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

Plain English Summary

Testing the Safety of the Anti-cancer Drug, Sn-117m-DTPA, for Advanced Cancers That Have Spread to Bones is a Phase 1 clinical trial sponsored by National Cancer Institute (NCI) studying 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. This trial is testing a new drug called Sn-117m-DTPA, which is designed to deliver radiation directly to cancer that has spread to the bones. It is for patients with advanced prostate, breast, or non-small cell lung cancer that has spread only to the bones. Participation involves receiving the study drug and undergoing regular tests, including scans and blood draws. Alternative treatments may include other cancer therapies or supportive care for bone pain. The trial aims to enroll 24 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with advanced prostate, breast, or non-small cell lung cancer that has spread only to the bones. Patients must have had their cancer progress after at least one prior treatment. Specific requirements vary based on cancer type, including prior treatments and specific test results (like PSMA-PET scans for prostate cancer). Patients with cancer spread to other organs (besides bones) or very large lymph nodes are not eligible. This trial is studying 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, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures will tell us how often patients experience dose-limiting side effects and any adverse events, helping to determine the safest dose of the new drug. The specific primary outcome measures are: Frequency of dose-limiting toxicities (Up to completion of 1 cycle (cycle length = 56 days)); Frequency of adverse events (Up to 30 days after last dose of study treatment). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial explores a new way to treat bone metastases by delivering radiation directly to the cancer in the bone, potentially reducing pain and side effects compared to traditional treatments. This research targets 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, where improved treatment options are needed.

Investor Insight

This Phase 1 trial is an early step in evaluating a novel targeted radiopharmaceutical, indicating potential for a new treatment option in a significant oncology market, though approval probability is Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for your specific cancer and if you meet all the eligibility requirements. Be prepared for regular clinic visits for drug administration, scans, and blood tests. Understand that this is a dose-finding study, meaning the dose of the drug may be adjusted during the trial. The trial is being conducted at multiple sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 24 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo urine and blood sample collection
• PROCEDURE: Bone Scan — Undergo technetium TC-99m bone scan
• PROCEDURE: Computed Tomography — Undergo PET/CT, SPECT/CT and PSMA PET/CT
• PROCEDURE: Positron Emission Tomography — Undergo PET/CT
• PROCEDURE: PSMA PET Scan — Undergo PSMA PET/CT

Primary Outcomes

• Frequency of dose-limiting toxicities (Up to completion of 1 cycle (cycle length = 56 days))
• Frequency of adverse events (Up to 30 days after last dose of study treatment)

Secondary Outcomes

• Tumor response (Up to 2 years)
• Time to first symptomatic skeletal event (Up to 2 years)
• Changes in serum PSA (prostate cancer patients only) (At baseline, days 44-56 of cycle 1, and days 30-56 of cycle 2)
• Time to progression in serum PSA (prostate cancer patients only) (At baseline, days 44-56 of cycle 1, and days 30-56 of cycle 2)
• Changes in bone-specific alkaline phosphatase levels (all patients) (At baseline, days 44-56 of cycle 1, and days 30-56 of cycle 2)

Full 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

Frequently Asked Questions

Related Conditions

• Prostate Cancer
• Breast Cancer
• Lung Cancer (Non-Small Cell)
• Bone Metastases
• Skeletal Metastases
• Metastatic Cancer
• Stage IV Cancer
• Oncology
• Radiopharmaceuticals
• Targeted Therapy

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