NHS-IL12 for Solid Tumors

NCT01417546 | Completed Phase 1 FDA Drug

• 2 other identifiers: 11022511-C-0225
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- The experimental drug NHS-IL12 may help the immune system become more active and kill cancer cells that have not responded to standard treatments. NHS-IL12 has been designed to cause less severe side effects than other anticancer drugs, and may be more effective. More research is needed to test NHS-IL12 in people who have solid tumors that have not responded to treatment. Objectives: \- To test the safety and effectiveness of NHS-IL12 as a treatment for solid tumors which have not responded to standard treatments. Eligibility: \- Individuals at least 18 years of age with solid tumors that have not responded to standard treatments. Design:

• Participants will be screened with a medical history, physical exam, blood and urine tests, and imaging studies.
• Participants will receive NHS-IL12 injection every 4 weeks, and will stay in the hospital for at least one day to be monitored with frequent blood tests.
• Participants will have periodic blood samples taken before treatment and during the first week after treatment for the first two cycles. They will then have blood samples taken before treatment for the rest of the cycles.

Conditions

Epithelial Neoplasms, Malignant; Epithelial Tumors, Malignant; Malignant Mesenchymal Tumor

Keywords

Maximum Tolerated Dose; Immune Response; Pharmacokinetics; Dose Escalation; Dose Limited Toxicity

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicities (DLTs) and Maximum Tolerated Dose (MTD)

  Determination of DLTs and MTD.

  During the first 6 weeks or at least 2 weeks after administration of the second dose.

Secondary Outcomes (1)

• To determine immunogenicity, safety and pharmacokinetic parameters

  Ongoing

Study Arms (3)

1

EXPERIMENTAL

NHS-IL12 escalating doses on a 4 week schedule (Completed).

Drug: NHS-IL-12

2

EXPERIMENTAL

NHS-IL12 escalating doses on a 2 week schedule

Drug: NHS-IL-12

3

EXPERIMENTAL

NHS-IL12 expansion group on a 4 week schedule (Completed).

Drug: NHS-IL-12

Interventions

NHS-IL-12 DRUG

NHS-IL12 is an investigational agent supplied to investigators by the manufacturer EMD Serono, Inc.

1; 2; 3

Eligibility Criteria

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

You may qualify if:

• Participants must meet the following criteria for participation:
• Participants must have histologically confirmed malignancy that is metastatic or unresectable locally advanced solid tumors.
• Participants must have completed or had disease progression on at least one prior line of disease-appropriate therapy for unresectable locally advanced or metastatic disease, or not be a candidate for therapy of proven efficacy for their disease due to an underlying physical condition.
• Participants may have disease that is measurable or non-measurable but evaluable disease (e.g. present on bone scan, rising tumor markers, non-measurable by RECIST but visible on CT scan). Participants with third space fluid (for example pleural effusions) as only site of disease will not be eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at study entry.
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of NHS-IL12 in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Participants must have normal organ and marrow function as defined below:
• Hematological eligibility parameters (within 16 days of starting therapy):
• Absolute granulocyte count greater than or equal to 1,500/mcL
• Absolute lymphocyte count greater than or equal to 500/mcL
• Platelet count greater than or equal to 100,000/mcL
• hemoglobin greater than or equal to 9 g/dL
• Adequate hepatic function defined by a
• total bilirubin level less than or equal to 1.5 times ULN or in participants with Gilbert s syndrome, a total bilirubin less than or equal to 3.0, and
• aspartate aminotransferase (AST) and alanine-aminotransferase (ALT) levels less than or equal to 2.5 times ULN or, for participants with documented metastatic disease to the liver, AST and ALT levels less than or equal to 5 times ULN.

You may not qualify if:

• Participants with any of the following will not be eligible for participation in this study:
• Participants who are receiving any other investigational concurrent anticancer treatment (chemotherapy, radiotherapy, immunotherapy, cytokine therapy except erythropoietin) at the time of enrollment except for disease specific appropriate hormonal therapies (e.g., ADT for prostate cancer, anti-estrogen for breast cancer, somatostatin analogue for neuroendocrine cancer)
• Concurrent use of systemic steroids (within 10 days of enrollment) will be excluded, except for physiologic doses of systemic steroid replacement or local (topical, nasal, or inhaled) steroid use. Limited doses of systemic steroids (e.g., in participants with exacerations of reactive airway disease) must have completed at least 10 days prior to enrollment. Steroid use to prevent IV contrast allergic reaction or anaphylaxis in participants who have known contrast allergies is allowed at any time prior to enrollment.
• Participants who have previously received rIL-12
• Acquired immune defects such as HIV or innate immunodeficiency because this agent requires an intact immune system. In addition, these participants are at increased risk of lethal infections when treated with marrow-altering therapy.
• Systemic autoimmune disease (e.g., lupus erythematosus, rheumatoid arthritis, Addison s disease, autoimmune disease associated with lymphoma).
• History of organ transplant.
• History of or active inflammatory bowel disease (e.g., Crohn s disease, ulcerative colitis).
• Chronic infections (e.g., hepatitis B or C, tuberculosis).
• Known hypersensitivity or allergic reactions attributed to any compounds of similar chemical or biologic composition to the study medication, such as recombinant IL-12 or other monoclonal antibodies
• Known hypersensitivity to methotrexate
• History of brain metastases because of the poor prognosis of participants with brain metastases and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke \< 6 months prior to enrollment, myocardial infarction \< 6 months prior to enrollment, unstable angina, congestive heart failure (greater than or equal to NYHA III) or serious cardiac arrhythmia requiring medication.
• Pulmonary disease which, in the opinion of the investigator, may impair the patient s respiratory tolerance to moderate pulmonary fluid overload (e.g., interstitial lung disease, severe chronic obstructive pulmonary disease).
• All conditions associated with significant necrosis of nontumor-bearing tissues: esophageal or gastroduodenal ulcers \< 6 months prior to enrollment, organ infarction \< 6 months prior to enrollment, or active ischemic bowel disease.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Portielje JE, Kruit WH, Schuler M, Beck J, Lamers CH, Stoter G, Huber C, de Boer-Dennert M, Rakhit A, Bolhuis RL, Aulitzky WE. Phase I study of subcutaneously administered recombinant human interleukin 12 in patients with advanced renal cell cancer. Clin Cancer Res. 1999 Dec;5(12):3983-9.

  PMID: 10632329 BACKGROUND

• Mortarini R, Borri A, Tragni G, Bersani I, Vegetti C, Bajetta E, Pilotti S, Cerundolo V, Anichini A. Peripheral burst of tumor-specific cytotoxic T lymphocytes and infiltration of metastatic lesions by memory CD8+ T cells in melanoma patients receiving interleukin 12. Cancer Res. 2000 Jul 1;60(13):3559-68.

  PMID: 10910069 BACKGROUND

• Gollob JA, Mier JW, Veenstra K, McDermott DF, Clancy D, Clancy M, Atkins MB. Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response. Clin Cancer Res. 2000 May;6(5):1678-92.

  PMID: 10815886 BACKGROUND

• Gatti-Mays ME, Tschernia NP, Strauss J, Madan RA, Karzai FH, Bilusic M, Redman J, Sater HA, Floudas CS, Toney NJ, Donahue RN, Jochems C, Marte JL, Francis D, McMahon S, Lamping E, Cordes L, Schlom J, Gulley JL. A Phase I Single-Arm Study of Biweekly NHS-IL12 in Patients With Metastatic Solid Tumors. Oncologist. 2023 Apr 6;28(4):364-e217. doi: 10.1093/oncolo/oyac244.

  PMID: 36640137 DERIVED

• Bekaii-Saab T, Wesolowski R, Ahn DH, Wu C, Mortazavi A, Lustberg M, Ramaswamy B, Fowler J, Wei L, Overholser J, Kaumaya PTP. Phase I Immunotherapy Trial with Two Chimeric HER-2 B-Cell Peptide Vaccines Emulsified in Montanide ISA 720VG and Nor-MDP Adjuvant in Patients with Advanced Solid Tumors. Clin Cancer Res. 2019 Jun 15;25(12):3495-3507. doi: 10.1158/1078-0432.CCR-18-3997. Epub 2019 Feb 25.

  PMID: 30804020 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma; Malignant mesenchymal tumor

Interventions

NHS-IL12 immunocytokine

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• James L Gulley, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2011
• First Posted: August 16, 2011
• Study Start: December 12, 2011
• Primary Completion: June 2, 2021
• Study Completion: October 14, 2021
• Last Updated: October 18, 2021

Record last verified: 2021-10

Locations

US (1)