Working… Menu

Dose Escalation Study of ADXS31-164 in Subjects With HER2 Expressing Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02386501
Recruitment Status : Completed
First Posted : March 12, 2015
Last Update Posted : July 16, 2020
Information provided by (Responsible Party):
Advaxis, Inc.

Brief Summary:
This is a Phase 1b, multicenter, open-label, dose-escalation study designed to estimate the maximum tolerated dose (MTD) and determine the recommended Phase 2 dose (RP2D) of ADXS31-164. Once the RP2D has been selected, up to 4 expansion cohorts will be evaluated.

Condition or disease Intervention/treatment Phase
HER2 Expressing Solid Tumors Drug: ADXS31-164 Phase 1 Phase 2

Detailed Description:

This is a Phase 1b, dose-escalation, open-label study in subjects with HER2 expressing solid tumors. Subjects will receive escalating doses of ADXS31-164 every 3 weeks during a 12-week treatment cycle. Subjects will receive a prophylactic regimen completed at least 30 minutes prior to each ADXS31-164 infusion to mitigate and manage the potential immune response seen with immunotherapy administration. In addition, all subjects will participate in a 3 year Lm surveillance period. The surveillance period will begin following the last dose of study treatment or at the time of study discontinuation. This period is intended to help ensure the eradication of Lm bacteria. This period will also include a 6- month course of trimethoprim/sulfamethoxazole which will be initiated approximately 72 hours after the completion of the last dose of ADXS31-164 or immediately following study discontinuation. In subjects with a sulfa allergy, the 6-month course should consist of ampicillin 500 mg 4 times daily initiated approximately 72 hours following the last dose of study treatment or immediately following study discontinuation.

Dose escalations and de-escalations will be dictated by a 3+3 design. Three dose levels may be evaluated during the dose escalation portion starting with Dose Level 1 at 1 x 109 colony forming units (CFU). Once the Maximum Tolerated Dose (MTD) and RP2D have been identified, up to 4 HER2 overexpressing tumor specific expansion cohorts will be evaluated. The specific tumor types included in the expansion cohorts may include breast and gastric cancer with the remaining to be determined by the sponsor after review of data from Part A. Treatment cycles can be repeated at the RP2D (or less) for each subject for up to 2 years, until a study discontinuation criterion is met or he/she has completed >6 months of study therapy and at least 1 cycle of treatment post observation of a complete response (CR)

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Dose Escalation Study of ADXS31-164 in Subjects With HER2 Expressing Solid Tumors
Actual Study Start Date : September 2015
Actual Primary Completion Date : April 2017
Actual Study Completion Date : September 2018

Arm Intervention/treatment
Experimental: ADXS31-164
Dose/Potency 5 x 108 CFU; 1 x 109 CFU; 5 x 109 CFU; 1 x 1010 CFU
Drug: ADXS31-164

Primary Outcome Measures :
  1. Number of patients with dose-limiting toxicities for each dose level as assessed by CTCAE v 4.0 [ Time Frame: 4 Months ]
  2. Frequency and severity of adverse effects as assessed by CTCAE v 4.0 [ Time Frame: 3 Years ]
    The type, incidence, severity, and causality of each AE, the duration of the event, and any required treatment interventions will be tabulated.

Secondary Outcome Measures :
  1. Proportion of patients who have objective tumor response (complete or partial) [ Time Frame: 3 Years ]
    Tumor response will be evaluated by RECIST 1.1 and irRECIST criteria.

  2. Changes in clinical immunology based upon serum [ Time Frame: Baseline through 12 Weeks ]
    Immunologic effects will be measured and evaluated by collection of peripheral blood for preparation of peripheral blood mononuclear cells (PBMCs) and serum at baseline, prior to each treatment and posttreatment in the first treatment cycle only.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • HER2 Positive
  • Have histological or cytological diagnosis of locally advanced/metastatic HER2 solid tumors that has progressed or become intolerant to standard therapy or for which no standard therapy is available
  • Have measurable and/or evaluable disease based on RECIST 1.1.
  • ECOG performance status of 0 to 1

Exclusion Criteria:

  • Is newly diagnosed with a curative treatment option available.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of' immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has had a prior monoclonal antibody therapy within 2 weeks prior to study Day 1. (Prior anti-HER2 therapy is acceptable).
  • Has received anticancer chemotherapy, surgical treatment, and/or radiation therapy (except palliative radiation therapy for disease-related pain with a consult with the sponsor's medical monitor) within ≤2 weeks of first study treatment.
  • Is dependent on, currently or has received within the past 4 weeks corticosteroids (hormone replacement therapy, topical corticosteroids and occasional inhaled corticosteroids are allowed).
  • Has a contraindication to administration of trimethoprim/sulfamethoxazole or ampicillin.
  • Has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)). NOTE: More common devices and prosthetics which include arterial and venous stents, dental and breast implants, and venous access devices (e.g., Port-a-Cath or Mediport) are permitted. Sponsor must be contacted prior to consenting any subject who has any other device and/or implant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02386501

Layout table for location information
United States, California
Not Yet Recruiting
Los Angeles, California, United States
United States, Colorado
Aurora, Colorado, United States
United States, Michigan
Grand Rapids, Michigan, United States
United States, North Carolina
Charlotte, North Carolina, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Texas
Dallas, Texas, United States
Sponsors and Collaborators
Advaxis, Inc.
Layout table for additonal information
Responsible Party: Advaxis, Inc. Identifier: NCT02386501    
Other Study ID Numbers: 164-05
First Posted: March 12, 2015    Key Record Dates
Last Update Posted: July 16, 2020
Last Verified: July 2020
Additional relevant MeSH terms:
Layout table for MeSH terms