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Trial record 1 of 1 for:    NCT03007732
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Pembrolizumab in Combination With Intratumoral SD-101 Therapy

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ClinicalTrials.gov Identifier: NCT03007732
Recruitment Status : Suspended (Modification to protocol mode of radiation therapy)
First Posted : January 2, 2017
Last Update Posted : January 30, 2018
Sponsor:
Information provided by (Responsible Party):
Lawrence Fong, University of California, San Francisco

Brief Summary:
This is a non-comparative open-label multicenter Phase 2 clinical trial combining stereotactic body radiation therapy (SBRT) and pembrolizumab with or without intratumoral SD-101 in patients with newly diagnosed hormone-naive oligometastatic prostate cancer.

Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Drug: Pembrolizumab Drug: SD-101 Drug: Leuprolide acetate Drug: Abiraterone Acetate Drug: Prednisone Radiation: Stereotactic Body Radiation Therapy Phase 2

Detailed Description:
This randomized phase II trial studies how well androgen deprivation therapy, pembrolizumab, and stereotactic body radiation therapy with or without TLR9 agonist SD-101 in treating patients with prostate cancer that has spread to other places in the body. Androgen can cause the growth of tumor cells. Androgen deprivation therapy, such as leuprolide acetate, prednisone, and abiraterone acetate may lessen the amount of androgen made by the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Colony-stimulating factors, such as TLR9 agonist SD-101, may increase the production of blood cells. It is not yet known whether giving androgen deprivation therapy, pembrolizumab, and stereotactic body radiation therapy with or without TLR9 agonist SD-101 may work better in treating patients with prostate cancer.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
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
Actual Study Start Date : April 27, 2017
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Arm 1

Patients receive ADT including leuprolide acetate IM at baseline and then every 3 months for 3 doses, prednisone PO daily for 12 months, and abiraterone acetate PO daily for 12 months in the absence of disease progression or unacceptable toxicity. Patients are then randomized into 1 of 2 arms.

Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also undergo (Stereotactic Body Radiation Therapy) SBRT QOD over 10-14 days. Treatment with pembrolizumab repeats every 21 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Drug: Pembrolizumab
200 mg IV every 21 days for up to 13 doses (Arms 1 and 2)
Other Names:
  • MK-3475
  • Keytruda

Drug: Leuprolide acetate
22.5 mg will be given IM. First injection 3 months prior to Cycle 1 Day 1. Intermittent androgen deprivation therapy will be given every 3 months starting Cycle 1, Day 1 for 3 additional doses.
Other Name: Intermittent androgen deprivation therapy

Drug: Abiraterone Acetate
1000 mg oral dosage will be given daily for 3 months prior to Cycle 1, Day 1 and daily for 9 months starting Cycle 1, Day 1.
Other Name: Intermittent androgen deprivation therapy

Drug: Prednisone
5 mg oral dosage will be given daily for 3 months prior to Cycle 1 Day 1 and daily for 9 months starting Cycle 1, Day 1.
Other Name: Intermittent androgen deprivation therapy

Radiation: Stereotactic Body Radiation Therapy
7 Gy x 5 fractions (35 Gy total) 1-2 weeks after fiducial marker placement and simulation over 10-14 days.
Other Name: SBRT

Experimental: Arm 2

Patients receive ADT including leuprolide acetate IM at baseline and then every 3 months for 3 doses, prednisone PO daily for 12 months, and abiraterone acetate PO daily for 12 months in the absence of disease progression or unacceptable toxicity. Patients are then randomized into 1 of 2 arms.

Patients receive TLR9 agonist SD-101 intratumorally 1-2 weeks before Cycle 1, Day 1 and 21 days later after the first dose. Patients also receive pembrolizumab IV over 30 minutes on day 1 and undergo (Stereotactic Body Radiation Therapy) SBRT QOD over 10-14 days. Treatment with pembrolizumab repeats every 21 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Drug: Pembrolizumab
200 mg IV every 21 days for up to 13 doses (Arms 1 and 2)
Other Names:
  • MK-3475
  • Keytruda

Drug: SD-101
5 mg will be delivered to the dominant prostatic tumor lesion at time of fiducial marker placement (1-2 weeks prior to Cycle 1, Day 1) and 21 days after the 1st injection of SD-101.
Other Name: Toll-like receptor 9

Drug: Leuprolide acetate
22.5 mg will be given IM. First injection 3 months prior to Cycle 1 Day 1. Intermittent androgen deprivation therapy will be given every 3 months starting Cycle 1, Day 1 for 3 additional doses.
Other Name: Intermittent androgen deprivation therapy

Drug: Abiraterone Acetate
1000 mg oral dosage will be given daily for 3 months prior to Cycle 1, Day 1 and daily for 9 months starting Cycle 1, Day 1.
Other Name: Intermittent androgen deprivation therapy

Drug: Prednisone
5 mg oral dosage will be given daily for 3 months prior to Cycle 1 Day 1 and daily for 9 months starting Cycle 1, Day 1.
Other Name: Intermittent androgen deprivation therapy

Radiation: Stereotactic Body Radiation Therapy
7 Gy x 5 fractions (35 Gy total) 1-2 weeks after fiducial marker placement and simulation over 10-14 days.
Other Name: SBRT




Primary Outcome Measures :
  1. 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 :
  1. 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.

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

  3. 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

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


Other Outcome Measures:
  1. 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

  2. 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

  3. 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

  4. To explore the concordance of PSMA-positron emission tomography (PET) scanning [ Time Frame: 24 months ]
    To explore the concordance of PSMA-positron emission tomography (PET) scanning with conventional imaging in oligometastatic prostate cancer patients.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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 are 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 are 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. 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, including abiraterone) for metastatic hormone-sensitive prostate cancer prior to enrollment (at the time of consent)
  • 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, for those patients who have already initiated hormonal therapy, baseline testosterone is not required
  • 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 prostatic core biopsies at the time of fiducial marker placement and 21 days (+/- 7 days) after 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.
  • 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.
  • 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 (Performed within 10 days of treatment initiation):

  • 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. Creatinine clearance should be calculated per institutional standard
  • 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.

Exclusion Criteria:

  • Patients who are not appropriate candidates for prostate SBRT.
  • 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 consenting
  • Antiandrogens (e.g., bicalutamide, flutamide, nilutamide, abiraterone, enzalutamide) for > 2 months prior to consenting. Patients on 5-alpha reductase inhibitors are allowed on study.
  • Estrogen containing compounds for > 2 months prior to consenting
  • 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 carcinoid, 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 steroid treatment for at least 14 days prior to the first dose of study 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03007732


Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
University of California San Francisco
San Francisco, California, United States, 94115
Sponsors and Collaborators
Lawrence Fong
Investigators
Principal Investigator: Lawrence Fong, MD University of California, San Francisco

Responsible Party: Lawrence Fong, Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03007732     History of Changes
Other Study ID Numbers: 16703
NCI-2017-01340 ( Registry Identifier: Clinical Trials Reporting Program )
First Posted: January 2, 2017    Key Record Dates
Last Update Posted: January 30, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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