Anti-PD-1 Antibody With HD IL-2 in Metastatic Melanoma

NCT03476174 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCRN-MMP-MEL16-261
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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

  12 months

Secondary Outcomes (3)

• Assess Adverse Events

  12 months

• Progression Free Survival (PFS)

  12 months

• Overall Survival (OS)

  12 months

Study Arms (1)

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

Drug: Pembrolizumab; Drug: Interleukin-2

Interventions

Pembrolizumab DRUG

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.

Also known as: Keytruda

Pembrolizumab and HD Interleukin 2

Interleukin-2 DRUG

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

Also known as: High Dose IL-2

Pembrolizumab and HD Interleukin 2

Eligibility Criteria

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

You may qualify if:

• 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.
• \< 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Ralph Hauke: lead
• Nebraska Cancer Specialists Methodist Estabrook Cancer Center: collaborator
• Prometheus Laboratories: collaborator

Study Sites (1)

Nebraska Cancer Specialists

Omaha, Nebraska, 68114, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; Interleukin-2

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

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Limitations and Caveats

This study was terminated early by the funder after a single subject accrual and no formal analysis was conducted for any study endpoint.

Results Point of Contact

• Title: Jeff Smith
• Organization: Hoosier Cancer Research Network

jsmith@hoosiercancer.org

317-634-5842

Study Officials

• Ralph Hauke, MD

  Nebraska Cancer Specialists Methodist Estabrook Cancer Center

  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: SPONSOR INVESTIGATOR
• PI Title: Chief of Hematology and Oncology

Study Record Dates

• First Submitted: March 16, 2018
• First Posted: March 23, 2018
• Study Start: May 7, 2018
• Primary Completion: October 16, 2019
• Study Completion: October 16, 2019
• Last Updated: October 2, 2024
• Results First Posted: October 2, 2024

Record last verified: 2024-09

Locations

US (1)