Neoadjuvant Pembrolizumab for Unresectable Stage III and Unresectable Stage IV Melanoma

NCT02306850 | Completed Phase 2 Results

• 2 other identifiers: SLU IRB 2500751604
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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. 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).

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

Outcome Measures

Primary Outcomes (1)

• 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.

  24 weeks

Secondary Outcomes (1)

• Response

  24 weeks

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Open-label non-randomized trial. All subjects will receive active drug (pembrolizumab).

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

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.

Also known as: Keytruda, MK-3475

Pembrolizumab

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Males should agree to use an adequate method of contraception starting with the first dose of therapy through 120 days after last dose.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• St. Louis University: lead

Study Sites (1)

Saint Louis University Hospital

St Louis, Missouri, 63101, United States

Location

Related Publications (4)

• 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.

  PMID: 21858837 BACKGROUND

• Laks 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.

  PMID: 24499550 BACKGROUND

• Howard 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.

  PMID: 22648554 BACKGROUND

• Hamid 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.

  PMID: 23724846 BACKGROUND

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab

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

Limitations and Caveats

Limitations: a small number, 10 subjects, 9 of whom were male, participating in a study performed at a single institution. Caveat: there was a disproportionate number of subjects with cutaneous disease only, i. e. no visceral metastases.

Results Point of Contact

• Title: John Richart, MD
• Organization: Saint Louis University

john.richart@health.slu.edu

314-577-8854

Study Officials

• John M Richart, MD

  Saint Louis University, Dept. of Internal Medicine, Div. of Hematology and Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Dept. of Internal Medicine, Hematology and Oncology

Study Record Dates

• First Submitted: December 1, 2014
• First Posted: December 3, 2014
• Study Start: January 1, 2015
• Primary Completion: June 8, 2018
• Study Completion: June 8, 2018
• Last Updated: June 20, 2019
• Results First Posted: June 20, 2019

Record last verified: 2019-06

Locations

US (1)