PT-112 in Subjects With Thymoma and Thymic Carcinoma

• ClinicalTrials.gov Identifier: NCT05104736
• Recruitment Status: Recruiting
• First Posted: November 3, 2021
• Last Update Posted: March 30, 2023
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Tracking Information

• First Submitted Date: November 2, 2021
• First Posted Date: November 3, 2021
• Last Update Posted Date: March 30, 2023
• Actual Study Start Date: April 6, 2022
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 2, 2021)

overall response rate (ORR) [ Time Frame: assessed every 8 weeks while on treatment and then every 3 months after that for a maximum of 8 years from the start of study ]

best overall response is the best response recorded per RECIST 1.1 criteria, from the start of the treatment until disease progression/recurrence

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 2, 2021)

• safety of PT-112 [ Time Frame: safety data routinely collected from initiation of study therapy through long term follow up ]
  type, frequency, and grade of events will be collected and reported as assessed per CTCAE criteria, version 5
• duration of response (DOR) [ Time Frame: assessed every 8 weeks while on treatment and then every 3 months ]
  time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented
• progression-free survival (PFS) [ Time Frame: assessed every 8 weeks while on treatment and then every 3 months ]
  time from date of start of treatment until time of disease relapse, disease progression, or death
• overall survival (OS) [ Time Frame: during treatment and then every 3 months ]
  time from the date of start of treatment until death from any cause
• overall response rate (ORR) based on ITMIG modified RECIST (ITMIG) [ Time Frame: start of the treatment until disease progression/recurrence ]
  best overall response is the best response recorded per ITMIG modified RECIST criteria

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PT-112 in Subjects With Thymoma and Thymic Carcinoma
• Official Title: A Phase II, Open-Label Trial of PT-112 in Subjects With Thymoma and Thymic Carcinoma

Brief Summary

Background:

There are no approved drugs to treat recurrent thymoma and thymic carcinoma. New therapies are needed for people with these cancers. Researchers want to see if the drug PT-112 can help. PT-112 kills cancer cells. It also helps the body s immune system fight cancer.

Objective:

To see if the study drug PT-112 can cause tumors to shrink.

Eligibility:

People ages 18 and older who have thymoma or thymic cancer and whose disease returned or progressed after treatment with at least one platinum-containing chemotherapy, or who have refused standard treatment.

Design:

Participants will be screened with:

Review of medical history and medications

Physical exam

Blood and urine tests

CT or MRI scans of parts of the body, including the brain

Participants will get PT-112 on days 1, 8, and 15 of 28-day cycles. They will get the drug by infusion through a catheter. The catheter is a small plastic tube put into a vein. On days they receive the drug, participants will have physical exams and blood and urine tests. They will have an ECG to test heart function on day 1 of each cycle.

Participants will have scans every 8 weeks.

Participants may choose to have tumor biopsies on day 1 of cycles 1 and 3. Biopsies may be guided by an ultrasound or CT scan.

Participants will continue treatment as long as they can handle the side effects and their disease does not get worse.

Participants will have follow-up visits 2 weeks and 4 weeks after they stop therapy. Then the study team will check on participants every 3 months for the rest of their life.

Detailed Description

Background

Platinum-based chemotherapy is the standard of care for advanced unresectable thymic epithelial tumors (TETs). However, more than half of these patients experience disease recurrence and require second-line therapy.

There are no approved drugs for treatment of recurrent thymoma and thymic carcinoma and new therapeutic options are needed for patients who have disease progression on or after platinum-containing therapy.

PT-112, a first-in-class metallo-pyrophosphate conjugate, offers a unique set of properties of both cellular interaction and molecular antitumor mechanisms, including resistance to DNA repair pathways and induction of immunogenic cell death.

PT-112 has been clinically proven to be safe and tolerable and has demonstrated efficacy.

Primary Objectives

To determine the objective response rate (ORR) based on RECIST criteria v1.1 to PT-112 in patients with relapsed or refractory TETs.

Eligibility

Participants >= age 18 years with histologically confirmed, unresectable thymoma or thymic carcinoma who have previously been treated with at least one platinum-containing chemotherapy regimen or must have refused cytotoxic chemotherapy.

Participants must have progressive and measurable disease

Adequate renal, hepatic and hematopoietic function

Design

This will be a single-arm, open-label study with two cohorts (cohort 1: thymoma; cohort 2: thymic carcinoma) to determine the clinical activity and safety of PT-112 in participants with relapsed or refractory TETs.

PT-112 will be administered intravenously on Days 1, 8 and 15 of a 28-day cycle at a dose of 360 mg/m2 until disease progression or development of intolerable adverse events.

For participants who develop intolerable toxicity at a dose of 360 mg/m2, two dose reductions will be permitted to 300 mg/m2 or 250 mg/m2 after resolution of adverse events to < grade 1 or baseline.

Toxicity will be assessed every cycle by CTCAE, version 5.0.

Tumor response will be assessed after completion of every other cycle (8 weeks) using RECIST criteria, version 1.1. Additionally, for participants with pleural dissemination tumor response will be assessed using International Thymic Malignancy Interest Group (ITMIG) modified RECIST criteria.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Thymic Epithelial Tumor
• Recurrent Thymoma
• Thymic Cancer

Intervention

Drug: PT-112

PT-112 will be administered intravenously on Days 1, 8 and 15 of a 28-day cycle at a dose of 360 mg/m2

Study Arms

Experimental: PT-112

PT-112 will be administered intravenously on Days 1, 8 and 15 of a 28-day cycle at a dose of 360 mg/m2 until disease progression, development of intolerable adverse events, or until 8 years after an individual participant has been on study

Intervention: Drug: PT-112

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 2, 2021): 53
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2025
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

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 109/L
  • platelets >=100,000/mm3 OR (Bullet) 100 x 109/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 females of childbearing potential (FOCBP). NOTE: FOCBP is defined as any female 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.
• Female participants must not become pregnant or start breast feeding during the study. Breastfeeding should be discontinued if the mother is treated with PT-112.
• Female participants of childbearing potential (i.e., without proven menopause, see above) and male participants 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Shannon G Swift, R.N.; (240) 858-3157; shannon.swift@nih.gov

Contact: Arun Rajan, M.D.; (240) 760-6236; rajana@mail.nih.gov

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05104736
• Other Study ID Numbers: 10000317; 000317-C
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request. All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.

• Current Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
• Original Responsible Party: Same as current
• Current Study Sponsor: National Cancer Institute (NCI)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Arun Rajan, M.D.; National Cancer Institute (NCI)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: March 28, 2023