Malignant MelanomaPhase 1NCT02434354
A Tissue Collection Study of Pembrolizumab (MK-3475) in Subjects With Resectable Advanced Melanoma
A Phase 1 study testing pembrolizumab in people with Malignant Melanoma, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
The main purpose of this trial is to evaluate the safety, tolerability and adverse event profile of pembrolizumab in subjects who have high risk melanoma before and after their standard of care surgical resection, and to collect tumor tissue from subjects before and after receipt of pembrolizumab to look at how the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to 29 Sep 2021
- Phase
- Phase 1
- 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
- The subject must have clinical stage III or resectable stage IV MEL. Subject's may not have a diagnosis of uveal or mucosal melanoma.
- The subject must be expected to have an adequate amount of tumor burden to yield 2-4 pre-operative research core biopsy (14-gauge needle) specimens or the equivalent amount of tissue (4-6 mm punch biopsy), in addition, to the tissue required for diagnostic purposes.
- The subject must be expected to have an adequate amount of residual tumor after their pre-operative research tumor tissue collection, such that their operative research tumor collection will also yield at least 4-6 research core biopsy specimens or the equivalent amount of tissue
- The subject must be willing to undergo the two paired tumor tissue biopsy procedures to obtain samples for biomarker analysis. Tissue obtained must not be previously irradiated.
- Either the subject or the subject's legal representative must be willing and able to provide written informed consent for the trial.
- The subject must be ≥ 18 years of age on day of signing informed consent.
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- The subject must have a performance status of 0 or 1 on the ECOG Performance Scale.
- The subject must demonstrate adequate organ function as defined in Table 1, all screening labs must be performed within 10 days of treatment initiation.
- Table 1 Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC)
- 1500/mcL Platelets
- 100,000/ mcL Hemoglobin
- 9 g/dL or ≥5.6 mmol/L Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl)
- ≤1.5 X upper limit of normal (ULN) OR
- 50 mL/min for subject with creatinine levels > 1.5 X institutional ULN UPCC# 01615: Tissue Collection Study of Pembrolizumab in Advanced Melanoma Version Date: 12/30/2014 Page 10 Hepatic Serum total bilirubin
- 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT)
- 2.5 X ULN OR
- 5 X ULN for subjects with liver metastases Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) 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
- 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 aCreatinine clearance should be calculated per institutional standard.
- Female subject's of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
- The subject must be willing to use protocol defined method(s) of contraception:
- Female subjects of childbearing potential must be willing to use 2 methods of contraception, or abstain from heterosexual sexual intercourse for two weeks before the time of the first dose of study medication, while on study, through 120 days after the last dose of study medication.
- Female subject's of childbearing potential are defined as those women who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male subjects must agree to use an adequate method of contraception starting with the first dose of study medication, while on study, through 120 days after the last dose of study medication.
- Acceptable forms of birth control include condoms, diaphragms, cervical cap, an intra-uterine device (IUD), surgical sterility (tubal ligation or a partner that has undergone a vasectomy), or oral contraceptives, OR the subject must agree to completely abstain from heterosexual intercourse. Abstinence at certain times of the cycle only, such as during the days of ovulation, after ovulation and withdrawal are not acceptable methods of birth control
Who cannot join
- Subject has unresectable disease; i.e. in the opinion of the surgical oncologist, all of the subject's melanoma cannot be completely removed with a clear margin.
- Subject is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment.
- Subject has a known hypersensitivity to pembrolizumab or any of its ingredients.
- Subject has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment.
- Subject has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Subject has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agents (including ipilimumab), interferon, high dose IL-1 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
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- Subject has had prior chemotherapy, targeted small molecule therapy, 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion
- For subject's who have received major surgery, the subject must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study therapy.
- Subject has had radiation therapy to the tumor selected for research collection, or has had radiation therapy to any site within 4 weeks prior to study Day 1.
- Subject has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to study Day 1.
- Subject has a known additional malignancy that is progressing or requires active treatment.
- Subject has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Note: Subjects with previously treated brain metastases will be eligible to participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
- Subject has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
- Note: Subjects with vitiligo or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections will not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
- Subject has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Subject has an active infection requiring systemic therapy, including active tuberculosis
- Subject 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.
- Subject has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Subject is pregnant or breastfeeding, or expecting to conceive or father a child within the projected duration of the trial participation (from 2 weeks prior to the first dose of study treatment, while participating on the study and through 120 days after the last dose of trial treatment).
- Subject has severe cardiovascular disease, i.e. arrhythmias, requiring chronic treatment, congestive heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease.
- Subject has hepatic decompensation (Child-Pugh score >6 [class B and C]).
- Subject has uncontrolled thyroid dysfunction
- Subject has uncontrolled diabetes mellitus
- Subject has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) as determined by medical record review.
- Subject has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected) as determined by medical record review.
- Subject has received a live vaccine within 30 days prior to the first dose of trial treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase Ib Tissue Collection Study of Pembrolizumab (MK-3475) in Subjects With Resectable Advanced Melanoma
The main purpose of this trial is to evaluate the safety, tolerability and adverse event profile of pembrolizumab in subjects who have high risk melanoma before and after their standard of care surgical resection, and to collect tumor tissue from subjects before and after receipt of pembrolizumab to look at how the experimental drug interacts with tumor tissue. Subjects will receive 1 dose of neoadjuvant pembrolizumab, followed by complete resection and then a year of adjuvant pembrolizumab
Read the detailed description
detailed description listed above
- Conditions
- Malignant Melanoma
- Being tested
- pembrolizumab
- Keywords
- Clinical stage III or resectable stage IV melanoma (MEL)
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pembrolizumabDrug
Also called keytruda
200 mg Subjects will receive 1 dose of neoadjuvant pembrolizumab, followed by complete resection and then a year of adjuvant pembrolizumab
| Study group | Role | What they receive |
|---|---|---|
| neo-adjuvant/adjuvant pembrolizaumab 200 mg IV | Experimental | All subjects will receive 1 cycle neo-adjuvant pembrolizumab 200mg IV followed by complete surgical resection followed by pembrolizumab Q3weeks for 1 year Receives: Drug: pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants (%) With CTCAE Graded Adverse Events
Safety as defined by 1) all grade 3/4 adverse events and 2) any grade adverse event that occurred in>5% of patients. Toxicities are graded using CTCAE Version 4.
Measured: within 30 days of final study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2015 (estimated)
- Study startApr 2015
- Primary completionJul 2019
- Study completion29 Sep 2021
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 (2)Papers the sponsor has linked to this study.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tara Mitchell, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02434354
- Sponsor's protocol ID
- UPCC 01615
- Status last verified
- May 2022
- First submitted
- 30 Apr 2015
- Last updated
- 16 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Study already published
Publications
Huang AC, Orlowski RJ, Xu X, Mick R, George SM, Yan PK, Manne S, Kraya AA, Wubbenhorst B, Dorfman L, D'Andrea K, Wenz BM, Liu S, Chilukuri L, Kozlov A, Carberry M, Giles L, Kier MW, Quagliarello F, McGettigan S, Kreider K, Annamalai L, Zhao Q, Mogg R, Xu W, Blumenschein WM, Yearley JH, Linette GP, Amaravadi RK, Schuchter LM, Herati RS, Bengsch B, Nathanson KL, Farwell MD, Karakousis GC, Wherry EJ, Mitchell TC. A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat Med. 2019 Mar;25(3):454-461. doi: 10.1038/s41591-019-0357-y. Epub 2019 Feb 25.
PubMed 30804515Sharon CE, Tortorello GN, Ma KL, Huang AC, Xu X, Giles LR, McGettigan S, Kreider K, Schuchter LM, Mathew AJ, Amaravadi RK, Gimotty PA, Miura JT, Karakousis GC, Mitchell TC. Long-term outcomes to neoadjuvant pembrolizumab based on pathological response for patients with resectable stage III/IV cutaneous melanoma. Ann Oncol. 2023 Sep;34(9):806-812. doi: 10.1016/j.annonc.2023.06.006. Epub 2023 Jul 4.
PubMed 37414215
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Tissue Collection Study of Pembrolizumab (MK-3475) in Subjects With Resectable Advanced Melanoma
- ClinicalTrials.gov ID
- NCT02434354
- Acronym / sponsor ID
- UPCC 01615
- Conditions
- Malignant Melanoma
- Keywords
- Clinical stage III or resectable stage IV melanoma (MEL)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- Apr 2015 (actual)
- Primary completion
- Jul 2019 (actual)
- Study completion
- 29 Sep 2021 (actual)
- First posted
- 5 May 2015 (estimated)
- Results
- Posted 5 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this trial is to evaluate the safety, tolerability and adverse event profile of pembrolizumab in subjects who have high risk melanoma before and after their standard of care surgical resection, and to collect tumor tissue from subjects before and after receipt of pembrolizumab to look at how the experimental drug interacts with tumor tissue. Subjects will receive 1 dose of neoadjuvant pembrolizumab, followed by complete resection and then a year of adjuvant pembrolizumab
Detailed description
detailed description listed above
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| neo-adjuvant/adjuvant pembrolizaumab 200 mg IV | Experimental | Drug: pembrolizumabAll subjects will receive 1 cycle neo-adjuvant pembrolizumab 200mg IV followed by complete surgical resection followed by pembrolizumab Q3weeks for 1 year |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- The subject must have clinical stage III or resectable stage IV MEL. Subject's may not have a diagnosis of uveal or mucosal melanoma.
- The subject must be expected to have an adequate amount of tumor burden to yield 2-4 pre-operative research core biopsy (14-gauge needle) specimens or the equivalent amount of tissue (4-6 mm punch biopsy), in addition, to the tissue required for diagnostic purposes.
- The subject must be expected to have an adequate amount of residual tumor after their pre-operative research tumor tissue collection, such that their operative research tumor collection will also yield at least 4-6 research core biopsy specimens or the equivalent amount of tissue
- The subject must be willing to undergo the two paired tumor tissue biopsy procedures to obtain samples for biomarker analysis. Tissue obtained must not be previously irradiated.
- Either the subject or the subject's legal representative must be willing and able to provide written informed consent for the trial.
Key exclusion criteria (27 listed)
- Subject has unresectable disease; i.e. in the opinion of the surgical oncologist, all of the subject's melanoma cannot be completely removed with a clear margin.
- Subject is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment.
- Subject has a known hypersensitivity to pembrolizumab or any of its ingredients.
- Subject has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment.
- Subject has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
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 |
|---|---|---|
| pembrolizumabAlso: keytruda200 mg Subjects will receive 1 dose of neoadjuvant pembrolizumab, followed by complete resection and then a year of adjuvant pembrolizumab | Drug | neo-adjuvant/adjuvant pembrolizaumab 200 mg IV |
Primary outcome
Number of Participants (%) With CTCAE Graded Adverse Events
Time frame: within 30 days of final study treatment
Safety as defined by 1) all grade 3/4 adverse events and 2) any grade adverse event that occurred in>5% of patients. Toxicities are graded using CTCAE Version 4.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30804515Huang AC, Orlowski RJ, Xu X, Mick R, George SM, Yan PK, Manne S, Kraya AA, Wubbenhorst B, Dorfman L, D'Andrea K, Wenz BM, Liu S, Chilukuri L, Kozlov A, Carberry M, Giles L, Kier MW, Quagliarello F, McGettigan S, Kreider K, Annamalai L, Zhao Q, Mogg R, Xu W, Blumenschein WM, Yearley JH, Linette GP, Amaravadi RK, Schuchter LM, Herati RS, Bengsch B, Nathanson KL, Farwell MD, Karakousis GC, Wherry EJ, Mitchell TC. A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat Med. 2019 Mar;25(3):454-461. doi: 10.1038/s41591-019-0357-y. Epub 2019 Feb 25.
- Derived from this study: PubMed 37414215Sharon CE, Tortorello GN, Ma KL, Huang AC, Xu X, Giles LR, McGettigan S, Kreider K, Schuchter LM, Mathew AJ, Amaravadi RK, Gimotty PA, Miura JT, Karakousis GC, Mitchell TC. Long-term outcomes to neoadjuvant pembrolizumab based on pathological response for patients with resectable stage III/IV cutaneous melanoma. Ann Oncol. 2023 Sep;34(9):806-812. doi: 10.1016/j.annonc.2023.06.006. Epub 2023 Jul 4.
- Pubmed linkLink provided by the sponsor.
- Individual participant dataSharing planned: No. Study already published
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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.
Tara Mitchell, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing pembrolizumab in people with Malignant Melanoma, run by Abramson Cancer Center at Penn Medicine at 1 site 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 27 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 16 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 5 Jan 2021). 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?
Number of Participants (%) With CTCAE Graded Adverse Events (time frame: within 30 days of final study treatment). 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 NCT02434354, which also lists 2 linked publications.
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 16 Jun 2022.