Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
Trial record 1 of 1 for:    NCT03007732
Previous Study | Return to List | Next Study

Pembrolizumab in Combination With Intratumoral SD-101 Therapy

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2017 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
Lawrence Fong, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT03007732
First received: August 5, 2016
Last updated: April 12, 2017
Last verified: April 2017
  Purpose
This is a non-comparative open-label multicenter Phase 2 clinical trial combining definitive prostatic radiotherapy (RT) and pembrolizumab with or without intratumoral SD-101 in patients with newly diagnosed hormone-naive oligometastatic prostate cancer.

Condition Intervention Phase
Prostatic Neoplasms
Drug: Pembrolizumab
Drug: SD-101
Radiation: High Dose Rate (HDR) Brachytherapy
Other: Combined Androgen Blockage (CAB)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase 2 Trial Pembrolizumab or Pembrolizumab in Combination With Intratumoral SD-101 Therapy in Patients With Hormone-Naïve Oligometastatic Prostate Cancer Receiving Definitive Prostatic Radiation and Intermittent Androgen Deprivation Therapy

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Change Rate of PSA < nadir + 2 ng/mL [ Time Frame: Change from the start of treatment, 15 months, and 24 months ]
    To determine the rate of PSA < nadir + 2 ng/mL at 15 and 24 months in patients with non-castrate levels of testosterone in each study arm.


Secondary Outcome Measures:
  • Rate of testosterone-PSA uncoupling [ Time Frame: 24 months ]
    To determine the rate of testosterone-PSA uncoupling (section 4.2.3.1) in each study arm.

  • Time to clinical progression [ Time Frame: 24 months ]
    To estimate time to clinical progression in each study arm.

  • Number of participants with treatment-related adverse events as assessed by CTCAE (Common Terminology Criteria for Adverse Events) 4.0 [ Time Frame: 24 months ]
    Assess the safety associated with giving RT (radiation therapy) and pembrolizumab with or without intratumoral SD-101, based on number of participants with treatment-related adverse events as assessed by CTCAE (Common Terminology Criteria for Adverse Events) 4.0

  • Progression-free survival (PFS) [ Time Frame: 24 months ]
    To estimate progression-free survival (PFS) in each study arm.


Other Outcome Measures:
  • Assess peripheral and tumor-based biomarkers of response and resistance by immunohistochemistry of immune cell infiltrates, PD-L1 staining, and exploration of gene signature. [ Time Frame: 24 months ]
    Assess peripheral and tumor-based biomarkers of response and resistance by: 1) Immunohistochemistry of immune cell infiltrates on baseline biopsy tissues and optional progression biopsy tissues; 2) Assessment of PD-L1 staining on tumor and tumor-infiltrating immune cells (IC) on baseline biopsy tissues and optional progression biopsy tissues; 3) Exploration of gene signature in pre-treatment tumor biopsies that correlates with treatment response

  • Treatment-induced effects on circulating immune cells by flow cytometry [ Time Frame: 24 months ]
    To define the treatment-induced effects on circulating immune cells by flow cytometry

  • Explore remodeling of circulatory T cell repertoire in the tumor and blood by deep sequencing of VDJ (variable, diversity, joining) regions of TCRs (T-cell receptors). [ Time Frame: 24 months ]
    Explore the remodeling of circulating T cell repertoire by deep sequencing of VDJ regions of TCRs


Estimated Enrollment: 60
Anticipated Study Start Date: April 2017
Estimated Study Completion Date: March 2021
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Combined Androgen Blockade (CAB) x9 months then off High Dose Rate (HDR) Brachytherapy Pembrolizumab x 13 cycles
Drug: Pembrolizumab
Other Names:
  • MK-3475
  • Keytruda
Radiation: High Dose Rate (HDR) Brachytherapy Other: Combined Androgen Blockage (CAB)
Other Name: intermittent androgen deprivation therapy
Experimental: Arm 2
Combined Androgen Blockade (CAB) x9 months then off High Dose Rate (HDR) Brachytherapy Pembrolizumab x 13 cycles Intratumoral SD-101 (D1 and D3 of High Dose Rate (HDR) brachytherapy)
Drug: Pembrolizumab
Other Names:
  • MK-3475
  • Keytruda
Drug: SD-101
Other Name: Toll-like receptor 9
Radiation: High Dose Rate (HDR) Brachytherapy Other: Combined Androgen Blockage (CAB)
Other Name: intermittent androgen deprivation therapy

Detailed Description:
A safety lead-in for each treatment arm will be performed prior to full 1:1 randomization into each arm. Definitive RT to the whole prostate gland will be delivered via high-dose rate (HDR) brachytherapy on Day 1 and Day 8 (+7 days) of Cycle 1 pembrolizumab in each arm. Immediately before RT, SD-101 will be delivered to the dominant prostatic lesion on Day 1 and Day 8 (+7 days) of Cycle 1 pembrolizumab in Arm 2. SD-101 will be administered intratumorally in concert with placement of the HDR brachytherapy catheters. Pembrolizumab will be continued for a total of 13 cycles, until disease progression, or unacceptable toxicity, whichever occurs first. Patients will receive 3 months of androgen deprivation therapy (ADT) run-in, followed by combined androgen blockade (CAB) for 9 months, then discontinuation of ADT. Primary outcome is to evaluate the rate of prostate specific antigen (PSA) < nadir +2 ng/mL at 15 and 24 month from the start of treatment among patients with non-castrate levels of testosterone (>150 ng/dL). Serum, archival prostate biopsy, mandatory baseline metastatic tumor biopsy, and optional repeat biopsy at time of progression, will be obtained to characterize circulating and intratumoral immune responses.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be willing and able to provide written informed consent/assent for the trial.
  • Be >=18 years of age on day of signing informed consent.
  • Have a performance status of 0 or 1 on the ECOG Performance Scale.
  • Histologically documented adenocarcinoma of the prostate
  • Oligometastatic disease. In order to be eligible, the patient must have a total of <4 metastatic bone and/or metastatic lymph node sites based on bone and/or soft tissue lesions as defined by any of the following:

    1. Bone metastases will be defined by bone imaging. If the patient has technetium bone scan, and/or NaF PET performed, either study may be used for documenting metastases; both scans do not need to show the number of metastases required for study entry. For patients undergoing PSMA PET, only PSMA avid lesions that have a CT or MRI correlate consistent with metastasis will be counted as a site of metastasis.
    2. Distant metastatic lymph node disease. A lymph node ≥1 cm in shortest dimension will be noted as involved with disease. Distant metastatic lymph nodes will be determined as any lymph nodes outside the confines of the true pelvis. For patients undergoing PSMA PET, only PSMA avid lesions that have a CT or MRI correlate consistent with metastasis will be counted as a site of metastasis.
    3. Any other soft tissue lesion deemed by the physician to be consistent with distant metastatic disease i.e. lung and liver metastases. For patients undergoing PSMA PET, only PSMA avid lesions that have a CT or MRI correlate consistent with metastasis will be counted as a site of metastasis.
  • Treatment naïve, defined as less than 2 months of standard of care ADT (e.g. GNRH agonist or antagonist with or without antiandrogen) for metastatic hormone-sensitive prostate cancer prior to enrollment
  • No prior chemotherapy for prostate cancer
  • Not a candidate for or refuse chemotherapy
  • No prior prostatectomy or prostatic radiation
  • PSA >2 ng/mL at baseline or prior to initiation of hormonal therapy
  • Baseline testosterone >150 ng/dL if patient has not initiated hormonal therapy
  • Available archival tumor tissue for correlative studies. Submission of archival TRUS prostate biopsy tissue is required if available, in the form of representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (preferred) or at least 15 slides, with an associated pathology report. If archival prostate tissue are unavailable or cannot be obtained, a repeat TRUS prostate biopsy is not required for eligibility.
  • Consent to undergo a mandatory baseline biopsy of a metastatic tumor, if clinically feasible and safe to perform. Acceptable samples include core needle biopsies of bone or lymph node. At least three cores should be obtained. A fine needle aspirate is not acceptable. Subjects have the option of consenting to a repeat biopsy at time of progression.
  • Consent to undergo mandatory intra-operative prostatic core biopsies at the time of HDR brachytherapy with or without SD-101 therapy, depending on study arm.
  • The effects of pembrolizumab on the developing human fetus is unknown. Men treated or enrolled on this protocol must agree to use adequate contraception prior to the first dose of study therapy, for the duration of the study participation, and for 120 days after the last dose of study therapy.
  • Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.

Adequate Organ Function Laboratory Values:

  • Absolute neutrophil count (ANC) ≥1,500 /mcL
  • Platelets ≥100,000 / mcL
  • Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
  • Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
  • Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
  • Albumin >2.5 mg/dL
  • International Normalized Ratio (INR) or Prothrombin Time (PT)
  • Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Creatinine clearance should be calculated per institutional standard.
  • Subjects should agree to use an adequate method of contraception prior to the first dose of study therapy through 120 days after the last dose of study therapy.
  • Their partners should also be encouraged to use proper method of contraception.

Exclusion Criteria:

  • Patients who are not appropriate candidates for prostate brachytherapy.
  • Patients with neuroendocrine or small cell features are not eligible.
  • Patients with evidence of liver metastasis are excluded.
  • GNRH agonists or GNRH antagonists (e.g., leuprorelin, degarelix) for > 2 months prior to enrollment
  • Antiandrogens (e.g., bicalutamide, flutamide, nilutamide) for > 2 months prior to enrollment. Patients on 5-alpha reductase inhibitors are allowed on study.
  • Estrogen containing compounds for > 2 months prior to enrollment
  • Novel androgen-directed therapies approved for CRPC (e.g., abiraterone, enzalutamide) for any duration
  • PC-SPES or PC-x products. Other herbal therapies or supplements will be considered by the Principle Investigator on a case-by-case basis based on their potential for hormonal or anti-cancer therapies.
  • Prior immunotherapy or chemotherapy for prostate cancer
  • Prior radiation therapy to the prostate
  • Prior prostatectomy
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment, with the exception of steroids for adrenal insufficiency in which case prednisone <10mg/day or its equivalent is allowed.
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has known history of, or any evidence of active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Expecting to father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy.
  • Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed within 30 days.
  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: NCT03007732

Contacts
Contact: Julie McCluggage, RN 415-514-8133 Julie.McCluggage@ucsf.edu
Contact: Joanne Otani, NP 415-502-2756 Joanne.Otani@ucsf.edu

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
University of California San Francisco Not yet recruiting
San Francisco, California, United States, 94115
Contact: Julie McCluggage, RN    415-514-8133    Julie.McCluggage@ucsf.edu   
Contact: Lissa Gray, NP    415-514-8133    Lissa.Gray@ucsf.edu   
Principal Investigator: Lawrence Fong, MD         
Sponsors and Collaborators
Lawrence Fong
Investigators
Principal Investigator: Lawrence Fong, MD University of California, San Francisco
  More Information

Responsible Party: Lawrence Fong, Proffesor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03007732     History of Changes
Other Study ID Numbers: 16703
Study First Received: August 5, 2016
Last Updated: April 12, 2017
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Androgens
Ascorbic Acid
Estrogens, Conjugated (USP)
Methyltestosterone
Pembrolizumab
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Vitamins
Micronutrients
Growth Substances
Estrogens
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents

ClinicalTrials.gov processed this record on April 21, 2017