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

NCT03089606 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: LCCC 1531
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Association of Baseline C11-AMT PET SUV Max Value With Objective Response

  Association between intensity of C11-AMT PET at baseline, as measured by maximum standardized uptake value (SUV max) and objective response (OR) using computerized tomography images with intravenous contrast, as defined via RECIST v.1.1, at 12 weeks. Subject is considered responder if subject has CR or PR while subject is considered not-responder if they do not have CR or PR at 12 weeks. RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  12 weeks

Secondary Outcomes (5)

• Objective Response Rate

  12 Weeks

• Progression-Free Survival

  3 years

• Association of Baseline FDG-PET and C11-AMT PET

  Baseline

• Metabolic Changes

  12 weeks

• Baseline Positron Emission Tomography (PET) Parameters (SUVmax) Corresponding to Tumors That Were Subsequently Collected for Immunohistochemical (IHC) Analysis. Melanoma-specific Indoleamine 2,3-dioxygenase (IDO) Protein Expression in Research Biopsies

  Baseline

Study Arms (1)

Single Arm

OTHER

This is a single arm study. All participants completed the study interventions which are pembrolizumab treatment, FDG PET, C11-AMT PET and CT scans.

Diagnostic Test: FDG PET/CT scan; Diagnostic Test: C11-AMT PET scan; Drug: Pembrolizumab; Diagnostic Test: CT scan

Interventions

FDG PET/CT scan DIAGNOSTIC_TEST

18F-fluorodeoxy glucose (FDG) positron emission tomography (PET) with intravenous (IV) contrast images are obtained before and at the end study treatment (pembrolizumab infusion).

Single Arm

C11-AMT PET scan DIAGNOSTIC_TEST

11C-methyl-L-tryptophan (C11-AMT) positron emission tomography (PET) images are obtained before study treatment (pembrolizumab infusion).

Single Arm

Pembrolizumab DRUG

200 mg Pembrolizumab IV administered over 30 minutes on day 1. Repeat every 3 weeks for 4 cycles, until progression, or subject withdrawal for other reasons

Also known as: Keytruda

Single Arm

CT scan DIAGNOSTIC_TEST

Computerized tomography (CT) images are taken without IV contrast before the treatment (pembrolizumab infusion) and with IV contrast 3 months after the treatment start.

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign written informed consent and HIPAA authorization for release of personal health information. Note: HIPAA authorization may be included in the informed consent or obtained separately.
• Subject must be 18 years of age or more on the day of signing informed consent.
• 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.
• Have measurable disease based on RECIST v1.1. for solid tumors
• Be willing to undergo fresh tumor tissue biopsy of an accessible tumor lesion prior to pembrolizumab. A mandatory fresh biopsy will be collected following C11-AMT PET imaging. Subjects for whom fresh samples cannot be provided (e.g. inaccessible or subject safety concern) or do not agree to this fresh tumor research biopsy of accessible tumor will be deemed ineligible for study participation. Exception to the mandatory tumor tissue collection are patients with metastatic lung lesions as the only site of metastatic disease. Fresh biopsy collection from these subjects will be optional, due to high risk of pneumothorax.
• Be willing to allow for investigators to collect archival tumor tissues from surgical procedures that may have been performed before or after enrollment into this trial for research purposes (in-house cases and/or outside cases). These samples will be obtained by study staff as long as subject continues on follow-up. Blocks of tissue will be requested, and if blocks are not able to be obtained, 5micron slides (10-15) will be sufficient.
• Be willing to be injected with 11C-methyl-L-tryptophan (C11-AMT)
• Have a performance status of 0 - 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• 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

You may not qualify if:

• Is currently participating and receiving study therapy for his/her advanced melanoma or has participated in a study of an investigational agent and received study therapy in the advanced melanoma setting.
• Has received prior treatment with PD-1/PD-L1 pathway inhibitors in the adjuvant setting.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to C11-AMT PET Scan
• Has a known history of active tuberculosis (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients described
• Has had prior monoclonal antibody (mAb) targeting immune checkpoint proteins, for distant metastatic melanoma and have progressed or have developed intolerable side effect.
• 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.
• 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.
• History of prior malignancy, with the exception of the following:
• Non-melanoma skin cancers, non-invasive bladder cancer, and carcinoma in situ of the cervix,
• 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),
• Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) provided patient has isolated lymphocytosis (Rai stage 0), and does not require systemic treatment \[for "B" symptoms, Richter's transformation, lymphocyte doubling time (\<6 months), lymphadenopathy or hepatosplenomegaly\],
• 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,
• 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.
• History of malignancy provided patient has completed therapy and is free of disease for ≥ 2 years. If patient had other malignancy within the last 2 years from which he may have been completely cured by surgery alone, he may considered to be enrolled on condition that the risk of development of distant metastatic disease based on AJCC staging system is less than 30%.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

UNC Rex Healthcare

Raleigh, North Carolina, 27607, United States

Location

Related Publications (1)

• Oldan JD, Giglio BC, Smith E, Zhao W, Bouchard DM, Ivanovic M, Lee YZ, Collichio FA, Meyers MO, Wallack DE, Abernethy-Leinwand A, Long PK, Trembath DG, Googe PB, Kowalski MH, Ivanova A, Ezzell JA, Nikolaishvili-Feinberg N, Thomas NE, Wong TZ, Ollila DW, Li Z, Moschos SJ. Increased tryptophan, but not increased glucose metabolism, predict resistance of pembrolizumab in stage III/IV melanoma. Oncoimmunology. 2023 Apr 26;12(1):2204753. doi: 10.1080/2162402X.2023.2204753. eCollection 2023.

  PMID: 37123046 DERIVED

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; Tomography, X-Ray Computed

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography

Results Point of Contact

• Title: Melahat G. Canter MD MS ACRP-CP, Clinical Trial Analyst
• Organization: University of North Carolina Lineberger Comprehensive Cancer Center

Melahat_Canter@med.unc.edu

(919) 962-0000

Study Officials

• Stergios Moschos, MD

  Department of Medicine, Division of Hematology/Oncology, University of North Carolina at Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase 2, single-arm, open-label study.

Study Record Dates

• First Submitted: February 24, 2017
• First Posted: March 24, 2017
• Study Start: April 19, 2017
• Primary Completion: April 1, 2021
• Study Completion: July 1, 2023
• Last Updated: November 15, 2023
• Results First Posted: July 14, 2022

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)