RecruitingPhase 1

Safety and Tolerability of ²¹²Pb-DOTAM-GRPR1 in Adult Subjects With Recurrent or Metastatic GRPR-expressing Tumors

A Phase 1 Open-Label, First-in-human, Dose Escalation and Expansion Study to Determine the Safety, Tolerability, Dosimetry, Pharmacokinetics, and Preliminary Efficacy of 212Pb-DOTAM-GRPR1 in Adult Participants With Recurrent or Metastatic GRPR-expressing Tumors

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests ²¹²Pb-DOTAM-GRPR1 in people for the first time to learn about its safety, side effects, and how it moves through the body. It also looks for early signs that it works against cancer. It is for adults with certain cancers that have come back or spread and show GRPR, a protein targeted by the study drug.

A Phase 1 Open-Label, First-in-human, Dose Escalation and Expansion Study to Determine the Safety, Tolerability, Dosimetry, Pharmacokinetics, and Preliminary Efficacy of 212Pb-DOTAM-GRPR1 in Adult Participants with Recurrent or Metastatic GRPR-expressing Tumors

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be age 18 or older and able to sign a form agreeing to join the study.
  • Have an eligible advanced cancer: prostate cancer that resists hormone-lowering treatment; hormone-sensitive, HER2-negative breast cancer; colon or rectal cancer; cervical cancer; non-small-cell lung cancer; or glioblastoma, a brain cancer that has come back.
  • Have cancer that worsened after at least 2 treatments that work throughout the body. This rule does not apply to glioblastoma. People with prostate cancer must also have very low testosterone after surgery to remove the testicles or while taking hormone-lowering treatment.
  • Usually have at least one tumor that can be measured and shows the study target on a special scan. Prostate cancer in bone may qualify without a measurable soft-tissue tumor. Glioblastoma has separate scan rules.
  • Be fully active or able to walk and do light work. Some people with greater limits on activity may be approved.
  • Have blood tests showing enough healthy blood cells and acceptable liver, kidney, and pancreas test results.
  • If pregnancy is possible, follow the study’s birth control or no-sex rules during and after the study. After the last treatment dose, this lasts 7 months for women and 4 months for men. If only the scan drug is given, it lasts 10 days.
  • For glioblastoma: have a first or second return after standard treatment, including radiation finished at least 12 weeks before study treatment. Any surgery for its return must be at least 4 weeks before treatment, with recovery free of surgery-related problems. The tumor must show uptake on the study scan and contrast enhancement on MRI.

Who can't join

    Simplified for readability. The official criteria below are what the study team uses.

    Official eligibility criteria

    1. Adult participants (age ≥ 18 years old) with any of the following advanced or metastatic solid tumors (documented history of histologically confirmed diagnosis): 1. Metastatic castration-resistant prostate cancer (mCRPC) including neuroendocrine prostate cancer (NEPC) (enrolled only in SAD and MAD Q6W) 2. HR+/HER2- breast cancer (estrogen receptor/ER expression \>10% of tumor cell nuclei stain, regardless of progesterone receptor/PgR expression); HER2-negative including HER2-low (as per relevant ASCO/CAP guidelines) 3. Colorectal cancer 4. Cervical cancer 5. Non-small-cell lung cancer (NSCLC) 6. Recurrent glioblastoma (only enrolled in MAD Q4W cohorts) with evidence of recurrent disease (RD) demonstrated by disease progression using modified Response Assessment in Neuro-Oncology (RANO 2.0) criteria. Note: If surgery is performed for GBM recurrence, pre-surgery MRI will be used for confirmation of RD and residual and measurable disease post-surgery is not required but surgery must have confirmed the recurrence diagnosis by MRI. 2. Capable of giving signed informed consent 3. All participants must have progressed on at least 2 prior systemic therapies, except for recurrent GB 4. For participants with mCRPC: Prior orchiectomy and/or ongoing androgen deprivation therapy and a castrate level of serum testosterone (\<50 ng/dL or \<1.7 nmol/L) 5. Presence of at least 1 measurable lesion per RECIST 1.1 as assessed by the Investigator (not applicable for GBM). At least 1 identified measurable lesion must show GRPR uptake in 203Pb-DOTAM-GRPR1 SPECT/CT (uptake greater than that of the background) as assessed by the Investigator. 6. For participants with prostate cancer that do not have measurable soft tissue disease, 203Pb-DOTAM-GRPR1 uptake in bone lesions \> uptake in background is acceptable for eligibility. 7. Eastern Cooperative Oncology Group (ECOG) status 0-1. Participants with ECOG status of 2 may be approved on a case-by-case basis in discussion with the Sponsor. 8. Adequate bone marrow, hepatic, and renal function, as assessed by the following laboratory requirements: 1. White blood cell (WBC) ≥3000/ mm3 (≥ 3 x 109/L) 2. Absolute neutrophil count (ANC) ≥1500/mm3 (≥1.5 x 109/L) 3. Platelets ≥100,000/mm3 (≥ 100 x 109/L) 4. Hemoglobin (Hb) ≥9.0 g/dL 5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3x upper limit of normal (ULN) or ≤ 5 x ULN in the presence of liver metastases 6. Total bilirubin: ≤1.5 x ULN, except if documented history of Gilbert's disease who are eligible if total bilirubin ≤ 3 x ULN 7. Adequate renal function defined by creatinine clearance (CLCR) ≥ 60 mL/min calculated as follows: CLCR = eGFR in ml/min/1.73 m2 calculated by the Modified Diet in Renal Disease (MDRD) x participant body surface area (BSA) in m2 ÷ 1.73 8. Serum amylase and/or lipase ≤1.5 x ULN 9. For women of childbearing potential (WOCBP) and men with partners of childbearing potential: be willing to use highly effective methods of contraception or sexual abstinence, if part of participant's lifestyle, throughout the study and for 7 months for WOCBP, 4 months for men after the last \[212Pb\]Pb-DOTAM-GRPR1 administration or for 10 days following \[203Pb\]Pb-DOTAM-GRPR1 administration and participant is not proceeding to 212Pb-DOTAM-GRPR1 treatment, as outlined in protocol. Participants with Recurrent Glioblastoma: 10. Having first or second glioblastoma recurrence, after standard therapy that includes prior radiation therapy (RT) and at least 12 weeks from completion of RT prior to first administration of 212Pb-DOTAM-GRPR1. In case surgery has been performed for GBM recurrence, the surgery has to be completed at least 4 weeks prior to 212Pb-DOTAM-GRPR1 treatment start, with post-surgery recovery without any complications related to surgical procedure. 11. Presence of 203Pb-DOTAM-GRPR1 uptake by SPECT/CT scan in the tumor lesion(s). 12. Presence of Gadolinium enhancement in the MRI in the tumor lesion(s) shown at the time of diagnosis of tumor recurrence.

    Study sites (8)

    IA

    • University of Iowa Health Care · Iowa City, IA 52242David Bushness, MD · Principal investigatorMore trials in Iowa City

    IL

    KY

    MD

    NE

    • Nebraska Cancer Specialists (Midwest Cancer Center - Legacy) · Omaha, NE 68130Samuel Mehr, MD · Principal investigatorMore trials in Omaha
    • XCancer Omaha / Urology Cancer Center · Omaha, NE 68130 · Study contact · 402-697-2229Luke Nordquist, MD · Principal investigatorMore trials in Omaha

    PA

    • University of Pittsburg Medical Center (UPCM) · Pittsburgh, PA 15219Neeta Pandit Taskar, MD · Principal investigatorMore trials in Pittsburgh