MelanomaPhase 1NCT02339324
Neoadjuvant Combination Biotherapy With Pembrolizumab and High Dose IFN-alfa2b
A Phase 1 study testing Pembrolizumab and high dose interferon alfa-2b (HDI) in people with Melanoma, run by Yana Najjar at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Pembrolizumab and high dose interferon alfa-2b (HDI)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Mar 2015to 2 Nov 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Able to provide written informed consent.
- At least 18 years of age.
- Melanoma belonging to the following stages:
- Tx or T1-4 and
- N1b, or N2b, or N2c, or N3 and
- M 0
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- 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.
- Have measurable disease.
- Provide tumor tissue from a newly obtained biopsy.
- ECOG performance status of 0 or 1.
- Adequate organ function.
Who cannot join
- 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.
- 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.
- 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.
- 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.
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- 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.
- Has evidence of 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 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 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.
- 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 (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days prior to the first dose of trial treatment.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
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
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.
Read the 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.
- Conditions
- Melanoma
- Being tested
- Pembrolizumab and high dose interferon alfa-2b (HDI)
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab and high dose interferon alfa-2b (HDI)Drug
Also called MK-3475 and Intron A
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.
| Study group | Role | What they receive |
|---|---|---|
| This study has one arm that consists of 3 phases or steps. | Experimental | 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 Receives: Drug: Pembrolizumab and high dose interferon alfa-2b (HDI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of participants who experience adverse events.
Measured: Up to 90 days (per patient); Up to 5 years (for cohort)
Secondary outcomes (1)
Evaluate changes in immunologic biomarkers in the blood and in the tumor tissue and assess their association with resposne to treatment.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2015 (estimated)
- Study start6 Mar 2015
- Primary completion1 Sep 2019
- Study completion2 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- PI will be leaving this institution and has elected to close this trial to accrual
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yana Najjar
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Yana Najjar, University of Pittsburgh
- Investigators
- Yana Najjar, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02339324
- Sponsor's protocol ID
- UPCI 14-102
- Status last verified
- Feb 2021
- First submitted
- 7 Dec 2014
- Last updated
- 24 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02339324
- Acronym / sponsor ID
- UPCI 14-102
- Conditions
- Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Yana NajjarUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 6 Mar 2015 (actual)
- Primary completion
- 1 Sep 2019 (actual)
- Study completion
- 2 Nov 2019 (actual)
- First posted
- 15 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- PI will be leaving this institution and has elected to close this trial to accrual
| Arm | Type | Receives |
|---|---|---|
| This study has one arm that consists of 3 phases or steps. | Experimental | Drug: Pembrolizumab and high dose interferon alfa-2b (HDI)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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Able to provide written informed consent.
- At least 18 years of age.
- Melanoma belonging to the following stages:
- 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:
- NOTE: A pt should be determined to be potentially surgically resectable at baseline to be eligible for this neoadjuvant study.
Key exclusion criteria (16 listed)
- 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.
- 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.
- 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.
- 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.
- 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.
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 |
|---|---|---|
| Pembrolizumab and high dose interferon alfa-2b (HDI)Also: MK-3475 and Intron APembrolizumab 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. | Drug | This study has one arm that consists of 3 phases or steps. |
Primary outcome
The number of participants who experience adverse events.
Time frame: Up to 90 days (per patient); Up to 5 years (for cohort)
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2021.
- 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.
Yana Najjar, MD principal investigator
University of Pittsburgh
2 sites 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 and high dose interferon alfa-2b (HDI) in people with Melanoma, run by Yana Najjar 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 17 inclusion and 16 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 24 Feb 2021. 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The number of participants who experience adverse events. (time frame: Up to 90 days (per patient); Up to 5 years (for cohort)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Feb 2021.