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

Learn more about:
Related Clinical Trial
Retrospective Register for Uveal Melanoma Proof of Concept of TBio-4101, Lymphodepleting Chemo, IL-2 for Relapsed/Refractory Melanoma Pilot Trial of Autologous Tumor Infiltrating Lymphocytes (LN-144) for Patients With Metastatic Uveal Melanoma A Study of TBio-4101 (TIL) and Pembrolizumab in Patients With Advanced Solid Tumors Sitravatinib and Tislelizumab in Patients With Metastatic Uveal Melanoma With Liver Metastases. Olaparib in Combination With Pembrolizumab for Advanced Uveal Melanoma Adjuvant Melatonin for Uveal Melanoma Targeted Alpha Particle Radiotherapy for Metastatic Uveal Melanoma Olaparib in Unresectable/Metastatic Melanoma With BRCA1/2 Prospective Registration Of Patient Data and Quality of Life in Eye Melanoma Patients Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (Including Ocular Melanoma) The Role of Genetic Mutations and of Circulating mRNAs in Uveal Melanoma A Study of Concurrent Stereotactic Body Radiotherapy With Ipi and Nivo in Metastatic Uveal Melanoma Single Arm Trial of Tumor-Treating Fields in Combination With Nivolumab and Ipilimumab in Metastatic Uveal Melanoma Managed Access Program Supporting Patient Access to Tebentafusp Efficacy of Spartalizumab Across Multiple Cancer-types in Patients With PD1-high mRNA Expressing Tumors Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome A Study of APG-115 in Combination With Pembrolizumab in Patients With Metastatic Melanomas or Advanced Solid Tumors Early Integration of Supportive Care Into Standard Oncology Care for Metastatic Uveal Melanoma Patients Defactinib (VS-6063) Combined With VS-6766 in Patients With Metastatic Uveal Melanoma Study of PAC-1 and Entrectinib for Patients With Metastatic Uveal Melanoma A Prospective Natural History Study in Uveal Melanoma Uveal Melanoma and Brachytheraphy: Long-term Outcomes. A Study of RO7293583 in Participants With Unresectable Metastatic Tyrosinase Related Protein 1 (TYRP1)-Positive Melanomas Study to Evaluate the Safety of IMM-01 in Patients With Advanced Solid Tumours Isolated Hepatic Perfusion in Combination With Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastases Study of Safety and Tolerability of BCA101 Alone and in Combination With Pembrolizumab in Patients With EGFR-driven Advanced Solid Tumors Follow-up of Patients With Uveal Melanoma Adapted to the Risk of Relapse (SALOME) Phase 2 Trial of AU-011 Via Suprachoroidal Administration With a Dose Escalation and Randomized, Masked Dose Expansion Designed to Evaluate Safety and Efficacy of AU-011 in Subjects With Primary Indeterminate Lesions and Small Choroidal Melanoma Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies Cabozantinib-S-Malate Compared With Temozolomide or Dacarbazine in Treating Patients With Metastatic Melanoma of the Eye That Cannot Be Removed by Surgery Epacadostat and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma Sargramostim, Vaccine Therapy, or Sargramostim and Vaccine Therapy in Preventing Disease Recurrence in Patients With Melanoma That Has Been Removed By Surgery A Study of PLX2853 in Advanced Malignancies. Combined PET/CT Imaging for the Early Detection of Ocular Melanoma Metastasis Compared to CT Scanning Alone A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001) TTT Versus TTT and Triamcinolone to Decrease Exudation in Choroidal Melanoma After Proton Beam Therapy C7R-GD2.CART Cells for Patients With Relapsed or Refractory Neuroblastoma and Other GD2 Positive Cancers (GAIL-N) Genetic Predictors of Efficiency and Safety of ICIs in Patients With Different Malignancies (ICIPRESIST-0519) Treatment Of Radiation Retinopathy Trial Temozolomide or Selumetinib in Treating Patients With Metastatic Melanoma of the Eye Intravitreal Ranibizumab for the Prevention of Radiation Maculopathy Following Plaque Radiotherapy Ph 1 Study in Subjects With Tumors Requiring Arginine to Assess ADI-PEG 20 With Pemetrexed and Cisplatin Study in Subjects With Small Primary Choroidal Melanoma Study Multicentre Evaluating the Effectiveness and Toxicity Sorafenib (Nexavar®) in Adult Patients With Uveal Melanoma and Metastatic Dissemination Trial of AEB071 in Combination With BYL719 in Patients With Melanoma Halt Growth of Liver Tumors From Uveal Melanoma With Closure of Liver Artery Following Injection of GM-CSF Vorinostat in Treating Patients With Metastatic Melanoma of the Eye Radiation Therapy in Preventing Liver Metastases in Patients With Uveal Melanoma Who HaveMonosomy 3 or DecisionDx Class 2 Disease and Are More Likely to Develop Liver Metastases 5 Year Registry Study to Track Clinical Application of DecisionDx-UM Assay Results and Associated Patient Outcomes Hypofractionated Stereotactic Linear Accelerator Radiotherapy of Uveal Melanoma Study Evaluating Single and Repeated Intravitreal Doses of ICON-1 in Patients With Uveal Melanoma Pembrolizumab in Treating Patients With Advanced Uveal Melanoma Vascular Response to Brachytherapy Using Functional OCT Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma SIR-Spheres® 90Y Microspheres Treatment of Uveal Melanoma Metastasized to Liver Glembatumumab Vedotin in Treating Patients With Metastatic or Locally Recurrent Uveal Melanoma Dexamethasone Intravitreal Implant for Treatment of Macular Edema After Plaque Radiotherapy of Uveal Melanoma Stereotactic Body Radiation Therapy and Aflibercept in Treating Patients With Uveal Melanoma Endoresection of the Tumor Scar or Transpupillary Thermotherapy for the Treatment of Large Uveal Melanomas (Endoresection-Laser) Durvalumab (MEDI4736) Plus Cediranib in Patients With Metastatic Uveal Melanoma A Phase Ib/II Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma Study of AntiCTLA4 in Patients With Unresectable or Metastatic Uveal Melanoma Tilting of Radioactive Plaques After Initial Accurate Placement for Treatment of Uveal Melanoma A Study of the Intra-Patient Escalation Dosing Regimen With IMCgp100 in Patients With Advanced Uveal Melanoma Trametinib With or Without GSK2141795 in Treating Patients With Metastatic Uveal Melanoma RAD001 (Everolimus) and Pasireotide (SOM230) LAR in Patients With Advanced Uveal Melanoma Safety & Activity of Controllable PRAME-TCR Therapy in Previously Treated AML/MDS or Metastatic Uveal Melanoma CAVATAK® and Ipilimumab in Uveal Melanoma Metastatic to the Liver (VLA-024 CLEVER) Comparison Between Fotemustin to Intensive Surveillance in Patients With High Risk Uveal Melanoma Dendritic Cells Plus Autologous Tumor RNA in Uveal Melanoma Study of Immunotherapy Plus ADI-PEG 20 for the Treatment of Advanced Uveal Melanoma New Biopsy Technique for Uveal Melanoma Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) Safety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients Influence of Oral Treatment With Citicoline for the Prevention of Radiation Optic Neuropathy in Patients Treated for Uveal Melanomas With Proton Beam Therapy Intermittent Selumetinib for Uveal Melanoma Transarterial Radioembolisation in Comparison to Transarterial Chemoembolisation in Uveal Melanoma Liver Metastasis A Phase I Study of LXS196 in Patients With Metastatic Uveal Melanoma. Evaluation Interest of the Circulating Tumor DNA Dosage in Patient With Hepatic Metastatic Uveal Melanoma Candidate to Complete Resection (ct DNA R0) Messenger Ribonucleic Acid (mRNA) Transfected Dendritic Cell Vaccination in High Risk Uveal Melanoma Patients Study of the Activity of PD-1 Inhibitors in Metastatic Uveal Melanoma A Study of Sorafenib in Patients With Chemonaive Metastatic Uveal Melanoma Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy Trial of Nivolumab in Combination With Ipilimumab in Subjects With Previously Untreated Metastatic Uveal Melanoma Vorinostat in Patients With Class 2 High Risk Uveal Melanoma Yttrium90, Ipilimumab, & Nivolumab for Uveal Melanoma With Liver Metastases A Phase II Study of BVD-523 in Metastatic Uveal Melanoma Assessing the Clinical Effectiveness of Serum Biomarkers in the Diagnosis of Metastatic Uveal Melanoma Treatment With Intravitreal Avastin for Large Uveal Melanomas

Brief Title

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

Official Title

Phase 1B/2 Study of PAC-1 and Entrectinib for Patients With Metastatic Uveal Melanoma

Brief 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.

Study Phase

Phase 1/Phase 2

Study Type


Primary Outcome

Phase 1b: Determine maximum tolerated dose (MTD) of PAC-1

Secondary Outcome

 Incidence and severity of adverse events


Uveal Melanoma



Study Arms / Comparison Groups

 Study Treatment Arm
Description:  Phase 1b will determine the MTD of PAC-1 in combination with entrectinib. Study treatment will include: PAC-1 will be taken orally on Days 1-21 and Entrectinib will be taken orally on Days 1-28 of each 28-day cycle. Treatment will continue until disease progression (based on RECIST 1.1 criteria), unacceptable toxicity, subject withdrawal of informed consent, or subject death either from progression of disease, the therapy itself, or from other causes.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

January 11, 2021

Completion Date

August 2023

Primary Completion Date

August 2, 2022

Eligibility Criteria

        Inclusion Criteria

          1. 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.

          2. Age ≥ 18 years at the time of consent.

          3. Histologically or cytologically confirmed metastatic uveal melanoma. Staging per AJCC
             manual edition 8.

          4. One or more lesions that could be accurately measured using Response Evaluation
             Criteria in Solid Tumors (RECIST) 1.1.

          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (Appendix 1).

          6. 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

          7. Subjects must have archival tissue (metastatic disease preferred) available or undergo
             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.

          8. Prior therapy is allowed but must have been completed 21 days prior to initiation of
             protocol therapy and all toxicities must be < Grade 2.

          9. Palliative radiation must have been completed 2 weeks prior to the initiation of study

         10. 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

         11. 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.

         12. 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

         13. 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.

         14. The participant is capable of understanding and complying with the protocol and has
             signed informed consent document.

        Exclusion Criteria

          1. Peripheral sensory neuropathy Grade ≥ 2 (per CTCAE v5.0).

          2. Active gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short
             gut syndrome) or other malabsorption syndromes that would reasonably impact drug

          3. Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          4. 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.

          5. 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.

          6. 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.

          7. History of uncontrolled seizures.

          8. History of ataxia.

          9. Allergies and adverse drug reaction: History of allergy to study drug components.

         10. 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.

         11. History of recent (within the past 3 months) symptomatic congestive heart failure or
             ejection fraction ≤ 50% observed during screening for the study.

         12. History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval >
             450 milliseconds from ECGs performed at least 24 hours apart).

         13. History of additional risk factors for torsades de pointes (e.g., family history of
             long QT syndrome).

         14. 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.

         15. Active infection requiring intravenous systemic treatment.

         16. Serious non-healing wound/ulcer/bone fracture within 28 days prior to registration.

         17. Known uncontrolled, symptomatic brain metastasis or cranial epidural disease.

         18. Known additional malignancies which require systemic treatment.

         19. Inability to swallow intact tablets.

         20. 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.




18 Years - N/A

Accepts Healthy Volunteers



Arkadiusz Dudek, MD, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Arkadiusz Z. Dudek, MD


 HealthPartners Regions Cancer Care and Frauenshuh Cancer Care Centers

Study Sponsor

Arkadiusz Dudek, MD, PhD, Principal Investigator, Health Partners Institute

Verification Date

November 2022