A Phase 1 Study Evaluating the Safety, PK, and Clinical Effects of PT-112 in Subjects With Advanced Solid Tumors

Overview

About this study

The purpose of this study is to determine the maximum tolerated dose, and evaluate its safety, tolerability, preliminary clinical effects, and drug/body interactions.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Signed informed consent obtained before initiation of any study-specific procedures and treatment; Thymoma or thymic carcinoma based on morphology (WHO classification) and staging by revised Masaoka criteria (Nakagawa et al. 2003).
  • Documented objective, progressive disease after the most recent systemic therapy regimen (clinical progression alone is not sufficient).
  • Measurable disease, defined by the International Thymic Malignancy Interest Group (ITMIG), modified RECIST criteria (Benveniste et al. 2014).
  • Age ≥ 18 years.
  • ECOG Performance State 0 or 1.
  • Life expectancy > 3 months.
  • Adequate bone marrow, liver, kidney, and metabolic function, defined by:
    • ANC ≥ 1.5 x 10^9 /L (1500/µL);
    • Platelets ≥ 100 x 10^9 /L (100,000/µL);
    • Hb > 9 g/dL without transfusion or EPO dependency (within 7 days of assessment);
    • ALT and AST ≤ 2.5 x upper limit of normal (ULN) (≤ 5.0 x ULN if liver metastases are present);
    • Serum bilirubin V 1.5 x ULN (≤ 3.0 x ULN if liver metastases are present; total bilirubin ≤ 3.0 x ULN and direct bilirubin within the normal range in patients with well documented Gilbert Syndrome);
    • INR ≤ 2;
    • Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min for patients with creatinine levels > 1.5 x ULN;
    • Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L);
    • HbA1c ≤ 8%;
  • Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential;
  • Women of childbearing potential and men with partners of childbearing potential must take effective contraception for the study duration and at least 6 months after the last dose of study medication.

Exclusion Criteria:

  • Has known active CNS metastases and/or carcinomatous meningitis. However, patients with previously treated brain metastases may participate if they are stable (without evidence of progression by imaging for at least 4 weeks before the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids or are receiving stable low dose corticosteroid therapy (e.g., dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before the start of study treatment; Has acute or chronic liver disease, renal disease, or pancreatitis.
  • Has active autoimmune disease has required systemic treatment in the past 2 years (e.g., use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). However, myasthenia gravis that is adequately controlled (or has no evidence of neuropathy within 28 days of treatment) with only acetylcholinesterase inhibitor is allowed. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis; History of another invasive cancer within 3 years, with the exception that fully treated cancers with a remote probability of recurrence in the opinion of both the Medical Monitor and investigator.
  • History of another invasive cancer within 3 years, with the exception that fully treated cancers with a remote probability of recurrence in the opinion of both the Medical Monitor and investigator.
  • Has clinically significant peripheral vascular disease (ankle-brachial index < 0.90 at screening).
  • Has poorly controlled diabetes mellitus or steroid-induced diabetes mellitus.
  • Has uncontrolled hypertension (> 150/110 mmHg pre-treatment).
  • Has significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLCO, O2 saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates.
  • Has evidence of bleeding diathesis or coagulopathy (low dose anticoagulant therapy to maintain patency of vascular access device is allowed).
  • Any concurrent disease, infection, or comorbid condition that interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of data, in the opinion of both the investigator and Medical Monitor; Has known psychiatric or substance abuse disorders that might interfere with cooperation with the requirements of the trial.
  • Has received systemic anticancer medication ≤ 4 weeks (6 weeks of nitrosourea, mitomycin-c, or antibodies) before starting study drug or has not recovered to Grade ≤ 1 from side effects of therapy administered more than 4 weeks earlier.
  • Evidence of peripheral neuropathy of Grade ≥ 2 within 28 days before initiation of dosing.
  • Has undergone major surgery ≤ 4 weeks before starting study drug or has not recovered from side effects of earlier surgery.
  • Has received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks before starting study drug or has not recovered from side effects of earlier radiotherapy.
  • Known allergy or hypersensitivity to platinum-containing agents, or known intolerance to prior Pt-containing agent which, in the judgment of the Principal Investigator, precludes re-exposure to Ptcontaining agent.
  • Previous malignancy, except for non-squamous cell carcinoma of the skin or cured in situ cervical cancer of the uterine cervix unless the tumor was treated with curative intent more than 2 years before study entry.
  • Any cytotoxic chemotherapy within 21 days before initiation of study drug.
  • Any immunomodulatory drug therapy, anti-neoplastic hormonal therapy (unless dose has been stable for 3 months before Screening and will remain stable during the trial), immunosuppressive therapy, corticosteroids > 10 mg/day prednisone or equivalent (unless administered to prevent contrast material reactions during radiographic procedures), or growth factor treatment (e.g., erythropoietin) within 14 days before initiation of study drug.
  • Human immunodeficiency virus or acquired immunodeficiency syndrome-related illness.

Exclusion Criteria:

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Roxana Dronca, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Brian Costello, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Alan Bryce, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
.
CLS-20236303

Mayo Clinic Footer