High Dose IL-2 in Combination With Anti-PD-1 in Metastatic Melanoma and Renal Cell Carcinoma

Renal Cell Carcinoma Clinical Trial

Official title:

High Dose IL-2 in Combination With Anti-PD-1 to Overcome Anti-PD-1 Resistance in Metastatic Melanoma and Renal Cell Carcinoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03889782
• Other study ID #: 181398
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: October 2019
• Est. completion date: October 2022

Study information

• Verified date: March 2019
• Source: University of California, San Diego
• Contact: Mina Nikanjam, MD PhD
• Phone: 858-246-2706
• Email: mnikanjam[@]ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to study the effectiveness of the combination of drugs called nivolumab and high dose interleukin-2 (HD IL-2) as a treatment for metastatic (the cancer has spread) melanoma or renal cell carcinoma.

HD IL-2 is a drug that was designed to help white blood cells regulate their immune response. HD IL-2 is given intravenously (IV, through a needle into a vein). IL-2 is approved by the FDA for the treatment of metastatic renal cell carcinoma and metastatic melanoma.

Nivolumab is a type of drug called a checkpoint inhibitor that was designed to block a protein, allowing the body's immune system to recognize and fight cancer cells. Nivolumab is also given intravenously. Nivolumab is approved by the FDA for the treatment of several cancer types.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 25
• Est. completion date: October 2022
• Est. primary completion date: October 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• At least 6 weeks of prior anti-PD-1 therapy with documented clinical or radiographic progression. Last anti-PD-1 therapy must be within 6 months of enrollment.

• Histologically-confirmed diagnosis of unresectable stage III or metastatic (stage IV) melanoma or renal cell carcinoma

• Measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1, and obtained by imaging within 28 days prior registration for protocol therapy.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Adequate hepatic and renal function

• Female subjects of childbearing potential must have confirmed negative urine or serum pregnancy test prior to drug administration and be willing to use two methods of birth control.

• Male subjects who are not surgically sterile (vasectomy) must agree to use an adequate method of contraception (condoms).

Exclusion Criteria:

• Active infection requiring systemic therapy

• Women who are pregnant or breastfeeding.

• Second active malignancy within the past 5 years with the exception of localized basal or squamous cell skin cancer, in situ cervical or bladder cancer, or localized prostate cancer under active surveillance.

• Active symptomatic central nervous system (CNS) metastases. Prior treated metastases or asymptomatic metastases are allowed. Patient can receive radiation between treatments if deemed medically necessary.

• Surgery within 4 weeks prior to study treatment except for minor procedures.

• Uncontrolled or poorly-controlled hypertension

• Serious or non-healing wounds, ulcers, or bone fractures within 28 days 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.

• Known hypersensitivity to nivolumab or IL-2 or any of their components.

• Known history of active tuberculosis.

• Concurrent systemic steroid therapy with doses above physiologic level (more than 10 mg of prednisone daily)

• Active 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 requiring treatment.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Melanoma
• Metastatic Melanoma
• Renal Cell Carcinoma

Intervention

Drug:
• Nivolumab
480 mg IV of nivolumab on day 1 of the cycle Nivolumab 480 mg IV will be administered day 35
• IL2
Standard HD IL-2 which will be administered every 8 hrs for up to 14 doses days 8-12 and days 22-28 per institutional practice.

Locations

Country	Name	City	State
United States	UC San Diego Moores Cancer Center	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
Mina Nikanjam

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	Complete response and partial response. Response assessment will be performed using revised RECIST guideline (v 1.1).	6 months
Secondary	Incidence of Treatment-Emergent Grade 2-5 Adverse Events assessed using NCI CTCAE v5.0 toxicity criteria		6 months
Secondary	Progression-Free Survival (PFS)	RECIST 1.1 after completion of at least one course of therapy (2 doses of nivolumab, 2 cycles of HD IL-2)	6 months