Study of PAC-1 and Entrectinib for Patients With Metastatic Uveal Melanoma

  • STATUS
    Recruiting
  • End date
    Jan 25, 2024
  • participants needed
    38
  • sponsor
    Arkadiusz Z. Dudek, MD
Updated on 25 March 2022

Summary

Single arm study with dose escalation Phase Ib cohort followed by a Phase II cohort. PAC-1 (PO) will be given daily on Days 1 through 21 of each cycle (28-day cycle). Entrectinib (PO) will be given daily on Days 1 through 28 of each cycle. Response will be evaluated after every 2 cycles. Treatment will continue until disease progression based on RECIST criteria or intolerable toxicity.

Details
Condition Uveal Melanoma
Treatment Entrectinib, PAC-1
Clinical Study IdentifierNCT04589832
SponsorArkadiusz Z. Dudek, MD
Last Modified on25 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. Patients must be willing and able to provide written informed consent for this trial
Age ≥ 18 years at the time of consent
Histologically or cytologically confirmed metastatic uveal melanoma. Staging per AJCC manual edition 8
One or more lesions that could be accurately measured using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (Appendix 1)
Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 14 days prior to registration
Leukocytes ≥ 2,000 µ/l
Absolute Neutrophil Count (ANC) ≥ 1,500 K/mm3
Platelets ≥ 100,000/µl
Hemoglobin (Hgb) ≥ 9 g/dL
Serum Creatinine ≤ 1.5 x ULN
Calculated creatinine clearance ≥ 40 mL/min
Total Bilirubin ≤ 1.5 mg/dL
Aspartate aminotransferase (AST) ≤ 2.5 × ULN
Alanine aminotransferase (ALT) ≤ 2.5 × ULN
Alkaline Phosphatase ≤ 2.5 × ULN
Partial Thromboplastin Time (PTT) < 1.5 × ULN
Subjects must have archival tissue (metastatic disease preferred) available or undergo
Prior therapy is allowed but must have been completed 21 days prior to initiation of protocol therapy and all toxicities must be < Grade 2
a biopsy prior to Cycle 1 Day 1 of treatment. Subjects that do not have
archival tissue or cannot undergo a biopsy are not eligible for the study
Palliative radiation must have been completed 2 weeks prior to the initiation of study therapy
Patient with known brain metastases must have been treated at least 2 weeks prior to enrollment, be asymptomatic from brain metastases, stable on brain imaging, and not be receiving a supra-physiologic dose of steroids (>10 mg prednisone daily or equivalent)
Women must not be pregnant or breastfeeding. All women of childbearing potential (WOCBP) must have a blood human chorionic gonadotrophin (hCG) test or urine hCG test within 2 weeks prior to registration to rule out pregnancy
Women of childbearing potential (WOCBP) must agree to use contraception as outlined in the protocol from the time of informed consent, during the study and for 3 months after the last dose of study drug(s). Abstinence from heterosexual intercourse is an acceptable form of contraception. Women of childbearing potential are those who have not been surgically sterilized or have not been free of menses >1 year
Male patients who are sexually active with WOCBP must agree to use contraception as outlined in the protocol from the time of initiation of study treatment, during the study and for 3 months after the last dose of study drug(s). Abstinence from heterosexual intercourse is an acceptable form of contraception
The participant is capable of understanding and complying with the protocol and has signed informed consent document

Exclusion Criteria

Active gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably impact drug absorption
Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
Has known active Hepatitis B or C. Active Hepatitis B is defined as a known positive HBsAg result. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay. For patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg), the patient is only eligible if they are negative for HBV DNA
Peripheral sensory neuropathy Grade ≥ 2 (per CTCAE v5.0)
Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis. NOTE: Radiation-induced lung disorders are not included in this exclusion criterion
History of retinal pigmented epithelial detachment, central serous retinopathy, or retinal vein occlusion in the unaffected eye; or intraocular pressure 21 mmHg or uncontrolled glaucoma (irrespective of intraocular pressure) in the unaffected eye
History of uncontrolled seizures
History of ataxia
Allergies and adverse drug reaction: History of allergy to study drug components
Thromboembolic events requiring therapeutic anticoagulation. Concomitant anticoagulation with oral anticoagulants (warfarin, direct thrombin or factor Xa inhibitors), platelet inhibitors (e.g. Clopidogrel, high dose aspirin) is prohibited. Low-dose aspirin (<100 mg/day), low-dose warfarin (<1 mg/day) and prophylactic low molecular weight heparin (LMWH) or similar agent are permitted
History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds from ECGs performed at least 24 hours apart)
History of additional risk factors for torsades de pointes (e.g., family history of long QT syndrome)
Cardiovascular disorders including unstable angina pectoris, clinically-significant cardiac arrhythmias, myocardial infarction or stroke (including transient ischemic attack [TIA], or other ischemic event) within 6 months prior to registration
History of recent (within the past 3 months) symptomatic congestive heart failure or ejection fraction ≤ 50% observed during screening for the study
Active infection requiring intravenous systemic treatment
Serious non-healing wound/ulcer/bone fracture within 28 days prior to registration
Known uncontrolled, symptomatic brain metastasis or cranial epidural disease
Known additional malignancies which require systemic treatment
Inability to swallow intact tablets
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the sponsor-investigator
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