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Prostate Cancer MetastaticPhase 1NCT03024216

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

A Phase 1 study testing Atezolizumab1200 mg IV and Sipuleucel-T in people with Prostate Cancer Metastatic, run by University of Hawaii at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer Metastatic
What is being tested?
Atezolizumab1200 mg IV and Sipuleucel-T
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
3 sitesUnited States
Study dates
6 Feb 2017to 31 Dec 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must meet the following criteria for study entry:
  • Documentation of Disease:
  • Progressive castration-resistant metastatic prostate cancer with pathologically confirmed adenocarcinoma of the prostate without small cell features.
  • 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.
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  • 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).
  • 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
  • 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
  • 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.
  • 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.
  • 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
  • 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)
  • 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
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Life expectancy of greater than 6 months
  • Ability and willingness to comply with the requirements of the study protocol
  • Age ≥ 18 years
  • Signed Informed Consent Form (ICF)

Who cannot join

  • Patients who meet any of the following criteria will be excluded from study entry.
  • 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
  • Treatment for prostate cancer with any of the following:
  • 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.
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  • Prior use of ketoconazole for within 7 days of administration of first dose.
  • AEs from prior anticancer therapy that have not resolved to Grade ≤ 1 except for alopecia
  • Bisphosphonate therapy for symptomatic hypercalcemia
  • Use of bisphosphonate therapy for bone metastasis is allowed.
  • The prior or concurrent use of a RANKL inhibitor denosumab
  • Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery
  • Structurally unstable bone lesions suggesting impending fracture
  • 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.
  • Patients with acute leukemias, accelerated/blast phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma
  • 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
  • Patients with known liver visceral metastasis
  • Patients with bulky lymphadenopathy (i.e., > 5 cm)
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Inability to comply with study and follow-up procedures
  • 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.
  • 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.
  • 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
  • History of HIV infection
  • Active tuberculosis
  • 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
  • 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.
  • 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
  • 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
  • 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.
  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • City of Hope National Medical Center

    Duarte, California, 91010

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • Prostate Oncology Specialists, Inc.

    Marina del Rey, California, 90292

Other trials in United States

About this study

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

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.

Being tested
Atezolizumab1200 mg IV, Sipuleucel-T

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Atezolizumab1200 mg IVDrug

    Subjects in ARM 1 will receive 2 doses of atezolizumab 1200 mg intravenously (week 1 and week 4). If no dose limiting toxicity continue onto maintenance, week 13 and receive atezolizumab 1200 mg intravenously every 3 weeks until toxicities or lack of clinical benefit. Subjects in ARM 2 will receive 2 doses at approximately 3 weeks each of atezolizumab 1200 mg intravenously (weeks 7 and 10). If no dose limiting toxicity, continue to receive atezolizumab 1200 mg intravenously every 3 weeks, starting week 13, until toxicities or lack of clinical benefit.

  • Sipuleucel-TDrug

    Subjects in ARM 1 will receive sipuleucel-T administered in 3 doses at approximately 2-week intervals (weeks 6, 8, 10). Subjects in ARM 2 will receive sipuleucel-T administered in 3 doses at approximately 2-week intervals (weeks 1, 3 and 5)

Study groups in NCT03024216
Study groupRoleWhat they receive
Arm 1ExperimentalAtezolizumab1200 mg IV week 1 and week 4 followed by Sipuleucel-T administered weeks 6, 8, and 10
Receives: Drug: Atezolizumab1200 mg IV; Drug: Sipuleucel-T
Arm 2ExperimentalSipuleucel-T administered week 1, 3, and 5 followed by Atezolizumab1200 mg IV weeks 7 and 10
Receives: Drug: Atezolizumab1200 mg IV; Drug: Sipuleucel-T

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Assessment of AE by CTCAE v4.0

    Measured: 12 months

  2. Clinically significant changes in vital signs and clinical laboratory results

    Measured: 12 months

Secondary outcomes (7)

  1. 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

    Measured: 12 months

  2. 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

    Measured: 12 months

  3. Confirmed objective tumor response in patients with measurable soft tissue disease at baseline, as assessed by the investigator per PCWG2 criteria

    Measured: 12 months

  4. Confirmed objective tumor response in patients with measurable soft tissue disease at baseline, as assessed by the investigator per modified RECISTv1.1 criteria

    Measured: 12 months

  5. Duration of confirmed objective response in patients with measurable soft tissue disease at baseline

    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

    Measured: 12 months

  6. Duration of confirmed objective response in patients with measurable soft tissue disease at baseline

    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

    Measured: 12 months

  7. Immune-Related Response Criteria (irRC) at 6 and 12 months

    Measured: 6 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2017 (estimated)
  2. Study start6 Feb 2017
  3. Primary completion31 Dec 2020
  4. Study completion31 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03024216
Sponsor's protocol ID
Rosser-2015-4
Status last verified
May 2021
First submitted
9 Jan 2017
Last updated
26 May 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Dorff T, Hirasawa Y, Acoba J, Pagano I, Tamura D, Pal S, Zhang M, Waitz R, Dhal A, Haynes W, Shon J, Scholz M, Furuya H, Chan OTM, Huang J, Rosser C. Phase Ib study of patients with metastatic castrate-resistant prostate cancer treated with different sequencing regimens of atezolizumab and sipuleucel-T. J Immunother Cancer. 2021 Aug;9(8):e002931. doi: 10.1136/jitc-2021-002931.

    PubMed 34376554

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab1200 mg IV and Sipuleucel-T in people with Prostate Cancer Metastatic, run by University of Hawaii at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 51 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assessment of AE by CTCAE v4.0 (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03024216, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2021.

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