Unresectable Malignant NeoplasmPhase 2NeoPembroMelNCT02306850
Neoadjuvant Pembrolizumab for Unresectable Stage III and Unresectable Stage IV Melanoma
A Phase 2 study testing Pembrolizumab in people with Unresectable Malignant Neoplasm and Melanoma, run by St. Louis University at 1 site in United States.
Trial summary
This study is being done to see if using the study drug, pembrolizumab, can shrink down melanoma tumors enough so that they will be small enough to cut out, so that there will be no cancer left in the body. Eligible participants include those who have not received any systemic melanoma therapies (i.e. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Unresectable Malignant Neoplasm, Melanoma, Metastatic 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
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to 8 Jun 2018
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be able to provide written informed consent.
- Be 18 years old at time of consent.
- Have measurable disease by RECIST 1.1.
- Has a diagnosis of unresectable Stage III or Stage IV melanoma with anatomic site(s) of metastasis that could be amenable to curative resection if the site(s) decreased in size by up to 50% (at the investigators' discretion).
- Have provided tissue sample of a tumor lesion.
- Have an ECOG Performance status 0 or 1.
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- Demonstrate adequate organ function according to pre-defined criteria
- Females of childbearing potential should have a negative pregnancy test within 72 hours prior to receiving the first dose.
- Females of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity during the study through 120 days after last dose. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- 10 . Males should agree to use an adequate method of contraception starting with the first dose of therapy through 120 days after last dose.
Who cannot join
- 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 treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment.
- 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 > 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 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.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell and squamous cell skin cancers, or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging 4 weeks prior to the first dose and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for 7 days prior to trial treatment.
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- Has an active autoimmune disease requiring systemic treatment within the past 3 months or a history of severe autoimmune disease or syndrome that requires steroids or immunosuppressive agents.
- Has interstitial lung disease or active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results, interfere with the subject's participation, or is not in the best interest of the subject to participate, in the opinion of the investigator.
- Has known psychiatric or substance abuse disorders that would interfere with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 treatment.
- Has a history of HIV.
- Has active Hepatitis B or Hepatitis C
- Has received a live vaccine within 30 days prior to first dose.
- Is currently being treated with ipilimumab (defined as ipilimumab < 6 weeks before first dose of treatment).
Trial locations and contacts
1 site in 1 country.
United States1 site
Saint Louis University Hospital
St Louis, Missouri, 63101
About this study
Official title: Phase 2B Single-site, Open-label, Nonrandomized Study Evaluating the Efficacy of Neoadjuvant Pembrolizumab for Unresectable Stage III and Unresectable Stage IV Melanoma
This study is being done to see if using the study drug, pembrolizumab, can shrink down melanoma tumors enough so that they will be small enough to cut out, so that there will be no cancer left in the body.
Eligible participants include those who have not received any systemic melanoma therapies (i.e. participants do not have to fail ipilimumab or BRAF inhibitor) and those who have failed all available systemic options (if the participant meets other inclusion / exclusion criteria).
Read the detailed description
This study is being done to see if using the study drug, pembrolizumab, can shrink down melanoma tumors enough so that they will be small enough to cut out, so that there will be no cancer left in the body.
Eligible participants include those who have not received any systemic melanoma therapies (i.e. participants do not have to fail ipilimumab or BRAF inhibitor) and those who have failed all available systemic options (if the participant meets other inclusion / exclusion criteria).
For most melanoma cases, surgery is the recommended treatment. Until recently surgery was not used for patients with advanced melanoma (melanoma that has spread to lymph nodes or melanoma that has spread to other organs like the lung, liver, brain) because it was thought that surgery wouldn't help patients live longer when the melanoma tumors had spread beyond the skin. Recent studies have shown that patients with advanced melanoma who have surgery as one of their treatments may live longer than patients who only have systemic therapy (IV drugs or pills) and do not have surgery at all.
Unfortunately, when patients with advanced melanoma come to the doctor, surgery is not a good choice for most patients because they have 'unresectable' melanoma. 'Unresectable' melanoma means they have melanoma tumors in the body that are too big or too close to important parts in the body (like big blood vessels) to be cut out safely. We are studying if we can use a drug to shrink tumors down to make them small enough to cut out; this is called a "neoadjuvant" approach to treating melanoma. By removing all of the cancer from body by using the combination of drug and surgery, we think this could help people live longer.
Pembrolizumab is a drug that is given in the veins and can make the immune system stronger so that it can fight cancer cells. Pembrolizumab is in the class of drugs called immunotherapy.
Immunotherapy uses parts of a person's immune system to fight the disease. Pembrolizumab is designed to restore the natural ability of the immune system to recognize and target melanoma cells to be attacked. In addition to possibly shrinking tumors, it may change your immune system so that it can fight melanoma in the future.
We are also trying to learn more about how pembrolizumab works in the body. In this study, we will look at the skin, blood, and bone marrow to see if we can see any signs to tell doctors whether pembrolizumab is working or tell us which patients it may work on.
- Conditions
- Unresectable Malignant Neoplasm, Melanoma, Metastatic Melanoma, Stage IV Melanoma, Stage III Melanoma
- Being tested
- Pembrolizumab
- Keywords
- immunotherapy, PD-1 inhibitor, programmed death 1 inhibitor, neoadjuvant, pembrolizumab, MK-3475
- 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, MK-3475
At the Treatment Initiation Visit (Baseline/Day 1), subjects will begin treatment with IV pembrolizumab 200 mg infusions every 3 weeks. As in previous pembrolizumab trials, eligible subjects will receive at least 24 weeks of therapy and may receive up to 2 years of pembrolizumab therapy depending on response to treatment.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | Open-label non-randomized trial. All subjects will receive active drug (pembrolizumab). Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resectability Rate
'Resectability rate' is defined as the proportion of subjects in the trial that were unresectable at baseline who after treatment with pembrolizumab are now eligible for curative resection with complete metastectomy. The primary endpoint "resectability rate" is merely a novel statistical approach; it has no bearing on the duration of treatment that an individual patient may receive during the trial.
Measured: 24 weeks
Secondary outcomes (1)
Response
Response to treatment
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2014 (estimated)
- Study startJan 2015
- Primary completion8 Jun 2018
- Study completion8 Jun 2018
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 (4)Papers the sponsor has linked to this study.
- Other trials for Unresectable Malignant NeoplasmStudies of the same condition, open and under way.
- 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
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Louis University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Richart, M.D., St. Louis University
- Investigators
- John M Richart, MD, Principal investigator, Saint Louis University, Dept. of Internal Medicine, Div. of Hematology and Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02306850
- Sponsor's protocol ID
- SLU IRB 25007
- Other IDs
- 51604
- Acronym
- NeoPembroMel
- Status last verified
- Jun 2019
- First submitted
- 1 Dec 2014
- Last updated
- 20 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ollila DW, Gleisner AL, Hsueh EC. Rationale for complete metastasectomy in patients with stage IV metastatic melanoma. J Surg Oncol. 2011 Sep;104(4):420-4. doi: 10.1002/jso.21961.
PubMed 21858837Laks S, Brueske KA, Hsueh EC. Neoadjuvant treatment of melanoma: case reports and review. Exp Hematol Oncol. 2013 Nov 8;2(1):30. doi: 10.1186/2162-3619-2-30.
PubMed 24499550Howard JH, Thompson JF, Mozzillo N, Nieweg OE, Hoekstra HJ, Roses DF, Sondak VK, Reintgen DS, Kashani-Sabet M, Karakousis CP, Coventry BJ, Kraybill WG, Smithers BM, Elashoff R, Stern SL, Cochran AJ, Faries MB, Morton DL. Metastasectomy for distant metastatic melanoma: analysis of data from the first Multicenter Selective Lymphadenectomy Trial (MSLT-I). Ann Surg Oncol. 2012 Aug;19(8):2547-55. doi: 10.1245/s10434-012-2398-z. Epub 2012 May 31.
PubMed 22648554Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013 Jul 11;369(2):134-44. doi: 10.1056/NEJMoa1305133. Epub 2013 Jun 2.
PubMed 23724846
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2B Single-site, Open-label, Nonrandomized Study Evaluating the Efficacy of Neoadjuvant Pembrolizumab for Unresectable Stage III and Unresectable Stage IV Melanoma
- ClinicalTrials.gov ID
- NCT02306850
- Acronym / sponsor ID
- NeoPembroMel / SLU IRB 25007
- Conditions
- Unresectable Malignant Neoplasm, Melanoma, Metastatic Melanoma, Stage IV Melanoma, Stage III Melanoma
- Keywords
- immunotherapy, PD-1 inhibitor, programmed death 1 inhibitor, neoadjuvant, pembrolizumab, MK-3475
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- St. Louis UniversityUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- 8 Jun 2018 (actual)
- Study completion
- 8 Jun 2018 (actual)
- First posted
- 3 Dec 2014 (estimated)
- Results
- Posted 20 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being done to see if using the study drug, pembrolizumab, can shrink down melanoma tumors enough so that they will be small enough to cut out, so that there will be no cancer left in the body.
Eligible participants include those who have not received any systemic melanoma therapies (i.e. participants do not have to fail ipilimumab or BRAF inhibitor) and those who have failed all available systemic options (if the participant meets other inclusion / exclusion criteria).
Detailed description
This study is being done to see if using the study drug, pembrolizumab, can shrink down melanoma tumors enough so that they will be small enough to cut out, so that there will be no cancer left in the body.
Eligible participants include those who have not received any systemic melanoma therapies (i.e. participants do not have to fail ipilimumab or BRAF inhibitor) and those who have failed all available systemic options (if the participant meets other inclusion / exclusion criteria).
For most melanoma cases, surgery is the recommended treatment. Until recently surgery was not used for patients with advanced melanoma (melanoma that has spread to lymph nodes or melanoma that has spread to other organs like the lung, liver, brain) because it was thought that surgery wouldn't help patients live longer when the melanoma tumors had spread beyond the skin. Recent studies have shown that patients with advanced melanoma who have surgery as one of their treatments may live longer than patients who only have systemic therapy (IV drugs or pills) and do not have surgery at all.
Unfortunately, when patients with advanced melanoma come to the doctor, surgery is not a good choice for most patients because they have 'unresectable' melanoma. 'Unresectable' melanoma means they have melanoma tumors in the body that are too big or too close to important parts in the body (like big blood vessels) to be cut out safely. We are studying if we can use a drug to shrink tumors down to make them small enough to cut out; this is called a "neoadjuvant" approach to treating melanoma. By removing all of the cancer from body by using the combination of drug and surgery, we think this could help people live longer.
Pembrolizumab is a drug that is given in the veins and can make the immune system stronger so that it can fight cancer cells. Pembrolizumab is in the class of drugs called immunotherapy.
Immunotherapy uses parts of a person's immune system to fight the disease. Pembrolizumab is designed to restore the natural ability of the immune system to recognize and target melanoma cells to be attacked. In addition to possibly shrinking tumors, it may change your immune system so that it can fight melanoma in the future.
We are also trying to learn more about how pembrolizumab works in the body. In this study, we will look at the skin, blood, and bone marrow to see if we can see any signs to tell doctors whether pembrolizumab is working or tell us which patients it may work on.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Drug: PembrolizumabOpen-label non-randomized trial. All subjects will receive active drug (pembrolizumab). |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Be able to provide written informed consent.
- Be 18 years old at time of consent.
- Have measurable disease by RECIST 1.1.
- Has a diagnosis of unresectable Stage III or Stage IV melanoma with anatomic site(s) of metastasis that could be amenable to curative resection if the site(s) decreased in size by up to 50% (at the investigators' discretion).
- Have provided tissue sample of a tumor lesion.
Key exclusion criteria (17 listed)
- 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 treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment.
- 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 > 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 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.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell and squamous cell skin cancers, or in situ cervical cancer.
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: Keytruda, MK-3475At the Treatment Initiation Visit (Baseline/Day 1), subjects will begin treatment with IV pembrolizumab 200 mg infusions every 3 weeks. As in previous pembrolizumab trials, eligible subjects will receive at least 24 weeks of therapy and may receive up to 2 years of pembrolizumab therapy depending on response to treatment. | Drug | Pembrolizumab |
Primary outcome
Resectability Rate
Time frame: 24 weeks
'Resectability rate' is defined as the proportion of subjects in the trial that were unresectable at baseline who after treatment with pembrolizumab are now eligible for curative resection with complete metastectomy. The primary endpoint "resectability rate" is merely a novel statistical approach; it has no bearing on the duration of treatment that an individual patient may receive during the trial.
1 secondary outcome
Response
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21858837Ollila DW, Gleisner AL, Hsueh EC. Rationale for complete metastasectomy in patients with stage IV metastatic melanoma. J Surg Oncol. 2011 Sep;104(4):420-4. doi: 10.1002/jso.21961.
- Background: PubMed 24499550Laks S, Brueske KA, Hsueh EC. Neoadjuvant treatment of melanoma: case reports and review. Exp Hematol Oncol. 2013 Nov 8;2(1):30. doi: 10.1186/2162-3619-2-30.
- Background: PubMed 22648554Howard JH, Thompson JF, Mozzillo N, Nieweg OE, Hoekstra HJ, Roses DF, Sondak VK, Reintgen DS, Kashani-Sabet M, Karakousis CP, Coventry BJ, Kraybill WG, Smithers BM, Elashoff R, Stern SL, Cochran AJ, Faries MB, Morton DL. Metastasectomy for distant metastatic melanoma: analysis of data from the first Multicenter Selective Lymphadenectomy Trial (MSLT-I). Ann Surg Oncol. 2012 Aug;19(8):2547-55. doi: 10.1245/s10434-012-2398-z. Epub 2012 May 31.
- Background: PubMed 23724846Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013 Jul 11;369(2):134-44. doi: 10.1056/NEJMoa1305133. Epub 2013 Jun 2.
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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.
John M Richart, MD principal investigator
Saint Louis University, Dept. of Internal Medicine, Div. of Hematology and Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Unresectable Malignant Neoplasm and Melanoma, run by St. Louis University 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 10 inclusion and 17 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 20 Jun 2019. 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 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 20 Jun 2019). 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?
Resectability Rate (time frame: 24 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 NCT02306850, which also lists 4 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 20 Jun 2019.