A Rollover Protocol for Subjects Previously Treated With AGS-003

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Argos Therapeutics
ClinicalTrials.gov Identifier:
NCT01482949
First received: November 17, 2011
Last updated: January 22, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to evaluate clinical response to AGS-003 alone or in combination with sunitinib therapy.


Condition Intervention Phase
Renal Cell Carcinoma
Drug: AGS-003
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Rollover Phase II Study Testing the Biologic Activity and Safety of AGS-003 in Renal Cell Carcinoma Subjects With Prolonged Response or Stable Disease and Ongoing AGS-003 Treatment in Protocol AGS-003-004 or AGS-003-006

Resource links provided by NLM:


Further study details as provided by Argos Therapeutics:

Primary Outcome Measures:
  • Tumor response [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: No ]
    Clinical antitumor activity of AGS-003 will be assessed as an objective tumor response by Response Evaluation Criteria in Solid Tumors (RECIST).


Secondary Outcome Measures:
  • Clinical benefit (stable disease or response) [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: No ]
    Clinical benefit measured as Stable Disease (SD), Partial Response (PR), and Complete Response (CR) rate to the treatment regimen. Tumor response is verified using standard definitions of RECIST

  • Immune function [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
    Analyses of immune function will be performed. This will include, but not limited to, assessment of T cell and antigen presenting cell populations, including effector memory, cytotoxic lymphocytes (CTLs), and regulatory T cells. Blood and plasma specimens for these analyses will be collected at specified time points and is optional for subjects continuing with booster treatments.

  • Progression Free Survival (PFS) [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: No ]
    Evaluate PFS from the date of registration until PFS is reached per RECIST

  • Overall Survival (OS) [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: No ]
    Evaluate OS from date of registration unitl date of death.

  • Treatment-emergent Adverse Events [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
    Monitor incidence of treatment-emergent Adverse Events.

  • Monitor clinical chemistry, hematology, and urinalysis for treatment-emergent changes from baseline [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
    Clinical laboratory values will be monitored for changes from baseline.

  • Physical Examinations [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
    Monitor changes from baseline in physical examinations

  • Vital Signs [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
    Monitor changes from baseline in vital signs

  • Monitor signs and symptoms indicating treatment-emergent autoimmunity [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
    Autoimmunity evaluations will be measured by clinical signs and symptoms (e.g., rash, cytopenias, and arthralgias) and by laboratory assessments. These assessments will be monitored as long as the subject is receiving AGS-003.

  • Monitor for lymph node adenopathy [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
    The draining lymph nodes (axillary and inguinal) will be evaluated for changes from baseline in size, tenderness, or inflammation. These assessments will be monitored as long as the subject is receiving AGS-003.

  • Injection Site Reaction [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
    Monitor changes from baseline in injection site reactions.


Estimated Enrollment: 7
Study Start Date: September 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AGS-003 Monotherapy
Subjects will undergo Booster (AGS-003 at 3 month intervals). Subjects that will receive AGS-003 as a monotherapy will be on this arm.
Drug: AGS-003
Autologous Dendritic Cell Immunotherapy
Other Name: Arcelis
Experimental: AGS-003 in combination with sunitinib
Subjects will undergo Induction (AGS-003 every 3 weeks until 5 doses are administered) followed by Booster (AGS-003 at 3 month intervals). Subjects that will begin sunitinib therapy will be on this arm.
Drug: AGS-003
Autologous Dendritic Cell Immunotherapy
Other Name: Arcelis

Detailed Description:

AGS-003-005 is a rollover, open label, Phase II clinical study testing the biologic activity and safety of AGS-003 in subjects who have experienced either partial responses or prolonged stable disease and continue to benefit from ongoing treatment with AGS-003 in protocols AGS-003-004 or AGS-003-006.

Rollover subjects from AGS-003-004 will continue with AGS-003 monotherapy booster dosing until disease progression or until a discontinuation criterion is reached.

Subjects that progress on AGS-003 monotherapy (from the AGS-003-004 protocol) may start sunitinib treatment and re-initiate AGS-003 therapy beginning with the induction phase dosing schedule.

Rollover subjects from AGS-003-006 will continue sunitinib dosing in combination with booster dosing of AGS-003 until disease progression or until a discontinuation criterion is reached.

If a subject has disease progression due to a new tumor lesion, upon consultation between the investigator, Argos representatives and the Argos medical monitor, the subject may be considered for re-manufacture of study product (from the new metastatic lesion) and dosing with this new product in combination with sunitinib beginning with the induction phase dosing schedule.

For those subjects initiating treatment with the induction phase as described above, restaging imaging occurs at screening (baseline), prior to the fifth dose in the induction phase (as applicable) and every 12 weeks during the booster phase (at the start of the sunitinib holiday, 2 weeks prior to the next AGS-003 dose).

For subjects on combination therapy, if dosing with sunitinib is stopped due to sunitinib-related issues, treatment with AGS-003 may continue.

Close-out visits will occur upon disease progression (other than circumstances discussed above which are eligible for re-induction) or upon decision to terminate the study by the sponsor.

Quarterly follow-up for survival for each subject will occur by telephone interview for 1 year following the last AGS-003 administration or study termination.

  Eligibility

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

Inclusion Criteria:

  • Age ≥ 18 years
  • Subjects are receiving ongoing treatment with AGS-003 in protocol AGS- 003-004 or AGS-003-006.
  • Measurable disease that can be monitored per RECIST throughout the course of study participation.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate hematologic function, as defined by the following criteria:

    1. White blood cell (WBC) ≥ 4000/µL (≥ 4.0 x 103/µL)
    2. Absolute neutrophil count (ANC) ≥ 1500/µL (≥ 1.5 x 103/µL)
    3. Platelets ≥ 100,000/µL (≥ 100 x 103/µL)
    4. Hemoglobin (Hgb) ≥ 9.0 g/dL
  • Adequate renal and hepatic function, as defined by the following criteria:

    1. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or, if serum creatinine > 1.5 x ULN, estimated glomerular filtration rate (eGFR) ≥ 30 mL/min
    2. Total serum bilirubin ≤ 1.5 x ULN
    3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN, or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy
  • Adequate coagulation function as defined by the following criteria:

    1. Prothrombin time (PT) ≤ 1.5 x ULN
    2. Activated partial thromboplastin time (PTT) < 1.5 x ULN
    3. Corrected calcium ≤ 11.5 mg/dL
  • Negative serum pregnancy test for female subjects with reproductive potential, and agreement of all male and female subjects of reproductive potential to use a reliable form of contraception during the study and for 12 weeks after the last dose of study drug
  • Able to abstain from taking prohibited drugs, either prescription or non- prescription, during the treatment phase of the study
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
  • Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment
  • No brain metastases detected by magnetic resonance imaging (MRI).

Exclusion Criteria:

  • Any serious medical condition considered by the investigator to constitute an unwarranted high risk for investigational treatment
  • History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of brain or leptomeningeal disease on screening computed tomography (CT) scan or MRI
  • Pregnancy or breastfeeding
  • Active autoimmune disease or condition requiring chronic immunosuppressive therapy

NOTE: Abnormal laboratory values for autoimmunity markers in the absence of other signs/symptoms of autoimmune disease are not exclusionary.

  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: NCT01482949

Locations
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Indiana
The Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
United States, North Carolina
Blumenthal Cancer Center/Carolinas Medical Center
Charlotte, North Carolina, United States, 28204
United States, Virginia
Urology of Virginia - Sentara Medical Group
Norfolk, Virginia, United States, 23502
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Sponsors and Collaborators
Argos Therapeutics
  More Information

No publications provided

Responsible Party: Argos Therapeutics
ClinicalTrials.gov Identifier: NCT01482949     History of Changes
Other Study ID Numbers: AGS-003-005
Study First Received: November 17, 2011
Last Updated: January 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Argos Therapeutics:
RCC
Kidney Cancer
Renal Cancer
Arcelis

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on July 24, 2014