Clinical trial NCT04616547: Treatment of Cancer-Related Bone Pain by Using Bone-Targeted Radiation-Based Therapy (Sn-117m-DTPA) in Patients With Prostate Cancer That Has Spread to Bones
Official title: A Single Arm Phase II Study of Bone-Targeted Sn-117m-DTPA in Symptomatic Castration Resistant Prostate Cancer With Skeletal Metastases
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Castration-Resistant Prostate Carcinoma
Metastatic Malignant Neoplasm in the Bone
Metastatic Prostate Adenocarcinoma
Stage IV Prostate Cancer AJCC v8
Stage IVA Prostate Cancer AJCC v8
Stage IVB Prostate Cancer AJCC v8
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2020-11-05
Enrollment: 1
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial studies the effect of Sn-117m-DTPA on bone pain in patients with prostate cancer that has spread to the bones. Sn-117m-DTPA is a radioactive therapeutic agent that localizes to bones when given to patients. Sn-117m-DTPA may help reduce bone pain in patients with prostate cancer that has spread to the bones.

Detailed description: PRIMARY OBJECTIVE:

I. To evaluate the efficacy of tin-117m diethylenetriaminepentaacetic acid (Sn-117m-DTPA) on sustained pain response in patients with castration-resistant prostate cancer (CRPC) metastatic to at least two bone sites with at least one clinically meaningful pain at baseline (\>= 4 on an 11-point pain intensity scale).

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of Sn-117m-DTPA per Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.

II. To measure Sn-117m-DTPA activity by gamma-camera dosimetry scans (serial full body planar images) obtained at 1 hour, 4 hours (or within 4-6 hours), 24 hours (or within 16-24 hours), 48 hours (or within 36-48 hours), 72 hours (or within 60-72 hours), 1 week (+/- 2 days), and 4 weeks (+/- 2 days) after the first Sn-117m-DTPA administration.

III. To evaluate the therapeutic efficacy of Sn-117m-DTPA at 24 weeks as measured by Prostate Cancer Working Group 3 (PCWG3) criteria.

IV. To evaluate time to the first symptomatic skeletal event defined as i) the first use of external-beam radiation therapy to relieve skeletal symptoms; ii) new symptomatic pathologic vertebral or nonvertebral bone fractures; iii) spinal cord compression; or iv) tumor-related orthopedic surgical intervention.

V. To evaluate the overall pain response rate at 24 weeks. VI. To evaluate the duration of pain response defined as from the time of improvement in pain response (pain index =\< 3) until the pain recurs.

VII. To measure changes and time to progression in serum prostate-specific antigen (PSA) and serum alkaline phosphatase (ALP) levels.

VIII. To measure patient-reported outcomes (PROs) and adverse events (AEs) (PRO-CTCAE) captured by digital instruments.

IX. To evaluate progression-free survival (PFS) and overall survival (OS).

EXPLORATORY OBJECTIVES:

I. To examine any tumor genomic alterations that may be associated with response or resistance to Sn-117m-DTPA, a radiopharmaceutical agent.

II. To examine the changes in systemic inflammatory markers (such as interferon \[IFN\]-gamma, tumor necrosis factor \[TNF\]-alpha, interleukins \[IL\]-8, IL-10, and IL-17) by flow cytometry, and changes in markers of immune function by measuring the percentage and absolute number of CD4+ T helper cells, CD8+ T cytotoxic cells, T regulatory cells, polymorphonuclear (PMN) myeloid-derived suppressor cells (MDSCs), and mononuclear MDSCs (M-MDSCs) prior to treatment versus (vs.) end of cycle 1, end of cycle 2, and at week 24 and correlate values and/or changes with treatment outcomes.

III. To evaluate the feasibility of measuring polo-like kinase 1 (Plk1) expression via immunohistochemistry (IHC) staining on archival tissues.

OUTLINE:

Patients receive tin Sn 117m DTPA intravenously (IV) over 5-10 minutes on day 1. Treatment repeats every 8 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive tin Sn 117m DTPA for an additional 2 cycles if pain recurs within 6 months after a 16-week pain observation period and no disease progression on bone scans, or evidence of clinical progression.

After completion of study, patients are followed up every 4 weeks until week 28, and then every 3 months for up to 12 months after the first dose of tin Sn 117m DTPA.

Eligibility criteria: Inclusion Criteria:

* Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate that is castration-resistant, defined as:

  * A castrate serum testosterone level =\< 50 ng/dL or 1.7 nmol/L
  * Bilateral orchiectomy or maintenance on androgen ablation therapy with luteinizing hormone-releasing hormone (LHRH). Androgen deprivation therapy needs to be maintained throughout the study unless a patient has had orchiectomy by surgery
  * Serum PSA progression defined as two consecutive increases in PSA over a previous reference value, each measurement at least 1 week apart
* Progression after androgen receptor blockers (enzalutamide, apalutamide, or darolutamide) or androgen synthesis blockers (abiraterone acetate) or chemotherapy (docetaxel or cabazitaxel). There are no maximum number of prior therapies
* Progressive castration-resistant prostate cancer with two or more skeletal metastases identified by Tc-99m bone scintigraphy or prostate specific membrane antigen (PSMA) positron emission tomography (PET) scan
* Patients must have self-reported moderate to severe pain at trial entry (baseline weekly average "worst pain in the past 24-hours" scores of \>= 4 on an 11-point numeric rating scale \[NRS\], the Brief Pain Inventory - Short Form \[BPI-SF\] item #3 for worst pain)
* Patients must either currently employ regular (not occasional) analgesic medication use for cancer-related bone pain or have undergone treatment with external beam radiation therapy (EBRT) for bone pain within 4 weeks before starting study treatment
* Age \>= 18 years. Children \< 18 years of age are excluded from the study as the prevalence of prostate cancer is extremely rare in this age group
* Patients must have a life expectancy \>= 3 months
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Patients must have a serum PSA value \>= 1 ng/mL
* Absolute neutrophil count \>= 1,000/mcL
* Platelets \>= 100,000/mcL
* Hemoglobin \> 10.0 g/dL
* Total bilirubin =\< 2.5 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 5 x institutional ULN
* Creatinine =\< 1.7 mg/dL OR glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2
* Patients receiving bisphosphonates prior to enrollment can maintain bisphosphonate therapy throughout all or part of the study. The bisphosphonate may be stopped or started at the discretion of the investigator throughout the study (i.e., both treatment phase and follow-up). Injection of bisphosphonates should be done at least 2 hours before or after study drug administration
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better
* The effects of Sn-117m-DTPA on the developing human fetus are unknown. For this reason and because radionuclides are known to be teratogenic, male participants and their female partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her male partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of Sn-117m-DTPA administration
* Patients must be willing and able to comply with the protocol and agree to return to the hospital for follow-up visits and examinations
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Patients must not have visceral metastases (such as liver and lung) as assessed by abdominal/pelvic computed tomography (CT) or chest X-ray within 12 weeks before starting study treatment
* Patients must not have malignant lymphadenopathy exceeding 3 cm in short-axis diameter
* Patients must not have imminent or established spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI)
* Patients who have had chemotherapy, immunotherapy, or external radiotherapy within 4 weeks prior to entering the study
* Patients must not have received systemic radiotherapy with radium-223, strontium-89, samarium-153, rhenium-186, or rhenium-188 for the treatment of bony metastases within 24 weeks before starting study treatment
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
* Patients must not have received any investigational agents within 4 weeks before starting study treatment, nor be scheduled to receive one during the planned treatment period
* Patients must not have unmanageable urinary incontinence
* Patients must not have had known non-pathological bone fractures within 2 months before starting study treatment
* Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Sn-117m-DTPA
* Patients must not have uncontrolled intercurrent illness, including:

  * Any uncontrolled infection
  * Grade 2 or greater motor or sensory neuropathy
  * Crohn's disease or ulcerative colitis
* Patients with psychiatric illness/social situations that would limit compliance with study requirements

Primary outcomes:
measure: Sustained Pain Response
timeFrame: Baseline to 16 weeks
Secondary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to 6 months post-therapy
measure: Tin Sn 117m Diethylenetriaminepentaacetic Acid (DTPA) (Sn-117m-DTPA) Activity
timeFrame: Up to 4 weeks after the first Sn-117m-DTPA administration
measure: Overall Response Rate
timeFrame: Up to 12 months after the first dose of tin Sn 117m DTPA
measure: Time to First Symptomatic Skeletal Event
timeFrame: Up to 12 months
measure: Overall Pain Response Rate
timeFrame: Within 12 weeks from first dose of Sn-117m-DTPA
measure: Duration of Pain Response
timeFrame: Time from the achievement of pain response (pain index =< 3) to the recurrence of pain (pain index >= 4), assessed up to 16 weeks
measure: Prostate Specific Antigen (PSA) Response Rates
timeFrame: Up to 28 weeks
measure: Alkaline Phosphatase (ALP) Response Rate
timeFrame: Up to 28 weeks
measure: Clinical Progression-free Survival
timeFrame: Time of study enrollment until disease progression, assessed up to 12 months
measure: Overall Survival
timeFrame: Time of the first study treatment until the date of death, assessed up to 12 months
Other outcomes:
measure: Tumor Genomic Alterations
timeFrame: Up to 12 months
measure: Changes in Systemic Inflammatory Markers and Immune Cell Populations
timeFrame: Baseline to after completion of treatment
measure: Polo-like Kinase 1 Immunohistochemistry
timeFrame: Up to 12 months
Locations:
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center LAO
name: Zin W Myint
role: PRINCIPAL_INVESTIGATOR
References:
citation: Myint ZW, El Khouli R, Lemieux B, Yan D, St Clair WH, Liu X, Kunos CA. A single arm phase II study of bone-targeted Sn-117 m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases. BMC Cancer. 2022 Apr 15;22(1):415. doi: 10.1186/s12885-022-09496-2.