Immune Response and Safety of HS110 Vaccine in Combination With Erlotinib in Patients With Non-Small Cell Lung Cancer

November 20, 2013 updated by: Heat Biologics

A Phase 2A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Immune Response, Safety and Efficacy of HS-110 in Combination With Erlotinib vs. Erlotinib as a Single Agent in Patients With Advanced, Non-EGFR Mutated Non-Small Cell Lung Cancer (NSCLC)

This study will enroll patients with locally advanced or metastatic non-EGFR mutated Non-Small Cell Lung Cancer (NSCLC) lung cancer after failure of at least one but no more than two prior approved treatment regimens. Patients will be randomized to receive one of two doses of vaccine or placebo to be dosed twice weekly for 18 weeks (36 doses total) and patients will also receive erlotinib 150mg taken orally once daily for the duration of the trial. The study will examine the immune effects, safety and efficacy of two different doses of HS110 vaccine in combination with erlotinib versus erlotinib alone.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This multicenter, randomized, double-blind, placebo-controlled study will enroll patients with advanced NSCLC (squamous cell or non-squamous cell) without EGFR mutations (either L858R or 746-750 deletions) who have had progression or recurrence of their disease following at least one but no more than two prior regimens (adjuvant therapy excluded) of approved therapy that did not include immunomodulating or anti-EGFR targeted therapy for their disease. EFGR status must be known at the time of enrollment either via prior determination or testing performed from archival tissue during the screening process. Patients with resectable disease will eligible if resection can be deferred for the first six weeks of vaccine. Patients will receive twice weekly dosing of vaccine (spatially divided as 5 intradermal injections) for 18 weeks (36 total doses). Patients will be randomized in a 2:1 fashion; with 30 patients in each of the HS110 treatments groups (high and low dose) and 15 patients will receive placebo injections. Patients will also receive erlotinib 150mg once daily for the duration of the trial. A total of 75 patients will be enrolled in the trial. The study includes a lead-in phase of 9 patients (3 from each dosing group) who will be observed weekly for 4 weeks to assess the safety of combining HS110 with erlotinib. Treatment of the first 4 patients will be staggered by 2 week intervals to allow for safety evaluation before treating additional patients. If the combination of proves to be safe and well-tolerated in the first 9 patients, enrollment will be opened up to the predetermined sample size for each arm. A Data Monitoring Committee (DMC) will be used in this study to independently monitor adverse events and progression/survival data. The DMC will meet at the completion of the run-in period and after half the patients have been dosed through week 6 and week 12.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75201
        • Mary Crowley Cancer Research Centers

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Willing and able to comply with the protocol and sign informed consent.
  • Histologically or cytologically confirmed locally advanced or metastatic squamous cell or non-squamous cell NSCLC after at least one but no more than two prior regimens of approved therapy for their disease (not including adjuvant treatment).
  • Confirmation that their disease has no known EGFR mutations based on documented prior analysis or study-specific analysis of archival tumor tissue.
  • At least one site of bi-dimensionally measurable NSCLC disease.
  • Patients with recurrent, resectable disease able to undergo six weeks of vaccine therapy prior to resection.
  • Brain metastasis if present and treated must be stable by CT scn or MRI for at least 8 weeks.
  • Age ≥ 18 years.
  • EGOG performance status of 0-1.
  • Lab parameters
  • Albumin ≥ 3.5mg/dL
  • Total Bilirubin < 1.5mg/dL
  • Alanine transaminase (ALT), and aspartate transaminase(AST)≤ 2.5 x upper limits of normal or ≤ x ULN in case of liver metastases.
  • Serum creatinine < 1.5mg/dL or calculated creatinine clearance >50 mL/minute per the Cockcroft-Gault formula.

  • White blood cell (WBC) count ≥ 4,000/mm3 with an absolute neutrophil count

    • 1,500mm3.
  • Hemoglobin ≥ 9g/dL
  • Platelet count ≥ 100,000/mm3
  • Women of childbearing potential or men of fathering potential must use adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide or surgical sterilization) during the study and for 6 months after receiving the last administration of study medication. Female patients of childbearing potential must test negative for pregnancy prior to enrolling in the trial. Post-menopausal (cessation of menses for more than 6 months) women are eligible for this study.

Exclusion Criteria:

  • No prior therapy with EGFR-targeted drugs, including approved and investigational therapies, or prior immunologic or biologic response modifier therapy for treatment of their disease.
  • Uncontrolled or untreated brain or spinal cord metastases or meningeal carcinomatosis.
  • Known human immunodeficiency virus (HIV), hepatitis B or C, or severe/uncontrolled infections or intercurrent illness, unrelated to the tumor, requiring active therapy.
  • Autoimmunity syndromes (primary or acquired) including, but not limited to, the following: rheumatoid arthritis, systemic lupus erythematosus, Sjogren's disease, sarcoidosis, vasculitis, polymyositis, or glomerulonephritis requiring active steroid or other immunosuppressive therapy.
  • Known immunodeficiency disorders, either primary or acquired.
  • Other malignancies present within the past 3 years, except for cutaneous basal and/or squamous cell carcinoma(s) or in situ cervical cancer.
  • History of clinically significant cardiac impairment, congestive heart failure > New York Heart Association (NYHA) cardiac disease classification Class II, unstable angina, or myocardial infarction during the previous 6 months, or serious cardiac arrhythmia.
  • Known alcohol or chemical abuse, or mental or psychiatric condition precluding compliance with the protocol.
  • Chemotherapy, radiation, or other antitumor therapy during the last 4 weeks.
  • Pregnant, nursing, or planning a pregnancy (both men and women) within 12 months of enrollment.
  • Known allergy to soy or egg products.
  • Patient is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Low-dose HS-110
2,000,000 cells/0.5mls + erlotinib 150mg orally once daily
Biological: HS110 vaccine
0.5ml to be administered twice weekly for 18 weeks (36 doses)
Biological: HS110 vaccine
0.5 mls to be dosed twice weekly for 18 weeks (36 doses)
Experimental: High dose HS110
10,000,000 HS110 cells/0.5ml + erlotinib 150mg orally once daily.
Biological: HS110 vaccine
0.5ml to be administered twice weekly for 18 weeks (36 doses)
Biological: HS110 vaccine
0.5 mls to be dosed twice weekly for 18 weeks (36 doses)
Placebo Comparator: Placebo vaccine + erlotinib 150mg orally once daily
Placebo vaccine buffered saline solution + erlotinib 150mg orally once daily
Biological: Placebo
0.5ml buffered saline placebo to be administered twice weekly for 18 weeks (36 doses)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Immunologic Response (defined as production of IFNƴ from CD8+ T cells as evaluated by ELISPOT assay)
Time Frame: Week 18
Immune response will be evalulated by ELISPOT assays and change will be assessed from baseline.
Week 18

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety of the combination of HS110 vaccine and erlotinib
Time Frame: Up to 1 year
Incidence and severity of adverse events, changes in laboratory measures, physical exams and evaluation of autoimmune phenomena.
Up to 1 year
Tumor assessment by immunologic response criteria (irRC)
Time Frame: Baseline, Week 12 and Week 22
Patients will have a CT scan performed at baseline, Week 12 and Week 22 or at the end of study visit in the case of early termination from study. Investigators will assess the disease response using irRC for overall response, CR, PR, SD or PD.
Baseline, Week 12 and Week 22
Exploratory Immunologic endpoint - evaluation of circulating tumor cells
Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12 and Week 18
Analysis via a semiautomated, epithelial cell adhesion molecule-based immunomagnetic technique.
Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12 and Week 18
Exploratory immunologic endpoint - immune function
Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12 and Week 18
Analysis of cell surfance molecules by flow cytometry
Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12 and Week 18
Exploratory immunologic endpoint - proteomic profile
Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12 and Week 18
Examination of protein expression utilizing western blot, immunohistochemical staining, enzyme linked immunosorbent assay (ELISA) or mass spectrometry
Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12 and Week 18

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Heat Biologics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: John Nemunaitis, MD, Mary Crowley Cancer Research Centers

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2011

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2013

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 20, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 4, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 5, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 21, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 20, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HS110-10-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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