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ECI301 and Radiation for Advanced or Metastatic Cancer

This study has been terminated.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01441115
First received: September 24, 2011
Last updated: February 19, 2014
Last verified: April 2013
  Purpose

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.
  • Followup visits will include blood tests and imaging studies....

Condition Intervention Phase
Cancer
Neoplasm Metastasis
Radiation Oncology
Neoplasm
Metastasis
Procedure: Radiation Therapy
Drug: ECI301
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of ECI301 in Combination With Radiation in Patients With Advanced or Metastatic Cancer

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Determine maximum tolerated dose (MTD) of ECI301 delivered in combination with 30 Gy external beam radiation to patients with metastatic or locally advanced cancer. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine safety & amp; tolerability of ECI301 in combination with radiation. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Evaluate the humoral and cellular immune responses. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Define pharmacologic parameters [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Describe the response at the radiated site and distant. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: September 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Radiation Therapy
    N/A
    Drug: ECI301
    N/A
Detailed Description:

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?, a 70 amino acid chemokine that is a ligand for CCR1 and 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 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-? before and after the completion of ECI301
      • Assessment of T-lymphocyte quantitative and qualitative changes by flow cytometry and assays for IFN? 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.
  • 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 MTD of daily ECI301 in combination with radiotherapy.
  • We anticipate that accrual to this trial of 30 patients will take approximately 2 years.
  Eligibility

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

2.1.1.1 Age greater than or equal to18 years.

2.1.1.2 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 child bearing 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, Sj(SqrRoot)(Delta)grens disease, sarcoidosis, vasculitis, polymyositis, temporal arteritis or any other autoimmune disease

2.1.2.8 History of organ transplant

2.1.2.9 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.

  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: NCT01441115

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Deborah E Citrin, M.D. National Cancer Institute (NCI)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01441115     History of Changes
Other Study ID Numbers: 110248, 11-C-0248
Study First Received: September 24, 2011
Last Updated: February 19, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Metastasis
Cancer
Radiation Therapy
Locally Advanced
Palliation
Metastatic Cancer

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Neoplastic Processes
Pathologic Processes

ClinicalTrials.gov processed this record on November 20, 2014