Clinical trial NCT01482949: A Rollover Protocol for Subjects Previously Treated With AGS-003
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Renal Cell Carcinoma
Keywords: RCC
Kidney Cancer
Renal Cancer
Arcelis
Lead sponsor: Argos Therapeutics
Sponsor class: INDUSTRY
First posted: 2011-12-01
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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 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.

Primary outcomes:
measure: Tumor response
timeFrame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months.
Secondary outcomes:
measure: Clinical benefit (stable disease or response)
timeFrame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months.
measure: Immune function
timeFrame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months.
measure: Progression Free Survival (PFS)
timeFrame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months.
measure: Overall Survival (OS)
timeFrame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months.
measure: Treatment-emergent Adverse Events
timeFrame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months.
measure: Monitor clinical chemistry, hematology, and urinalysis for treatment-emergent changes from baseline
timeFrame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months.
measure: Physical Examinations
timeFrame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months.
measure: Vital Signs
timeFrame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months.
measure: Monitor signs and symptoms indicating treatment-emergent autoimmunity
timeFrame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months.
measure: Monitor for lymph node adenopathy
timeFrame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months.
measure: Injection Site Reaction
timeFrame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months.
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
Study officials:
affiliation: Argos Therapeutics
name: Lee F Allen, M.D., Ph.D.
role: STUDY_DIRECTOR
References: