Clinical trial NCT06982222: Testing the Safety of the Anti-cancer Drug, Sn-117m-DTPA, for Advanced Cancers That Have Spread to Bones
Official title: A First-in-Human Dose-Finding Phase I Study of Bone-targeted High Specific Activity Stannic-117m Pentatate (Sn-117m-DTPA) in Solid Tumors With Skeletal Metastases
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Anatomic Stage IV Breast Cancer AJCC v8
Metastatic Breast Carcinoma
Metastatic Lung Non-Small Cell Carcinoma
Metastatic Malignant Neoplasm in the Bone
Metastatic Prostate Adenocarcinoma
Stage IV Lung Cancer AJCC v8
Stage IVB Prostate Cancer AJCC v8
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2025-05-21
Enrollment: 24
Sex: ALL
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 I trial tests the safety, side effects and best dose of tin (Sn)-177m-diethylenetriaminepentaacetic acid (DTPA) and how well it works in treating prostate, breast or non-small cell lung cancer that has spread from where it first started (primary site) to the bones (bone metastases). Sn-117m-DTPA was originally tested in tumors that had spread to the bones to help reduce bone pain. The drug has been improved and is designed to send low-level radiation to tumors in the bone while being gentler on the bone marrow, where blood cells are made. Sn-117m-DTPA may be safe and tolerable, and may slow down or shrink tumors in patients with metastatic prostate, breast, or non-small cell lung cancer that has spread to the bones.

Detailed description: PRIMARY OBJECTIVE:

I. To assess the safety and tolerability of tin Sn 117m pentetate (Sn-117m- diethylenetriaminepentaacetic acid \[DTPA\]) per Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity by prostate-specific membrane antigen (PSMA) positron emission tomography (PET) response criteria for prostate cancer and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) response criteria for breast and non-small cell lung cancers.

II. 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 (Scher et al., 2016).

III. To measure changes and time to progression in serum prostate-specific antigen (PSA) (in prostate cancer patients only), and bone-specific alkaline phosphatase (bALK PHOS) (in all patients).

IV. To evaluate 2-year progression-free survival (PFS) and overall survival (OS) rates.

V. To characterize the biodistribution and dosimetry of high specific activity Sn-117m-DTPA in the treated population.

OUTLINE: This is a dose-escalation study followed by a dose-expansion study.

Patients receive Sn-117m-DTPA intravenously (IV) over 10 minutes on day 1 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo urine and blood sample collection, PET/computed tomography (CT) and single photon emission computed tomography (SPECT)/CT throughout the study. Additionally, prostate cancer patients undergo technetium TC-99m (Tc-99m) bone scan at baseline and PSMA PET/CT throughout the study.

After completion of study treatment, patients are followed up every 6 months until death.

Eligibility criteria: Inclusion Criteria:

* Histologically documented prostate, breast, or non-small cell lung cancer (NSCLC)
* Metastatic disease in bone only (patients with visceral disease, cutaneous disease or malignant lymph nodes \> 3 cm in largest diameter are not eligible)
* Documented disease progression (1 or more new bone lesion or enlargement of existing bone lesion, identified by Tc-99m bone scintigraphy or CT scan, magnetic resonance imaging \[MRI\], fludeoxyglucose F-18 \[FDG\] PET CT scan or PSMA PET CT scan)
* Must have progression on at least one line of standard of care systemic therapy. There are no maximum number of prior therapies
* Patients with prostate cancer

  * Patients with prostate adenocarcinoma, their disease must be characterized as: must have prior bilateral orchiectomy or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (\< 50 ng/dL or \< 1.7 nmol/L)
  * Serum PSA progression, defined as two consecutive increases in PSA over a previous reference value, each measurement at least one week apart or, PSA progression ≥ 25% after 12 weeks of current standard of care (SOC) therapy (Scher et al., 2016)
  * Patients must have a baseline positive PSMA-PET scan. Patients must have progressed on at least one line of hormone therapy: Androgen receptor signaling inhibitors (ARSIs) therapy such as enzalutamide, apalutamide, darolutamide, or androgen synthesis blockers (abiraterone acetate). There are no minimum number of prior hormone therapies
  * Progression after chemotherapy (docetaxel or cabazitaxel) in patients who were chemotherapy candidates is allowed. However, prior chemotherapy is not required
  * Progression after a prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy (for example: lutetium-177 vipivotide tetraxetan \[Pluvicto\]) is allowed but not required
  * Allowed to have received one prior cytotoxic chemotherapy treatment and one radiopharmaceutical therapy treatment OR no more than two cytotoxic chemotherapy treatments (for patients who have not received a prior radiopharmaceutical therapy treatment)
* Patients with breast cancer

  * Patients with any estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2) receptor status are eligible
  * Patients with hormone-receptor positive disease should have progressed on at least one or more prior line(s) of SOC anti-estrogen therapy and a cyclin-dependent kinase (CDK)4/6 inhibitor (except if patient had a contraindication or intolerable toxicity with the use of these agents)
  * Patients with HER2 positive disease should have progressed on at least one or more line(s) of SOC anti-HER2 therapy.
  * Patients with triple negative disease should have progressed on at least one more line(s) of SOC chemotherapy
  * Previous radiation and chemotherapy are allowed
* Patients with non-small cell lung cancer (NSCLC)

  * Patients with NSCLC should have progressed on at least one or more prior line(s) of SOC therapy, including chemotherapy and/or immunotherapy or targeted therapy if they qualify
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of Sn-117m-DTPA in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
* Absolute neutrophil count ≥ 1,000/mcL
* Platelets ≥ 75,000/mcL
* Hemoglobin \> 9 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 must be taking a bone health agent (bisphosphonates or denosumab) for at least one (1) month prior to enrollment
* 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 treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
* 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 II or better
* The effects of Sn-117m-DTPA on the developing human fetus are unknown. For this reason and because radionucleotides are known to be teratogenic, male participants and their female partners of childbearing potential 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. A woman of childbearing potential is a premenopausal female capable of becoming pregnant. Should a woman of childbearing potential become pregnant or suspect she is pregnant while her male partner is participating in this study, she should inform her treating physician immediately. Both men and women of childbearing potential treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months after completion of Sn-117m-DTPA administration. For prostate cancer patients, androgen deprivation therapy is considered adequate contraception
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign if the patient is physically (not mentally) not capable of signing

Exclusion Criteria:

* Patients who have not recovered from reversible 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 or 5 half-lives, whichever is shorter, before starting study treatment, nor be scheduled to receive one during the planned treatment period
* 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 imminent or established spinal cord compression, pathological fracture in weight bearing bones, or bone lesion with soft tissue component unless treated as appropriate with radiation and/or surgery before starting on this study
* Patients must not have received prior systemic radiotherapy with strontium-89, samarium-153, rhenium-186, rhenium-188, or radium-223 dichloride (Xofigo) for the treatment of bony metastases. Prior systemic radiopharmaceutical therapy with lutetium Lu 177 vipivotide tetraxetan (Pluvicto) is permitted, but last treatment must be at least six weeks prior to starting study treatment due to the concern of bone marrow suppression
* Patients must not have unmanageable urinary incontinence
* Pregnant women are excluded from this study because Sn-117m-DTPA is a radionucleotide with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Sn-117m-DTPA, breastfeeding should be discontinued if the mother is treated with Sn-117m-DTPA

Primary outcomes:
measure: Frequency of dose-limiting toxicities
timeFrame: Up to completion of 1 cycle (cycle length = 56 days)
measure: Frequency of adverse events
timeFrame: Up to 30 days after last dose of study treatment
Secondary outcomes:
measure: Tumor response
timeFrame: Up to 2 years
measure: Time to first symptomatic skeletal event
timeFrame: Up to 2 years
measure: Changes in serum PSA (prostate cancer patients only)
timeFrame: At baseline, days 44-56 of cycle 1, and days 30-56 of cycle 2
measure: Time to progression in serum PSA (prostate cancer patients only)
timeFrame: At baseline, days 44-56 of cycle 1, and days 30-56 of cycle 2
measure: Changes in bone-specific alkaline phosphatase levels (all patients)
timeFrame: At baseline, days 44-56 of cycle 1, and days 30-56 of cycle 2
measure: Progression-free survival
timeFrame: From the first study treatment until the date of PERCIST definition of progression for breast and non-small cell lung cancers and PSMA PET/CT definition of progression for prostate cancer, assessed up to 2 years
measure: Overall survival
timeFrame: From the first study treatment until the date of death, assessed up to 2 years
measure: Biodistribution and dosimetry of high specific activity tin (Sn)-117m-diethylenetriaminepentaacetic acid (DTPA)
timeFrame: On days 1, 2, 4, and 43 of cycle 1
Other outcomes:
Locations:
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center LAO
name: Zin W Myint
role: PRINCIPAL_INVESTIGATOR
References: