TheranosticTrials.org

Clinical Trial · NCT03089606

Pembrolizumab TX-naive Distant Mets Melanoma and Use of (C11-AMT) PET at Baseline as Imaging Biomarker

Overview

Explore the association between intensity of 11C-methyl-L-tryptophan (C11-AMT) positron emission tomography (PET) at baseline, as measured by mean standardized uptake value (SUVmax) at each lesion, total tumor metabolic volume, measurement of intra-tumoral and inter-lesional heterogeneity, with objective response rate (ORR) at 12 weeks (as defined via RECIST 1.1) to pembrolizumab in patients with treatment-naïve metastatic melanoma.

Sponsor

UNC Lineberger Comprehensive Cancer Center

Phase

Phase 2

Contacts

Stergios Moschos, MD (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT03089606

Drug / Compound

methyl-L-tryptophan

Isotope(s):
Target(s):
  • Amino Acid Transport
Ligand Class: Small Molecules

FDG

Isotope(s):
Target(s):
  • Glucose Transport
Ligand Class: Small Molecules

Eligibility

Inclusion

  • Patients on adjuvant ipilimumab are allowed to participate at least 30 days from drug discontinuation as long as they have at most Grade 1 adverse events (or grade 2 if they have to received hormone replacement therapy for their otherwise grade 1 ipilimumab-induced autoimmune endocrinopathies).
  • Have histologic or cytologic biopsy-proven diagnosis of unresectable stage III or distant metastatic melanoma, irrespective of histologic type (i.e. cutaneous, unknown primary, mucosal, or ocular). Patients with resectable bulky stage IIIB or stage IIIC melanoma (for example at least 2.5-cm in shortest diameter for lymph nodes infiltrated by tumor and at least 2-cm in longest diameter for non-lymph nodes infiltrated by tumor) can also be entered into the study at the discretion of the Principal Investigator.
  • Patients who have received prior adjuvant high dose interferon are allowed to participate as long as the last injection was given at least 30 days prior to the C11-AMT PET scan and they have fully recovered from side effects (i.e., Grade ≤1 or permanent side effects that require hormone replacement therapy).
  • Have measurable disease based on RECIST v1.1. for solid tumors
  • Demonstrate adequate organ function as defined in below; all screening labs to be obtained within 14 days prior to C11-AMT PET scan: Hematological: Hemoglobin (Hgb) - ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of Hgb) Absolute Neutrophil Count (ANC) - ≥ 1,500/mm3 Platelets - ≥ 100,000/mm3 Renal: Serum Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) - ≤1.5 x ULN OR ≥ 60 mL/min using the Cockcroft-Gault formula for subject with creatinine levels \> 1.5 X institutional upper limits of normal (ULN) Hepatic: Serum Total Bilirubin - ≤ 1.5 X ULN Aspartate aminotransferase (AST) - ≤ 2.5 X ULN OR \< 5 X ULN for subjects with liver metastases Alanine aminotransferase (ALT) - ≤ 2.5 X ULN OR \< 5 X ULN for subjects with liver metastases Albumin - ≥ 2.5 mg/dL Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) - ≤1.5 X ULN, unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT) - ≤1.5 X ULN, unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

Exclusion

  • Prior history of prostate provided patient not under active systemic treatment other than hormonal therapy and with documented undetectable prostate-specific antigen (PSA) (\<0.2ng/mL),
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). 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 known active parenchymal central nervous system (CNS) metastases that are symptomatic, and/or more than one lesions, and/or their largest diameter is \> 5-mm and/or require antiepileptic drugs or corticosteroids. Patients with carcinomatous meningitis are also excluded. Exceptions are: subjects with previously treated brain metastases provided they are stable (without evidence of progression by imaging) for at least 2 weeks prior to C11-AMT and any neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are not using ongoing steroids for at least 7 days prior to C11-AMT. Patients with active (i.e. not treated with stereotactive radiosurgery), single, asymptomatic, up to 5-mm in largest diameter brain metastases (measured either by brain MRI with IV contrast or head CT with IV contrast measured within 2 weeks prior to C11-AMT) are allowed.
  • Papillary thyroid cancer. Since this malignancy very infrequently metastasizes distantly, patients with concurrent metastatic melanoma can be enrolled even if patients may: A) have just completed thyroidectomy within the last 2 years, B) have not received adjuvant radioactive iodine therapy, C) were only recently diagnosed with asymptomatic papillary thyroid cancer and their surgery is pending.
  • Lymphoma or any type or hairy-cell leukemia provided patient is not on active systemic treatment and is in complete remission, as evidenced by PET/CT scans and bone marrow biopsies for at least 3 months,
  • Prior radiation therapy for metastatic melanoma is allowed as long as the patient bears measurable actively growing disease outside the previously irradiated field. Note: If subject received major surgery, they must have recovered adequately from the toxicity (i.e., all symptoms ≤ grade 1) and/or complications from the intervention prior to starting therapy.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Hypersensitivity to pembrolizumab or any of its excipients described
  • Has received prior treatment with PD-1/PD-L1 pathway inhibitors in the adjuvant setting.
  • Adjuvant anticancer treatments are allowed at least 30 days has elapsed between the infusion/injection and C11-AMT PET scan as part of this study.
  • Non-melanoma skin cancers, non-invasive bladder cancer, and carcinoma in situ of the cervix,
  • Has had prior monoclonal antibody (mAb) targeting immune checkpoint proteins, for distant metastatic melanoma and have progressed or have developed intolerable side effect.