identifier Type: -

Identifier Source: org_study_id