Using PT-112 to treat thymoma and thymic carcinoma

A Phase II, Open-Label Trial of PT-112 in Subjects With Thymoma and Thymic Carcinoma

This study is testing a new treatment called PT-112 to see if it can help shrink tumors in patients with thymoma and thymic carcinoma who have already tried other chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 53 (estimated)
• Ages: 18 Years to 120 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT05104736 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy of PT-112, a metallo-pyrophosphate conjugate, in patients with recurrent thymoma and thymic carcinoma who have previously undergone platinum-based chemotherapy. The study aims to determine the objective response rate of PT-112 in shrinking tumors, utilizing a single-arm, open-label design with two cohorts. Participants will receive PT-112 through infusion in 28-day cycles, with assessments including medical history reviews, physical exams, and imaging tests to monitor disease progression. The trial seeks to provide a new therapeutic option for patients with limited treatment choices.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed unresectable thymoma or thymic carcinoma who have experienced disease progression after platinum-based chemotherapy.

Not a fit: Patients with thymoma or thymic carcinoma who have not received prior platinum-based chemotherapy or have resectable disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for patients with recurrent thymoma and thymic carcinoma, potentially improving their outcomes.

How similar studies have performed: While there are no approved drugs for recurrent thymoma and thymic carcinoma, PT-112 has shown promise in previous clinical evaluations, suggesting potential efficacy in this patient population.

Eligibility criteria

* INCLUSION CRITERIA:
* Participants must have histologically confirmed thymoma or thymic carcinoma.
* Participants should have received at least one prior line of platinum-based chemotherapy. For participants who have refused cytotoxic chemotherapy, a rationale for refusal to receive standard first-line therapy will be captured in the case report form and the medical record. Progressive disease must be documented prior to study entry and participants must have advanced, unresectable disease that is not amenable to surgical resection.
* Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
* Participants must be aged \>=18 years.
* ECOG performance status \<=1.
* Participants must have adequate organ and marrow function as defined below:

  * absolute neutrophil count \>= 1,500/mm3 OR \>= 1.5 x 10(9)/L
  * platelets \>=100,000/mm3 OR (Bullet) 100 x 10(9)/L
  * hemoglobin \>= 9g/dL (may have been transfused, at least 7 days prior)
  * total bilirubin \<= 1.5 x the upper limit of normal range (ULN)
  * AST(SGOT)/ALT(SGPT) \<= 2.5 x ULN OR \<= 5 x ULN for participants with documented metastatic disease to the liver
  * creatinine \<= 1.5x ULN OR:
  * creatinine clearance \>= 60 mL/min/1.73 m2 calculated by calculated using eGRF in the clinical lab
* Negative serum or urine pregnancy test at screening for individuals of childbearing potential (IOCBP). NOTE: IOCBP is defined as any individual who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal. Absence of pregnancy must be demonstrated unless there is proven menopause (age \>= 50 years and last menarche \>= 3 years, or documented menopausal sex hormone profile, or surgical castration) at screening.
* Participants must not become pregnant or start breast feeding during the study. Breastfeeding should be discontinued if the mother is treated with PT-112.
* Individuals of child-bearing potential and those that can father children with a sexual partner of childbearing potential must use medically effective contraception during the study and for 6 months after the last dose of study medication.
* Participants with previously treated brain or CNS metastases are eligible provided that the participant has recovered from any acute side effects of radiotherapy and does not require treatment with steroids, and any whole brain radiation therapy was completed at least 2 weeks prior to initiation of study therapy.
* Ability of participant to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

* History of allergic reactions attributed to compounds of similar chemical or biologic composition to PT-112. Since there is no definitive list of compounds of similar chemical or biologic composition to PT-112, the principal investigator if in doubt, will report known allergies to the pharmacist to make a determination as to whether it is safe to enroll a participant.
* Concurrent treatment with a non-permitted drug.
* Concurrent anticancer treatment within 14 days before initiation of study therapy (includes radiotherapy; however, palliative bone-directed radiotherapy is permitted).
* Major surgery within 14 days before enrollment (excluding prior diagnostic biopsy).
* Concurrent systemic therapy with immunosuppressive agents within 14 days (or 5 half-lives of a drug, whichever is shorter) before initiation of study therapy.
* Use of hormonal agents for anti-cancer therapy within 14 days before initiation of study therapy; or use of any investigational drug within 14 days before initiation of study therapy.
* History of previous malignant disease within the last 2 years with the following exceptions: basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of the breast, papillary or follicular thyroid carcinoma, and non-muscle invasive bladder cancer.
* Active infection requiring systemic therapy or significant acute or chronic infections including, among others:

  * Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
  * Known history of testing positive for HIV or known acquired immunodeficiency syndrome with a detectable viral load. However, participants with HIV who have an undetectable viral load and are on stable doses of Highly Active Antiretroviral Therapy (HAART) can be screened for the study.
* Persisting toxicity related to prior therapy (NCI CTCAE v. 5 Grade \> 1) with the exception of, alopecia, sensory neuropathy Grade \<= 2 and hearing loss Grade \<=2.
* Known alcohol or drug abuse.
* Uncontrolled intercurrent illness including, but not limited to the following:

  * Cardiovascular: SYMPTOMATIC congestive heart failure, unstable angina pectoris or cardiac arrhythmia, either active or within the past 6 months
  * Respiratory: Pneumonitis or Idiopathic pulmonary fibrosis (not radiation-associated fibrosis), either active or within the past 6 months
  * Gastrointestinal: Immune colitis or inflammatory bowel disease, either active or within the past 6 months
  * Hematological: Bleeding diathesis or major bleeding events, either active or within the past 6 months
  * Other: psychiatric illness/social situations that would limit compliance with study requirements, including active suicidal ideation or behavior, either active or within the past 12 months
* Administration of live vaccines within 4 weeks prior to treatment. COVID-19 vaccines are permitted at screening.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Arun Rajan, M.D. — National Cancer Institute (NCI)
• Study coordinator: Shannon G Swift, R.N.

Conditions Thymic Epithelial Tumor; Recurrent Thymoma; Thymic Cancer; metallo-pyrophosphate; immunogenic cell death; osteotropism; damage-associated molecular patterns; Peripheral Neuropathy