ECI301 and Radiation for Advanced or Metastatic Cancer

Phase 1

Terminated

Conditions: Metastasis
Cancer
Neoplasm Metastasis
Radiation Oncology
Neoplasm

Interventions: Procedure: Radiation Therapy
Drug: ECI301

Registration Number: NCT01441115

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 2

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) of ECI301 Delivered in Combination With 30 Gray (Gy) External Beam Radiation to Participants With Metastatic or Locally Advanced Cancer	During treatment or the first three weeks after treatment	MTD is defined as the highest dose level at which no more than 1 of 6 participants experience dose-limiting toxicity (DLT) during treatment or the first three weeks after treatment, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. Examples of DLT is any grade 3 or greater non-hematologic toxicity, ang grade 3 neutropenia or thrombocytopenia, any grade 4 anemia, and toxicity requiring a cumulative radiation treatment delay of 4 or more days.

Secondary Outcome Measures

Name	Time	Method
Pharmacologic Parameters Following the Intravenous Dose of ECI301	Following the intravenous dose of ECI301	Pharmacologic parameters will be derived using non-compartmental analysis.
Number of Participants With Response at the Radiated Site and Distant Site After Radiation in Combination With ECI301	6 months	Response will be measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progression. Stable disease is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Number of Adverse Events Unrelated, Unlikely, and Possibly Related to ECI301 Delivered in Combination With 30 Gray (Gy) of External Beam Radiation to Participants With Metastatic or Locally Advanced Cancer	Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 5 months and 25 days.	Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) and the Radiation Therapy Oncology Group (RTOG) criteria.
Humoral and Cellular Immune Responses	Before and after completion of ECI301	Measurement of circulating precursor dendritic cells, circulating macrophage inflammatory protein-1 alpha (MIP-α), and assessment of T-lymphocytes will be measured by flow cytometry and assays for type II interferon (IFNγ) production.