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Neoadjuvant Combination Biotherapy With Pembrolizumab and High Dose IFN-alfa2b

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02339324
Recruitment Status : Completed
First Posted : January 15, 2015
Last Update Posted : February 24, 2021
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Yana Najjar, University of Pittsburgh

Brief Summary:
This study plans to to estimate the safety profile of the combination biotherapy regimen consisting of standard-dose interferon alpha-2b (HDI) and anti-PD1 monoclonal antibody, Pembrolizumab, for the neoadjuvant therapy of locally/regionally advanced/recurrent melanoma. Also, the objectives of this trial include the evaluation of prognostic and predictive biomarkers, radiologic preoperative response rate, pathologic response rate, progression free survival and overall survival. Up to 30 evaluable patients will be accrued.

Condition or disease Intervention/treatment Phase
Melanoma Drug: Pembrolizumab and high dose interferon alfa-2b (HDI) Phase 1

Detailed Description:

The study has 3 main phases:

Induction Phase:

Pembrolizumab I.V. infusion every 3-4 weeks for 2 doses (starting first week of HDI administration) given concurrently with HDI I.V. x 5 consecutive days out of 7 every week for 4 weeks, followed by S.C. every other day 3 times each week for 2 weeks.

This is followed by definitive surgery (week 6-8).

Maintenance Phase (following recovery from surgery):

Pembrolizumab I.V. infusion every 3 weeks given concurrently with HDI S.C. QOD TIW every week for 46 additional weeks.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: PI will be leaving this institution and has elected to close this trial to accrual
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Combination Biotherapy With Pembrolizumab and High Dose IFN-alfa2b in Patients With Locally/Regionally Advanced/Recurrent Melanoma: Safety, Efficacy and Biomarker Study
Actual Study Start Date : March 6, 2015
Actual Primary Completion Date : September 1, 2019
Actual Study Completion Date : November 2, 2019

Arm Intervention/treatment
Experimental: This study has one arm that consists of 3 phases or steps.

Induction phase (first 6 weeks): Pembrolizumab and High Dose IFNα-2b (HDI) Pembrolizumab I.V. every 3-4 weeks for 2 doses concurrently with HDI I.V. x 5 consecutive days every week for 4 weeks, followed by S.C. every other day 3x each week for 2 weeks.

Surgery phase (week 6-8).

Maintenance phase (following recovery from surgery): Pembrolizumab I.V. infusion every 3 weeks given concurrently with HDI S.C. QOD (e.g. M,W,F) TIW every week for 46 additional weeks

Drug: Pembrolizumab and high dose interferon alfa-2b (HDI)
Pembrolizumab and HDI will be given concurrently during the induction phase of the study for up to 6 weeks from treatment initiation. This is followed by surgery. After recovery from surgery, pembrolizumab and HDI will be reinitiated as maintenance therapy during the maintenance phase of the study.
Other Name: MK-3475 and Intron A

Primary Outcome Measures :
  1. The number of participants who experience adverse events. [ Time Frame: Up to 90 days (per patient); Up to 5 years (for cohort) ]

Secondary Outcome Measures :
  1. Evaluate changes in immunologic biomarkers in the blood and in the tumor tissue and assess their association with resposne to treatment. [ Time Frame: Up to 5 years ]

Other Outcome Measures:
  1. radiologic preoperative response rate [ Time Frame: Up to 5 years ]
  2. pathologic response rate [ Time Frame: Up to 5 years ]
  3. progression free survival [ Time Frame: Up to 5 years ]
  4. overall survival [ Time Frame: Up to 5 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Able to provide written informed consent.
  2. At least 18 years of age.
  3. Melanoma belonging to the following stages:

    • Tx or T1-4 and
    • N1b, or N2b, or N2c, or N3 and
    • M 0

    Pts are eligible for this trial either at presentation for primary melanoma with concurrent regional nodal and/or in-transit metastasis, or at the time of clinically detected nodal and/or in-transit recurrence and may belong to any of the following groups:

    • Primary melanoma with clinically apparent regional lymph node metastases.
    • Clinically detected recurrence of melanoma at the proximal regional lymph node(s) basin.
    • Clinically detected primary melanoma involving multiple regional nodal groups.
    • Clinically detected single site of nodal metastatic melanoma arising from an unknown primary.
    • Pts with intransit or satelite metastases with or without lymph node involvement are allowed if they are considered potentially surgically resectable at baseline.

    NOTE: A pt should be determined to be potentially surgically resectable at baseline to be eligible for this neoadjuvant study.

  4. Have measurable disease.
  5. Provide tumor tissue from a newly obtained biopsy.
  6. ECOG performance status of 0 or 1.
  7. Adequate organ function.

Exclusion Criteria:

  1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 wks of the first dose of treatment.
  2. 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 trial treatment.
  3. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 wks 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 and may qualify for the study.
    • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  4. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
  5. Has an active automimmune 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. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
  6. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  7. Has an active infection requiring systemic therapy.
  8. 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.
  9. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  10. 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.
  11. 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) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Prior treatment with interferon alfa is allowed. Patients with history of allergic or hypersensitivity reaction to interferon alfa are excluded.
  12. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  13. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  14. Has received a live vaccine within 30 days prior to the first dose of trial treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02339324

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United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, Pennsylvania
Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Yana Najjar
Merck Sharp & Dohme Corp.
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Principal Investigator: Yana Najjar, MD University of Pittsburgh
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Responsible Party: Yana Najjar, Principal Investigator, University of Pittsburgh Identifier: NCT02339324    
Other Study ID Numbers: UPCI 14-102
First Posted: January 15, 2015    Key Record Dates
Last Update Posted: February 24, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Interferon alpha-2
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs