MelanomaPhase 2NCT03089606
Pembrolizumab TX-naive Distant Mets Melanoma and Use of (C11-AMT) PET at Baseline as Imaging Biomarker
A Phase 2 study testing FDG PET/CT scan, C11-AMT PET scan and Pembrolizumab in people with Melanoma, run by UNC Lineberger Comprehensive Cancer Center at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- FDG PET/CT scan, C11-AMT PET scan and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 2 sitesUnited States
- Study dates
- 19 Apr 2017to 1 Jul 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Has not received prior therapy with cytotoxic T lymphocyte antigen (CTLA)-4, PD-1/PD-L1 inhibitors, other co-stimulatory or co-inhibitory immune checkpoint antibody therapies (e.g. LAG3, TIM3, cluster of differentiation (CD) 137, Killer immunoglobulin-like receptor (KIR3DL), cluster of differentiation (CD) 70, and CD27) for distant metastatic melanoma. Patients who have received mitogen-activated protein kinase (MAPK) inhibitors are allowed on condition that they have recovered from adverse events to at most Grade 1 by CTCAE v4.03 and at least 15 days have elapsed between last dose of MAPK inhibitors and C11-AMT imaging. Patients who have previously received CTLA-4 inhibitors in the adjuvant setting are allowed to participate as long as they discontinued CTLA-4 treatment at least 30 days ago and meet criteria outlined in inclusion #14. Patients who have previously received adjuvant PD-1 inhibitors are excluded.
- 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
- Female subjects of childbearing potential should have a negative urine or serum pregnancy within 14 days prior to C11-AMT PET scan. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential must be willing to use adequate methods of contraception as outlined - Contraception for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Male subjects should agree to use an adequate method of contraception as outlined - Contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- 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).
- 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).
Who cannot join
- 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.
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- 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%.
- 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.
- 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 history of (non-infectious) pneumonitis that required steroids, or any evidence of current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C virus (HCV) (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 14 days of C11-AMT PET scan. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
UNC Rex Healthcare
Raleigh, North Carolina, 27607
About this study
Official title: Pembrolizumab in Systemic Treatment-Naïve Distant Metastatic Melanoma and Exploration of Use of Baseline 11C-methyl-L-tryptophan (C11-AMT) PET Imaging as a Predictive Imaging Biomarker of Antitumor Response
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.
Read the detailed description
Objectives:
Primary Objective
Explore the association between intensity of C11-AMT 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 Response evaluation criteria in solid tumors (RECIST) 1.1 to pembrolizumab in patients with Programmed Death (PD)-1 inhibitor-naïve unresectable, American Joint Committee on Cancer (AJCC) stage III or distant metastatic (stage IV) melanoma.
Secondary Objectives
Estimate ORR (CR + PR) by RECIST 1.1 at 12 weeks to pembrolizumab in patients with PD-1 inhibitor-naïve unresectable stage III or distant metastatic metastatic melanoma (AJCC stage III/IV).
Estimate progression-free survival (PFS) in patients with unresectable stage III or distant metastatic melanoma treated with pembrolizumab as front-line therapy.
Explore associations in SUVmax and other PET parameters (e.g. total tumor metabolic volume, measurement of intra-tumoral and inter-lesional heterogeneity) between C11-AMT PET and fluorodeoxyglucose (FDG)-PET at baseline.
Explore associations between SUVmax, and other PET parameters (e.g. total tumor metabolic volume, measurement of intra-tumoral and inter-lesional heterogeneity) identified at baseline C11-AMT PET imaging with expression of components of the Indoleamine-pyrrole 2,3-dioxygenase (IDO) pathway detected by immunohistochemistry (IHC) or immunofluorescence (L -type amino acid transporter 1 (LAT1), IDO, tryptophan hydroxylase (TPH1)) and lymphocyte subtypes (CD4, cluster of differentiation 8 (CD8), FoxP3, MDSC), PD-1/PD-L1, and other immune checkpoint pathways (lymphocyte-associated gene 3 (LAG3), glucocorticoid-induced tumor necrosis factor receptor (GITR), T-cell immunoglobulin and mucin domain-3 (TIM3)) in freshly acquired tumor specimens prior to treatment with pembrolizumab.
Assess metabolic changes at week 12 (or earlier, if patient progresses) following treatment with pembrolizumab using baseline and week 12 FDG PET.
Outline:
Screening:
Physical exam, medical history, and laboratory tests, as per standard of care. Brain Magnetic resonance imaging (MRI) and Whole body FDG PET/ Computed tomography (CT) scan with IV contrast will be performed at least 24 hours before C11-AMT PET scanning. Although, the FDG PET/CT scan with IV contrast is preferred the following baseline measurements may be used if they have occurred within the below specified windows:
- Whole body FDG PET/CT scan without IV contrast, will be accepted for study purposes (i.e. correlation between baseline FDG PET scan and baseline C11-AMT scan) if it has occurred within 28 days before the C11-AMT PET scan. In this case, the patient will only be required to have a baseline CT scan of the chest, abdomen, and pelvis (also neck, if applicable) with IV contrast within 28 days of starting pembrolizumab.
- CT scan with intravenous (IV) contrast will be accepted for study purposes (i.e. baseline tumor assessment) if it has occurred within 28 days of starting pembrolizumab. In this case, the patient will only be required to have a baseline PET scan without CT coregistration 28 days prior to C11-AMT. This is to correlate baseline FDG PET with baseline C11-AMT PET parameters.
If eligibility criteria are met, patients will proceed to Study Related Scans and Biopsy:
C11-AMT PET will be performed at least 24 hours before pembrolizumab treatment and at least 24 hours after FDG PET/CT scan. A research biopsy will be performed before pembrolizumab treatment.
After screening and study related scans and biopsy, treatment will consist of the following:
Pembrolizumab 200mg IV flat dose will be administered over 30 minutes on Day 1; Pembrolizumab dosing will be repeated every 3 weeks until progression or subject withdrawal for other reasons.
At the end of treatment:
Whole body FDG PET/CT scan with IV contrast.
Projected Accrual:
Up to 25 subjects who have not received prior therapy for their recent diagnosis of distant metastatic melanoma.
- Conditions
- Melanoma
- Being tested
- FDG PET/CT scan, C11-AMT PET scan, Pembrolizumab, CT scan
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FDG PET/CT scanDiagnostic 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).
C11-AMT PET scanDiagnostic test
11C-methyl-L-tryptophan (C11-AMT) positron emission tomography (PET) images are obtained before study treatment (pembrolizumab infusion).
PembrolizumabDrug
Also called Keytruda
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
CT scanDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: FDG PET/CT scan; Diagnostic Test: C11-AMT PET scan; Drug: Pembrolizumab; Diagnostic Test: CT scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (5)
Objective Response Rate
Objective Response Rate (ORR) is defined as the number of the subjects with a Complete Response, Partial Response, stable disease, and progressive disease according to Response Evaluation Criteria in Solid Tumors ( RECIST 1.1) at 12 weeks after starting to study treatment.
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.
Measured: 12 Weeks
Progression-Free Survival
Progression Free Sruvival (PFS) is defined time from first day of treatment until disease progression as defined by RECIST1.1.
Measured: 3 years
Association of Baseline FDG-PET and C11-AMT PET
Associations of SUVmax values between baseline FDG-PET and baseline C11-AMT PET images were examined.
To objectively determine tumor regions of interest on C11-AMT and 18F FDG PET, the voxel with the highest tracer concentration (e.g., SUVmax) was determined. The voxel with the highest AMT tracer concentration (e.g., SUVmax) as well as a background region in close proximity to the location of the tumor using the MIM vista PET viewing software (MIM software Inc., Cleveland, OH, version 7.0.5).
Measured: Baseline
Metabolic Changes
Assess metabolic changes at week 12 (or earlier, if patient progresses) following treatment with pembrolizumab using baseline and week 12 FDG PET. Each lesion is considered independently since subjects might have some lesion with SUV max value increased and another lesion with SUV max value decreased.
Measured: 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
Outcome Measure Description: Associations between baseline C-methyl-L-tryptophan (C11-AMT) PET imaging and fluorodeoxyglucose (FDG) PET SUVmax values with melanoma-specific IDO expression by single colon immunohistochemistry (IHC) within the harvested tumors.
We used the following single-color IHC scoring system to semiquantify the staining intensity and percentage of positive melanoma cells: 0 (no staining), 1+ (<25% of melanoma cells with membrane or cytoplasmic stain), 2+ (25-80% of melanoma cells with the membrane of cytoplasmic stain), 3+ (>80% of melanoma cells with membrane or cytoplasmic stain) scale was used.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2017
- Study start19 Apr 2017
- Primary completion1 Apr 2021
- Study completion1 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a phase 2, single-arm, open-label study.
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Stergios Moschos, MD, Principal investigator, Department of Medicine, Division of Hematology/Oncology, University of North Carolina at Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03089606
- Sponsor's protocol ID
- LCCC 1531
- Status last verified
- Nov 2023
- First submitted
- 24 Feb 2017
- Last updated
- 15 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37123046
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pembrolizumab in Systemic Treatment-Naïve Distant Metastatic Melanoma and Exploration of Use of Baseline 11C-methyl-L-tryptophan (C11-AMT) PET Imaging as a Predictive Imaging Biomarker of Antitumor Response
- ClinicalTrials.gov ID
- NCT03089606
- Acronym / sponsor ID
- LCCC 1531
- Conditions
- Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 19 Apr 2017 (actual)
- Primary completion
- 1 Apr 2021 (actual)
- Study completion
- 1 Jul 2023 (actual)
- First posted
- 24 Mar 2017 (actual)
- Results
- Posted 14 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Objectives:
Primary Objective
Explore the association between intensity of C11-AMT 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 Response evaluation criteria in solid tumors (RECIST) 1.1 to pembrolizumab in patients with Programmed Death (PD)-1 inhibitor-naïve unresectable, American Joint Committee on Cancer (AJCC) stage III or distant metastatic (stage IV) melanoma.
Secondary Objectives
Estimate ORR (CR + PR) by RECIST 1.1 at 12 weeks to pembrolizumab in patients with PD-1 inhibitor-naïve unresectable stage III or distant metastatic metastatic melanoma (AJCC stage III/IV).
Estimate progression-free survival (PFS) in patients with unresectable stage III or distant metastatic melanoma treated with pembrolizumab as front-line therapy.
Explore associations in SUVmax and other PET parameters (e.g. total tumor metabolic volume, measurement of intra-tumoral and inter-lesional heterogeneity) between C11-AMT PET and fluorodeoxyglucose (FDG)-PET at baseline.
Explore associations between SUVmax, and other PET parameters (e.g. total tumor metabolic volume, measurement of intra-tumoral and inter-lesional heterogeneity) identified at baseline C11-AMT PET imaging with expression of components of the Indoleamine-pyrrole 2,3-dioxygenase (IDO) pathway detected by immunohistochemistry (IHC) or immunofluorescence (L -type amino acid transporter 1 (LAT1), IDO, tryptophan hydroxylase (TPH1)) and lymphocyte subtypes (CD4, cluster of differentiation 8 (CD8), FoxP3, MDSC), PD-1/PD-L1, and other immune checkpoint pathways (lymphocyte-associated gene 3 (LAG3), glucocorticoid-induced tumor necrosis factor receptor (GITR), T-cell immunoglobulin and mucin domain-3 (TIM3)) in freshly acquired tumor specimens prior to treatment with pembrolizumab.
Assess metabolic changes at week 12 (or earlier, if patient progresses) following treatment with pembrolizumab using baseline and week 12 FDG PET.
Outline:
Screening:
Physical exam, medical history, and laboratory tests, as per standard of care. Brain Magnetic resonance imaging (MRI) and Whole body FDG PET/ Computed tomography (CT) scan with IV contrast will be performed at least 24 hours before C11-AMT PET scanning. Although, the FDG PET/CT scan with IV contrast is preferred the following baseline measurements may be used if they have occurred within the below specified windows:
- Whole body FDG PET/CT scan without IV contrast, will be accepted for study purposes (i.e. correlation between baseline FDG PET scan and baseline C11-AMT scan) if it has occurred within 28 days before the C11-AMT PET scan. In this case, the patient will only be required to have a baseline CT scan of the chest, abdomen, and pelvis (also neck, if applicable) with IV contrast within 28 days of starting pembrolizumab.
- CT scan with intravenous (IV) contrast will be accepted for study purposes (i.e. baseline tumor assessment) if it has occurred within 28 days of starting pembrolizumab. In this case, the patient will only be required to have a baseline PET scan without CT coregistration 28 days prior to C11-AMT. This is to correlate baseline FDG PET with baseline C11-AMT PET parameters.
If eligibility criteria are met, patients will proceed to Study Related Scans and Biopsy:
C11-AMT PET will be performed at least 24 hours before pembrolizumab treatment and at least 24 hours after FDG PET/CT scan. A research biopsy will be performed before pembrolizumab treatment.
After screening and study related scans and biopsy, treatment will consist of the following:
Pembrolizumab 200mg IV flat dose will be administered over 30 minutes on Day 1; Pembrolizumab dosing will be repeated every 3 weeks until progression or subject withdrawal for other reasons.
At the end of treatment:
Whole body FDG PET/CT scan with IV contrast.
Projected Accrual:
Up to 25 subjects who have not received prior therapy for their recent diagnosis of distant metastatic melanoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a phase 2, single-arm, open-label study.
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Other | Diagnostic Test: FDG PET/CT scan, Diagnostic Test: C11-AMT PET scan, Drug: Pembrolizumab, Diagnostic Test: CT scanThis is a single arm study. All participants completed the study interventions which are pembrolizumab treatment, FDG PET, C11-AMT PET and CT scans. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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.
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FDG PET/CT scan18F-fluorodeoxy glucose (FDG) positron emission tomography (PET) with intravenous (IV) contrast images are obtained before and at the end study treatment (pembrolizumab infusion). | Diagnostic test | Single Arm |
| C11-AMT PET scan11C-methyl-L-tryptophan (C11-AMT) positron emission tomography (PET) images are obtained before study treatment (pembrolizumab infusion). | Diagnostic test | Single Arm |
| PembrolizumabAlso: Keytruda200 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 | Drug | Single Arm |
| CT scanComputerized tomography (CT) images are taken without IV contrast before the treatment (pembrolizumab infusion) and with IV contrast 3 months after the treatment start. | Diagnostic test | Single Arm |
Primary outcome
Association of Baseline C11-AMT PET SUV Max Value With Objective Response
Time frame: 12 weeks
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.
5 secondary outcomes
Objective Response Rate
Time frame: 12 Weeks
Progression-Free Survival
Time frame: 3 years
Association of Baseline FDG-PET and C11-AMT PET
Time frame: Baseline
Metabolic Changes
Time frame: 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
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37123046Oldan 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.
- University of North Carolina Lineberger Comprehensive Cancer Center Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stergios Moschos, MD principal investigator
Department of Medicine, Division of Hematology/Oncology, University of North Carolina at Chapel Hill
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FDG PET/CT scan, C11-AMT PET scan and Pembrolizumab in people with Melanoma, run by UNC Lineberger Comprehensive Cancer Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Association of Baseline C11-AMT PET SUV Max Value With Objective Response (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03089606, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2023.