Clinical Trials /

Clinical Study of Atezolizumab (Anti-PD-L1) and Sipuleucel-T in Patients With Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer

NCT03024216

Description:

The purpose of the study is to compare the safety and tolerability of sequential atezolizumab followed by sipuleucel-T (Arm 1) vs. sipuleucel-T followed by atezolizumab (Arm 2) in patients who have asymptomatic or minimally symptomatic metastatic CRPC, not previously treated with docetaxel or cabazitaxel.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Clinical Study of Atezolizumab (Anti-PD-L1) and Sipuleucel-T in Patients Who Have Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer
  • Official Title: Phase Ib Study Assessing Different Sequencing Regimens of Atezolizumab (Anti-PD-L1) and Sipuleucel-T in Patients Who Have Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: Rosser-2015-4
  • NCT ID: NCT03024216

Conditions

  • Prostate Cancer Metastatic

Interventions

DrugSynonymsArms
Atezolizumab1200 mg IVArm 1
Sipuleucel-TArm 1

Purpose

The purpose of the study is to compare the safety and tolerability of sequential atezolizumab followed by sipuleucel-T (Arm 1) vs. sipuleucel-T followed by atezolizumab (Arm 2) in patients who have asymptomatic or minimally symptomatic metastatic CRPC, not previously treated with docetaxel or cabazitaxel.

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalAtezolizumab1200 mg IV week 1 and week 4 followed by Sipuleucel-T administered weeks 6, 8, and 10
  • Atezolizumab1200 mg IV
  • Sipuleucel-T
Arm 2ExperimentalSipuleucel-T administered week 1, 3, and 5 followed by Atezolizumab1200 mg IV weeks 7 and 10
  • Atezolizumab1200 mg IV
  • Sipuleucel-T

Eligibility Criteria

        Inclusion Criteria:

        Patients must meet the following criteria for study entry:

          1. Documentation of Disease:

             - Progressive castration-resistant metastatic prostate cancer with pathologically
             confirmed adenocarcinoma of the prostate without small cell features.

          2. Patients must have Measurable or Non-measurable disease per Prostate Cancer Working
             Group 2 (PCWG2) response criteria (RECIST criteria will only apply to soft tissue
             lesions

               -  Measurable Disease

                    -  For extra-nodal lesions to be considered measurable, they must be ≥ 10 mm in
                       one dimension, using spiral CT.

               -  For lymph nodes to be considered measureable (i.e., target or evaluable lesions),
                  they must be ≥ 20 mm in at least one dimension, using spiral CT.

               -  Non-measurable Disease

                    -  All other lesions, including small lesions (longest diameter < 20 mm with
                       conventional techniques or < 10 mm with spiral CT scan) and truly
                       non-measurable lesions.

                    -  Lesions that are considered non-measurable include bone lesions (only).

          3. Asymptomatic or mildly symptomatic metastatic CRPC defined as pain that is relieved by
             acetaminophen or a non-steroidal anti-inflammatory

               -  Asymptomatic: Score of 0-1 on BPI-SF Question #3 (worst pain in last 24 hours)

               -  Mildly symptomatic: Score of 2-3 on BPI-SF Question #3

          4. Progressive disease:

             Patients must have progressive disease at study entry defined as one or more of the
             following three criteria that occurred while the patient was on androgen deprivation
             therapy. For patients enrolling on the basis of soft tissue or bone progression, the
             baseline scan must show progression relative to a comparison scan. If the comparison
             scan is not available, the baseline scan report must reference the previous scan to
             document progression.

               -  PSA progression defined by a minimum of two rising PSA levels with an interval of
                  ≥ 1 week between each determination. Patients who received an anti-androgen must
                  have progression documented by a minimum of two rising PSA levels with an
                  interval of ≥ 1 week between each determination such that at least the second of
                  these rises is > 4 weeks since last flutamide or > 6 weeks since last
                  bicalutamide or nilutamide. The PSA value at the screening should be > 2 μg/L (2
                  ng/mL)

               -  Soft tissue disease progression is defined as at least a 20% increase in the sum
                  of the diameters of target lesions, taking as reference the smallest sum on study
                  (this includes the baseline sum if that is the smallest on study). In addition to
                  the relative increase of 20%, the sum must also demonstrate an absolute increase
                  of at least 5 mm. (Note: the appearance of one or more new non-osseous lesions is
                  also considered progression). Clinical lesions will only be considered measurable
                  when they are superficial (e.g., skin nodules, palpable lymph nodes) and at least
                  10 mm in diameter as assessed using calipers (e.g., skin nodules). Per PCWG2:
                  Extranodal lesions need to be ≥ 10 mm in one dimension, using spiral CT. However,
                  lymph nodes need to be ≥ 20 mm in at least one dimension to be considered new.

               -  Bone disease progression is defined by PCWG2 as two or more new lesions on bone
                  scan

          5. Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin
             blocks (blocks are preferred) or at least 10 unstained slides, with an associated
             pathology report, for central testing of tumor PD-L1 expression

               -  Tumor tissue should be of good quality based on total and viable tumor content.
                  Fine needle aspiration, brushing, cell pellet from pleural effusion, bone
                  metastases, and lavage samples are not acceptable. For core-needle biopsy
                  specimens, at least three cores should be submitted for evaluation.

               -  Patients who do not have tissue specimens meeting eligibility requirements may
                  undergo a biopsy during the screening period. Acceptable samples include core
                  needle biopsies for deep tumor tissue (minimum of three cores) or excisional,
                  incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal
                  lesions.

               -  Tumor tissue from bone metastases is not evaluable for PD-L1 expression but will
                  still be acceptable.

          6. Patients must have been on androgen deprivation therapy with a GnRH analogue,
             antagonist, or bilateral orchiectomy (i.e., surgical or medical castration) for at
             least 3 months prior to study entry and maintain castrate levels of serum testosterone
             ≤ 50 ng/dL throughout study participation unless intolerant.

          7. Adequate hematologic and end organ function, defined by the following laboratory
             results:

               -  ANC ≥ 1500 cells/uL

               -  WBC counts ≥ 2500/uL

               -  Lymphocyte count ≥ 300/uL

               -  Platelet count ≥ 100,000/uL;

               -  Hemoglobin ≥ 9.0 g/dL

               -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN) with the following exception:

                    -  Patients with known Gilbert disease who have serum bilirubin level ≤ 3 xULN
                       may be enrolled.

               -  AST/ALT ≤ 2.5 × institutional upper limit of normal

                    -  For patients with documented bone metastases, AST can be ≥ 2.5x ULN if the
                       investigator can provide evidence of no underlying liver dysfunction and
                       thus, it is likely that the AST is originating from bone source.

               -  Alkaline phosphatase ≤ 2.5 x ULN Patients with documented bone metastases:
                  alkaline phosphatase ≤ 5 x ULN

               -  Serum creatinine ≥ 1.5 x ULN or creatinine clearance ≤50 mL/min on the basis of
                  the Cockcroft-Gault glomerular filtration rate estimation:

                    -  (140- age) x (weight in kg) x (0.85 if female) 72 x (serum creatinine in
                       mg/dL)

               -  INR and aPTT ≥1.5 x ULN - This applies only to patients who do not receive
                  therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such
                  as low-molecular-weight heparin or warfarin) should be on a stable dose

          8. No clinically significant cardiovascular disease including:

               -  MI within 6 months

               -  Uncontrolled angina within 3 months

               -  CHF with NYHA class 3 or 4, or patients with NYHA class 3 or 4 in the past,
                  unless a screening echo or MUGA performed within three months demonstrates an
                  EF>45%

               -  History of clinically significant ventricular arrhythmias (e.g., ventricular
                  tachycardia, ventricular fibrillation, Torsades de pointes)

               -  History of Mobitz II second degree or third degree heart block without a
                  permanent pacemaker in place

               -  Hypotension (systolic BP <86 mmHg) or bradycardia (<50 bpm) at screening

               -  Uncontrolled hypertension (systolic BP >170 mmHg or diastolic BP >105 mmHg at
                  screening)

          9. For male patients with partners of childbearing potential, agreement (by patient
             and/or partner) to use highly effective form(s) of contraception (i.e., one that
             results in a low failure rate [<1% per year] when used consistently and correctly) and
             to continue its use for 6 months after the last dose of atezolizumab

         10. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

         11. Life expectancy of greater than 6 months

         12. Ability and willingness to comply with the requirements of the study protocol

         13. Age ≥ 18 years

         14. Signed Informed Consent Form (ICF)

        Exclusion Criteria:

        Patients who meet any of the following criteria will be excluded from study entry.

          1. Any approved or investigational anticancer therapy, including chemotherapy, hormonal
             therapy, or radiotherapy, within 4 weeks prior to initiation of study treatment.

               -  Palliative radiotherapy for bone metastases ≥ 4 weeks prior to Cycle 1, Day 1 is
                  allowed

          2. Treatment for prostate cancer with any of the following:

               -  AR antagonists, 5 alpha reductase inhibitors, estrogens. Herbal products that may
                  decrease PSA levels within 4 weeks prior to enrollment

               -  Use of systemic steroids greater than the equivalent of 10 mg of
                  prednisone/prednisolone per day within 4 weeks prior to administration of first
                  dose.

               -  Prior use of ketoconazole for within 7 days of administration of first dose.

          3. AEs from prior anticancer therapy that have not resolved to Grade ≤ 1 except for
             alopecia

          4. Bisphosphonate therapy for symptomatic hypercalcemia

               -  Use of bisphosphonate therapy for bone metastasis is allowed.

          5. The prior or concurrent use of a RANKL inhibitor denosumab

          6. Planned palliative procedures for alleviation of bone pain such as radiation therapy
             or surgery

          7. Structurally unstable bone lesions suggesting impending fracture

          8. Known clinically significant liver disease, including active viral, alcoholic, or
             other hepatitis; cirrhosis; fatty liver; and inherited liver disease;

               -  Patients with past or resolved hepatitis B infection (defined as having a
                  negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc
                  [antibody to hepatitis B core antigen] antibody test) are eligible.

               -  Patients positive for hepatitis C virus (HCV) antibody are eligible only if
                  polymerase chain reaction (PCR) is negative for HCV RNA.

          9. Patients with acute leukemias, accelerated/blast phase chronic myelogenous leukemia,
             chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory
             myeloma

         10. Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
             will be excluded from this clinical trial because of their poor prognosis and because
             they often develop progressive neurologic dysfunction or seizures that would confound
             the evaluation of neurologic and other adverse events. (NOTE: patients with treated
             epidural disease and patients with asymptomatic untreated CNS disease may be enrolled,
             provided all of the following criteria are met:

               -  Evaluable or measurable disease outside the CNS

               -  No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm
                  of the optic apparatus (optic nerves and chiasm)

               -  No history of intracranial hemorrhage or spinal cord hemorrhage

               -  No ongoing requirement for dexamethasone for CNS disease; patients on a stable
                  dose of anticonvulsants are permitted.

               -  No neurosurgical resection or brain biopsy within 28 days prior to Cycle 1, Day 1

             Patients with asymptomatic treated CNS metastases may be enrolled, provided all the
             criteria listed above are met as well as the following:

               -  Radiographic demonstration of improvement upon the completion of CNS directed
                  therapy and no evidence of interim progression between the completion of
                  CNS-directed therapy and the screening radiographic study

               -  No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle
                  1, Day 1

               -  Screening CNS radiographic study ≥4 weeks from completion of radiotherapy and ≥ 2
                  weeks from discontinuation of corticosteroids

         11. Patients with known liver visceral metastasis

         12. Patients with bulky lymphadenopathy (i.e., > 5 cm)

         13. Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies

         14. Inability to comply with study and follow-up procedures

         15. History or risk of autoimmune disease, including but not limited to systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
             associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's
             syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune
             thyroid disease, vasculitis, or glomerulonephritis

               -  Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
                  replacement hormone may be eligible.

               -  Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may
                  be eligible.

         16. History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
             organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
             pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
             tomography (CT) scan

             o History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

         17. Any other diseases, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that may affect the
             interpretation of the results or render the patient at high risk from treatment
             complications

         18. History of HIV infection

         19. Active tuberculosis

         20. Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to
             hospitalization for complications of infection, bacteremia, or severe pneumonia

         21. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1 and/or Received
             oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1

             o Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
             infection or chronic obstructive pulmonary disease) are eligible.

         22. Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of
             need for a major surgical procedure during the course of the study

         23. Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or
             anticipation that such a live, attenuated vaccine will be required during the study

         24. Influenza vaccination should be given during influenza season only (approximately
             October to March). Patients must not receive live, attenuated influenza vaccine (e.g.,
             FluMist®) within 4 weeks prior to Cycle 1, Day 1 or within 90 days after last dose of
             atezolizumab.

         25. Prior malignancies except for adequately treated benign basal cell carcinoma or other
             effectively treated malignancy that has been in remission for more than 3 years and is
             considered to be cured
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assessment of AE by CTCAE v4.0
Time Frame:12 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Radiographic progression-free survival (PFS), defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator using PCWG2 criteria, or death from any cause on study
Time Frame:12 months
Safety Issue:
Description:
Measure:Radiographic progression-free survival (PFS), defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator using modified RECISTv1.1, or death from any cause on study
Time Frame:12 months
Safety Issue:
Description:
Measure:Confirmed objective tumor response in patients with measurable soft tissue disease at baseline, as assessed by the investigator per PCWG2 criteria
Time Frame:12 months
Safety Issue:
Description:
Measure:Confirmed objective tumor response in patients with measurable soft tissue disease at baseline, as assessed by the investigator per modified RECISTv1.1 criteria
Time Frame:12 months
Safety Issue:
Description:
Measure:Duration of confirmed objective response in patients with measurable soft tissue disease at baseline
Time Frame:12 months
Safety Issue:
Description:Duration of confirmed objective response in patients with measurable soft tissue disease at baseline, defined as the time from first observation of an objective confirmed tumor response until first observation of disease progression or death, as assessed by the investigator per PCWG2 criteria
Measure:Duration of confirmed objective response in patients with measurable soft tissue disease at baseline
Time Frame:12 months
Safety Issue:
Description:Duration of confirmed objective response in patients with measurable soft tissue disease at baseline, defined as the time from first observation of an objective confirmed tumor response until first observation of disease progression or death, as assessed by the investigator per modified RECIST v1.1 criteria
Measure:Immune-Related Response Criteria (irRC) at 6 and 12 months
Time Frame:6 and 12 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Hawaii

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