MelanomaPhase 2NCT03476174
Anti-PD-1 Antibody With HD IL-2 in Metastatic Melanoma
A Phase 2 study testing Pembrolizumab and Interleukin-2 in people with Melanoma, run by Ralph Hauke at 1 site in United States.
Trial summary
The primary objective of this single arm phase 2 trial is to assess the response rate [complete response (CR) + partial response (PR)] of sequential therapy of pembrolizumab followed by HD IL-2 in subjects with stage IV malignant 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 Interleukin-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 7 May 2018to 16 Oct 2019
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- ECOG Performance Status of 0-1 within 28 days prior to registration (Appendix 1).
- Life expectancy of 6 months or greater as determined by the site investigator.
- Histologically-confirmed diagnosis of unresectable stage IV or metastatic melanoma not amenable to local therapy.
- Measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1 (Section 9), and obtained by imaging within 28 days prior to registration for protocol therapy.
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- < 2 lines of prior therapy for metastatic melanoma. Cannot have received prior therapy with HD IL-2. May have had one prior line of therapy that included a check point inhibitor.
- Prior systemic cancer treatment must be completed at least 21 days prior to first dose of study drug and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia or vitiligo) to Grade ≤ 1 or baseline.
- Not received radiation therapy within 21 days of initiation of study treatment, and the measurable disease must have been outside of the radiation port.
- Demonstrate adequate organ function. All screening labs to be obtained within 28 days prior to registration.
- WBC ≥ 3,000/L
- ANC ≥ 1,000/L
- Hgb ≥ 9g/dL
- Plt ≥ 100 × 10(9)/L
- Serum creatinine ≤ 1.5 mg/dL
- Calculated creatinine clearance ≥ 40 mL/min; if serum creatinine > 1.5 mg/dL
- Total Bilirubin ≤ 1.5 × upper limit of normal (ULN)
- Direct Bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT)≤ 2.5 × ULN or ≤ 5 x ULN for subjects with known hepatic metastasis
- International Normalized Ratio (INR) ≤ 1.5 × ULN; For subjects receiving warfarin or LMWH, the subjects must, in the site investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.5 × ULN if that is the goal of anticoagulant therapy.
- Adequate baseline pulmonary function test (PFT) (FEV1 > 2 L or ≥ 75% of predicted for height and age).
- Documented left ventricular ejection fraction (LVEF) of > 45%, testing is required in patients with:
- Age ≥ 60 years old
- Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
- History of coronary revascularization or ischemic symptoms
- Archival tissue (from the primary tumor or metastases) is mandatory if available for correlative studies. If archived tumor tissue is not available, the patient does not need to undergo a biopsy to obtain tissue and is still eligible for study.
- Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
- Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 120 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
- Male subjects who are not surgically sterile (vasectomy) must agree to use an adequate method of contraception. Male subjects with female sexual partners who are pregnant, possibly pregnant or who could become pregnant during the study must agree to use condoms from the first dose of study drug through 120 days after the last dose of study therapy. Total abstinence for the same study period is an acceptable alternative.
- As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Who cannot join
- Active infection requiring systemic therapy
- Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study.
- Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
- Active central nervous system (CNS) metastases. NOTE: if prior metastasis but treated and clinically stable for 1 month after treatment are eligible. Subjects with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible.
- Surgery within 4 weeks prior to study treatment except for minor procedures. NOTE: Hepatic biliary stent placement is allowed.
- Uncontrolled or poorly-controlled hypertension (> 160 mmHg systolic or > 100 mmHg diastolic for > 4 weeks) despite standard medical management.
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- Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to initiation of study treatment.
- Any Grade 3-4 GI bleeding within 3 months prior to initiation of study treatment.
- History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to initiation of study treatment.
- Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to initiation of study treatment.
- Gross hemoptysis within 2 months of initiation of study treatment.
- Has any condition that, in the opinion of the investigator, might jeopardize the safety of the patient or interfere with protocol compliance.
- Has any mental or medical condition that prevents the patient from giving informed consent or participating in the trial.
- Known hypersensitivity to pembrolizumab or IL-2 or any of their components.
- Known history of active tuberculosis.
- Concurrent systemic steroid therapy with doses above physiologic level.
- History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
- Subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
- Subjects with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
- Subjects with a history of celiac disease may be eligible if controlled with diet.
- Treatment with any investigational agent within 21 days prior to initiation of study treatment and the subject must have recovered from the acute toxic effects of the regimen.
- Prior organ transplant including allogeneic transplantation.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: MMP-01: Pilot Study Evaluating Activity of the Combination of Anti-PD-1 Antibody With High Dose IL-2 in Metastatic Melanoma
The primary objective of this single arm phase 2 trial is to assess the response rate [complete response (CR) + partial response (PR)] of sequential therapy of pembrolizumab followed by HD IL-2 in subjects with stage IV malignant melanoma. Response assessment will be performed after pembrolizumab therapy, and response reassessment will be performed after HD IL-2 therapy using revised RECIST 1.1.
- Conditions
- Melanoma
- Being tested
- Pembrolizumab, Interleukin-2
- 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
Subjects will receive 200 mg pembrolizumab every 3 weeks for two cycles. Cycle length is 21 days (i.e., 3 weeks). On the last day of Cycle 2 (+/- 3 days), disease status will be assessed via imaging.
Interleukin-2Drug
Also called High Dose IL-2
Following the pembrolizumab treatment, HD IL-2 treatment will commence. After completing the 2 cycles of pembrolizumab, High Dose Interleukin-2 (HD IL-2) will be administered. This will require a hospital stay of at least 5 days for each treatment cycle. Established guidelines will be followed for safely administering HD-IL-2 and managing toxicities from this treatment. Two treatment cycles will be administered, Cycle 2 being separated from Cycle 1 by approximately 9 days after completion (assuming subject has recovered from Cycle 1 adequately to proceed with Cycle 2). Four weeks after completion of the 2 cycles (called a course of HD IL-2 therapy), disease status will be monitored via CT of the chest and abdomen/pelvis using revised RECIST guidelines
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab and HD Interleukin 2 | Experimental | Pembrolizumab 200 mg IV over 30 minutes; Day 1 of each cycle 3 weeks (21 days) for 2 cycles. IL-2 600,000 IU/kg2 IV over 15 minutes every 8 hours for up to 14 doses over 5 days; Days 1-5 = Cycle 1; 9 days of rest in between; Days 15-19 = Cycle 2 Receives: Drug: Pembrolizumab; Drug: Interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
Assess the response rate [complete response (CR) + partial response (PR)] of sequential therapy of pembrolizumab followed by HD IL-2 in subjects with stage IV malignant melanoma. Response assessment will be performed using revised RECIST 1.1
Measured: 12 months
Secondary outcomes (3)
Assess Adverse Events
Assess adverse events via CTCAE v4.03
Measured: 12 months
Progression Free Survival (PFS)
Measure Progression-Free Survival (PFS) using revised RECIST guideline (version 1.1) after completion of 2 cycles of pembrolizumab and 2 cycles of HD IL-2 in all the subjects enrolled in the study. PFS is defined as the time from treatment initiation until objective tumor progression or death.
Measured: 12 months
Overall Survival (OS)
Measure overall survival (OS) at 12 months in subjects with stage IV malignant melanoma who showed a response [stable disease (SD), complete response (CR) or partial response (PR)] following completion of 2 cycles of pembrolizumab and 2 cycles of HD IL-2. OS is defined as time from treatment initiation until death from any cause
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2018
- Study start7 May 2018
- Primary completion16 Oct 2019
- Study completion16 Oct 2019
Why it stopped: Lack of Accrual
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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ralph Hauke
- Sponsor type
- University, hospital or other
- Collaborators
- Nebraska Cancer Specialists Methodist Estabrook Cancer Center, Prometheus Laboratories
- Responsible party
- Sponsor-investigator, Ralph Hauke, Hoosier Cancer Research Network
- Investigators
- Ralph Hauke, MD, Principal investigator, Nebraska Cancer Specialists Methodist Estabrook Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03476174
- Sponsor's protocol ID
- HCRN-MMP-MEL16-261
- Status last verified
- Sep 2024
- First submitted
- 16 Mar 2018
- Last updated
- 2 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MMP-01: Pilot Study Evaluating Activity of the Combination of Anti-PD-1 Antibody With High Dose IL-2 in Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT03476174
- Acronym / sponsor ID
- HCRN-MMP-MEL16-261
- Conditions
- Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of Accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Ralph HaukeUniversity, hospital or other
- Collaborators
- Nebraska Cancer Specialists Methodist Estabrook Cancer Center, Prometheus Laboratories
- Study start
- 7 May 2018 (actual)
- Primary completion
- 16 Oct 2019 (actual)
- Study completion
- 16 Oct 2019 (actual)
- First posted
- 23 Mar 2018 (actual)
- Results
- Posted 2 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this single arm phase 2 trial is to assess the response rate [complete response (CR) + partial response (PR)] of sequential therapy of pembrolizumab followed by HD IL-2 in subjects with stage IV malignant melanoma. Response assessment will be performed after pembrolizumab therapy, and response reassessment will be performed after HD IL-2 therapy using revised RECIST 1.1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab and HD Interleukin 2 | Experimental | Drug: Pembrolizumab, Drug: Interleukin-2Pembrolizumab 200 mg IV over 30 minutes; Day 1 of each cycle 3 weeks (21 days) for 2 cycles. IL-2 600,000 IU/kg2 IV over 15 minutes every 8 hours for up to 14 doses over 5 days; Days 1-5 = Cycle 1; 9 days of rest in between; Days 15-19 = Cycle 2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- ECOG Performance Status of 0-1 within 28 days prior to registration (Appendix 1).
- Life expectancy of 6 months or greater as determined by the site investigator.
- Histologically-confirmed diagnosis of unresectable stage IV or metastatic melanoma not amenable to local therapy.
Key exclusion criteria (22 listed)
- Active infection requiring systemic therapy
- Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study.
- Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
- Active central nervous system (CNS) metastases. NOTE: if prior metastasis but treated and clinically stable for 1 month after treatment are eligible. Subjects with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible.
- Surgery within 4 weeks prior to study treatment except for minor procedures. NOTE: Hepatic biliary stent placement is allowed.
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: KeytrudaSubjects will receive 200 mg pembrolizumab every 3 weeks for two cycles. Cycle length is 21 days (i.e., 3 weeks). On the last day of Cycle 2 (+/- 3 days), disease status will be assessed via imaging. | Drug | Pembrolizumab and HD Interleukin 2 |
| Interleukin-2Also: High Dose IL-2Following the pembrolizumab treatment, HD IL-2 treatment will commence. After completing the 2 cycles of pembrolizumab, High Dose Interleukin-2 (HD IL-2) will be administered. This will require a hospital stay of at least 5 days for each treatment cycle. Established guidelines will be followed for safely administering HD-IL-2 and managing toxicities from this treatment. Two treatment cycles will be administered, Cycle 2 being separated from Cycle 1 by approximately 9 days after completion (assuming subject has recovered from Cycle 1 adequately to proceed with Cycle 2). Four weeks after completion of the 2 cycles (called a course of HD IL-2 therapy), disease status will be monitored via CT of the chest and abdomen/pelvis using revised RECIST guidelines | Drug | Pembrolizumab and HD Interleukin 2 |
Primary outcome
Response Rate
Time frame: 12 months
Assess the response rate [complete response (CR) + partial response (PR)] of sequential therapy of pembrolizumab followed by HD IL-2 in subjects with stage IV malignant melanoma. Response assessment will be performed using revised RECIST 1.1
3 secondary outcomes
Assess Adverse Events
Time frame: 12 months
Progression Free Survival (PFS)
Time frame: 12 months
Overall Survival (OS)
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Ralph Hauke, MD principal investigator
Nebraska Cancer Specialists Methodist Estabrook Cancer Center
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 and Interleukin-2 in people with Melanoma, run by Ralph Hauke 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 31 inclusion and 22 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: stopped early, as of the sponsor's last update on 2 Oct 2024. 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 2 Oct 2024). 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?
Response Rate (time frame: 12 months). 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 2 Oct 2024.