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

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Not yet recruiting
CT.gov ID
NCT05104736
Collaborator
(none)
53
Enrollment
1
Location
1
Arm
43.2
Anticipated Duration (Months)
1.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
53 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Open-Label Trial of PT-112 in Subjects With Thymoma and Thymic Carcinoma
Anticipated Study Start Date :
Nov 24, 2021
Anticipated Primary Completion Date :
Jun 30, 2025
Anticipated Study Completion Date :
Jun 30, 2025

Arms and Interventions

ArmIntervention/Treatment
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

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

Outcome Measures

Primary Outcome Measures

  1. overall response rate (ORR) [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

Secondary Outcome Measures

  1. safety of PT-112 [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

  2. duration of response (DOR) [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

  3. progression-free survival (PFS) [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

  4. overall survival (OS) [during treatment and then every 3 months]

    time from the date of start of treatment until death from any cause

  5. overall response rate (ORR) based on ITMIG modified RECIST (ITMIG) [start of the treatment until disease progression/recurrence]

    best overall response is the best response recorded per ITMIG modified RECIST criteria

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
  • 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 and sensory neuropathy 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

  • Participants who have received vaccination against COVID-19 within 14 days before enrollment.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1National Institutes of Health Clinical CenterBethesdaMarylandUnited States20892

Sponsors and Collaborators

  • National Cancer Institute (NCI)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT05104736
Other Study ID Numbers:
  • 10000317
  • 000317-C
First Posted:
Nov 3, 2021
Last Update Posted:
Nov 19, 2021
Last Verified:
Nov 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by National Cancer Institute (NCI)
Additional relevant MeSH terms:

Study Results

No Results Posted as of Nov 19, 2021