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A Phase 1 Study of Recombinant Human IL15 (rhIL15) in Adults With Advanced Solid Tumors: Melanoma, Renal Cell, Non-Small Cell Lung and Head and Neck Cancer


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Basal Cell Carcinoma of the Lip, Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Recurrent Lymphoepithelioma of the Nasopharynx, Recurrent Lymphoepithelioma of the Oropharynx, Recurrent Melanoma, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Recurrent Mucoepidermoid Carcinoma of the Oral Cavity, Recurrent Non-small Cell Lung Cancer, Recurrent Renal Cell Cancer, Recurrent Salivary Gland Cancer, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Recurrent Verrucous Carcinoma of the Larynx, Recurrent Verrucous Carcinoma of the Oral Cavity, Stage III Adenoid Cystic Carcinoma of the Oral Cavity, Stage III Basal Cell Carcinoma of the Lip, Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage III Lymphoepithelioma of the Nasopharynx, Stage III Lymphoepithelioma of the Oropharynx, Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage III Mucoepidermoid Carcinoma of the Oral Cavity, Stage III Renal Cell Cancer, Stage III Salivary Gland Cancer, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage III Squamous Cell Carcinoma of the Nasopharynx, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage III Verrucous Carcinoma of the Larynx, Stage III Verrucous Carcinoma of the Oral Cavity, Stage IIIA Melanoma, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Melanoma, Stage IIIB Non-small Cell Lung Cancer, Stage IIIC Melanoma, Stage IV Lymphoepithelioma of the Nasopharynx, Stage IV Melanoma, Stage IV Non-small Cell Lung Cancer, Stage IV Renal Cell Cancer, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVA Basal Cell Carcinoma of the Lip, Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IVA Lymphoepithelioma of the Oropharynx, Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVA Salivary Gland Cancer, Stage IVA Squamous Cell Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVA Verrucous Carcinoma of the Larynx, Stage IVA Verrucous Carcinoma of the Oral Cavity, Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVB Basal Cell Carcinoma of the Lip, Stage IVB Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IVB Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IVB Lymphoepithelioma of the Oropharynx, Stage IVB Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVB Salivary Gland Cancer, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVB Verrucous Carcinoma of the Larynx, Stage IVB Verrucous Carcinoma of the Oral Cavity, Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVC Basal Cell Carcinoma of the Lip, Stage IVC Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IVC Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IVC Lymphoepithelioma of the Oropharynx, Stage IVC Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVC Salivary Gland Cancer, Stage IVC Squamous Cell Carcinoma of the Larynx, Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVC Squamous Cell Carcinoma of the Oropharynx, Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVC Verrucous Carcinoma of the Larynx, Stage IVC Verrucous Carcinoma of the Oral Cavity, Tongue Cancer

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Trial Information

A Phase 1 Study of Recombinant Human IL15 (rhIL15) in Adults With Advanced Solid Tumors: Melanoma, Renal Cell, Non-Small Cell Lung and Head and Neck Cancer


PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of recombinant human IL15 (recombinant
interleukin-15) (rhIL15) administered subcutaneous.

SECONDARY OBJECTIVES:

I. To determine the effect of the dose schedules of rhIL15 on the number and phenotype of
peripheral blood mononuclear cells including total white blood cell count, absolute
lymphocyte count (ALC), total number of T cells and natural killer (NK) cells, as well as
activated T cells, T cell subsets and NK cell subsets.

II. To determine the effect of the dose schedules of rhIL15 on the function of peripheral
blood mononuclear cells including T cell subset response to recall viral antigens including
cytomegalovirus (CMV) and influenza A virus, T cell responses to non- physiologic stimuli
including: phytohemagglutinin (PHA), and NK cell cytokine (interferon gamma [IFN-y])
secretion and degranulation by cluster of differentiation 107a (CD107a) expression.

III. To assess tumor response rate by objective response rate (ORR). IV. To assess the
immunogenicity, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of National Cancer
Institute (NCI) rhIL15.

OUTLINE: This is a dose-escalation study.

Patients receive recombinant interleukin-15 subcutaneously (SC) daily on days 1-5 and 8-12.
Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed up for 24 weeks.


Inclusion Criteria:



- Patients must have histological or cytological confirmed malignancy in the following
disease groups: melanoma, non-small cell lung carcinoma, renal cell carcinoma or head
and neck carcinoma, for which no standard effective or curative options are available

- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

- Documented evidence of disease progression during 6 month period prior to the time of
enrollment

- Prior therapy requirements:

- At least >= 1 prior completed chemotherapy regimen

- At least 4 weeks from last dose of prior chemotherapy with resolution of the
acute toxic effects of the therapy

- At least 2 weeks from completion of prior radiation therapy

- At least 4 weeks from last dose of prior investigational therapy

- Not receiving any current anti-cancer therapy

- At least 4 weeks from last dose of interferon or interleukin (IL)-2 therapy

- At least 12 weeks from completion of antibody therapy with anti-checkpoint
antibodies, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and
anti-programmed cell death 1 (PD1)

- At least 4 weeks from last dose of prior other biologic agents

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky >=
70%)

- Absolute lymphocytes >= 800/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin within normal institutional limits

- Prothrombin time (PT)/partial thromboplastin time (PTT) =< 1.5 x upper limit of
normal (ULN)

- Hemoglobin (Hgb) >= 10 g/dL

- Alkaline phosphatase =< 2.5 x ULN

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2 x institutional upper limit of normal

- Serum creatinine < 1.5 x ULN or creatinine clearance > 60 mL/min/1.73 m2 for patients
with creatinine levels above institutional normal

- Thyroid function thyroxine (T4), thyroid stimulating hormone (TSH) within normal
limits; pre-existing hypothyroidism is acceptable as long as patient has been stable
on thyroid replacement for four months prior to entering the study

- No known central nervous system (CNS) metastases or neurological symptoms possibly
related to active CNS metastasis

- Females of childbearing potential must have a negative pregnancy test within 48 hours
prior to initiation of protocol therapy; note: subjects are considered not of child
bearing potential if they are surgically sterile, they have undergone a hysterectomy,
bilateral tubal ligation, or bilateral oophorectomy or they are postmenopausal;
menopause is the age associated with complete cessation of menstrual cycles, menses,
and implies the loss of reproductive potential; by a practical definition, it assumes
menopause after 1 year without menses with an appropriate clinical profile at the
appropriate age

- Ability to understand and the willingness to sign a written informed consent document

- No history of any hematopoietic malignancy

- No active (as defined by requiring immunosuppressive therapy) or history of
clinically significant autoimmune disease (as defined by previously requiring
immunosuppressive therapy)

- No evidence of a clinically significant active infection

- No systemic or inhaled corticosteroids or immunosuppressive therapy within 30 days
prior to initiation of protocol therapy; note: use of topical corticosteroids and/or
eye drops containing glucocorticosteroids is acceptable

- No history of severe asthma, as defined by prior or current use of systemic
corticosteroids for disease control, with the exception of physiological replacement
doses of cortisone acetate or equivalent, as defined by a dose of 10mg or less; note:
history of mild asthma not requiring daily therapy is eligible

- No history of pulmonary disease such as emphysema or chronic obstructive pulmonary
disease (COPD), (forced expiratory volume in one second [FEV1] >= 2L or >= 75% of
predicted for height and age); pulmonary function tests (PFTs) are required in
patients with significant pulmonary or smoking history

- No history of human immunodeficiency virus (HIV), active or chronic hepatitis B,
hepatitis C or human T-cell lymphotropic virus (HTLV-I) infection; note: a positive
hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface
antibody [HBsAb] positive and hepatitis B core antibody [HBcAb] negative), or a fully
resolved acute hepatitis B virus (HBV) infection is not an exclusion criterion

- Females of childbearing potential and males must be willing to use an effective
method of contraception (hormonal, barrier method of birth control or abstinence)
from the time the consent is signed, during the duration of study participation and 4
months after discontinuation of protocol therapy

- Females must not be breastfeeding

- No evidence of clinically significant congestive heart failure, (ejection fraction of
45% or greater)

- No platelet or blood transfusions within two weeks of obtaining baseline laboratory
values

- No blood modifiers while enrolled in the study (growth factors such as
erythropoiesis-stimulating agent [ESA], filgrastim [G-CSF], platelet or blood
transfusions)

Exclusion Criteria:

- Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or
mitomycin C), or radiotherapy within 2 weeks prior to entering the study or those who
have not recovered from adverse events due to agents administered more than 4 weeks
earlier

- Class II or greater congestive heart failure as described in the New York Heart
Association Functional Classification criteria

- Patients with primary brain cancer or known brain metastases should be excluded from
this clinical trial

- Patients who have received prior anti-CTLA4 or anti-PD1 therapy less than 12 weeks
prior to enrollment

- Patients who have received prior biologic agents less than 4 weeks prior to
enrollment

- Patients who have received prior interferon or IL-2 therapy less than 4 weeks prior
to enrollment

- Patients who are receiving any other investigational agents

- ECOG score greater than 1 (Karnofsky < 70%)

- HIV-positive patients

- Positive hepatitis C serology

- Inability to home monitor blood pressure

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD defined as the next lower dose in which 1 or more patients experiences a dose limiting toxicity (DLT) defined as grade 3 or 4 toxicity graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Outcome Time Frame:

28 days

Safety Issue:

Yes

Principal Investigator

Jeffrey Miller

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer Immunotherapy Trials Network

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02205

NCT ID:

NCT01727076

Start Date:

February 2013

Completion Date:

Related Keywords:

  • Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
  • Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
  • Recurrent Basal Cell Carcinoma of the Lip
  • Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
  • Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
  • Recurrent Lymphoepithelioma of the Nasopharynx
  • Recurrent Lymphoepithelioma of the Oropharynx
  • Recurrent Melanoma
  • Recurrent Metastatic Squamous Neck Cancer With Occult Primary
  • Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
  • Recurrent Mucoepidermoid Carcinoma of the Oral Cavity
  • Recurrent Non-Small Cell Lung Cancer
  • Recurrent Renal Cell Cancer
  • Recurrent Salivary Gland Cancer
  • Recurrent Squamous Cell Carcinoma of the Hypopharynx
  • Recurrent Squamous Cell Carcinoma of the Larynx
  • Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Recurrent Squamous Cell Carcinoma of the Nasopharynx
  • Recurrent Squamous Cell Carcinoma of the Oropharynx
  • Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Recurrent Verrucous Carcinoma of the Larynx
  • Recurrent Verrucous Carcinoma of the Oral Cavity
  • Stage III Adenoid Cystic Carcinoma of the Oral Cavity
  • Stage III Basal Cell Carcinoma of the Lip
  • Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
  • Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
  • Stage III Lymphoepithelioma of the Nasopharynx
  • Stage III Lymphoepithelioma of the Oropharynx
  • Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
  • Stage III Mucoepidermoid Carcinoma of the Oral Cavity
  • Stage III Renal Cell Cancer
  • Stage III Salivary Gland Cancer
  • Stage III Squamous Cell Carcinoma of the Hypopharynx
  • Stage III Squamous Cell Carcinoma of the Larynx
  • Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage III Squamous Cell Carcinoma of the Nasopharynx
  • Stage III Squamous Cell Carcinoma of the Oropharynx
  • Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage III Verrucous Carcinoma of the Larynx
  • Stage III Verrucous Carcinoma of the Oral Cavity
  • Stage IIIA Melanoma
  • Stage IIIA Non-Small Cell Lung Cancer
  • Stage IIIB Melanoma
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IIIC Melanoma
  • Stage IV Lymphoepithelioma of the Nasopharynx
  • Stage IV Melanoma
  • Stage IV Non-Small Cell Lung Cancer
  • Stage IV Renal Cell Cancer
  • Stage IV Squamous Cell Carcinoma of the Hypopharynx
  • Stage IV Squamous Cell Carcinoma of the Nasopharynx
  • Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity
  • Stage IVA Basal Cell Carcinoma of the Lip
  • Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
  • Stage IVA Lymphoepithelioma of the Oropharynx
  • Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
  • Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity
  • Stage IVA Salivary Gland Cancer
  • Stage IVA Squamous Cell Carcinoma of the Larynx
  • Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVA Squamous Cell Carcinoma of the Oropharynx
  • Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVA Verrucous Carcinoma of the Larynx
  • Stage IVA Verrucous Carcinoma of the Oral Cavity
  • Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity
  • Stage IVB Basal Cell Carcinoma of the Lip
  • Stage IVB Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVB Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
  • Stage IVB Lymphoepithelioma of the Oropharynx
  • Stage IVB Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
  • Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity
  • Stage IVB Salivary Gland Cancer
  • Stage IVB Squamous Cell Carcinoma of the Larynx
  • Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVB Squamous Cell Carcinoma of the Oropharynx
  • Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVB Verrucous Carcinoma of the Larynx
  • Stage IVB Verrucous Carcinoma of the Oral Cavity
  • Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity
  • Stage IVC Basal Cell Carcinoma of the Lip
  • Stage IVC Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVC Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
  • Stage IVC Lymphoepithelioma of the Oropharynx
  • Stage IVC Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
  • Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity
  • Stage IVC Salivary Gland Cancer
  • Stage IVC Squamous Cell Carcinoma of the Larynx
  • Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVC Squamous Cell Carcinoma of the Oropharynx
  • Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVC Verrucous Carcinoma of the Larynx
  • Stage IVC Verrucous Carcinoma of the Oral Cavity
  • Tongue Cancer
  • Carcinoma
  • Carcinoma, Basal Cell
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Renal Cell
  • Carcinoma, Squamous Cell
  • Carcinoma, Adenoid Cystic
  • Granuloma
  • Head and Neck Neoplasms
  • Laryngeal Diseases
  • Lung Neoplasms
  • Melanoma
  • Papilloma
  • Tongue Neoplasms
  • Carcinoma, Mucoepidermoid
  • Carcinoma, Verrucous
  • Esthesioneuroblastoma, Olfactory
  • Papilloma, Inverted
  • Neoplasms, Unknown Primary
  • Salivary Gland Neoplasms
  • Hypopharyngeal Neoplasms
  • Laryngeal Neoplasms
  • Paranasal Sinus Neoplasms
  • Oropharyngeal Neoplasms
  • Nasopharyngeal Neoplasms

Name

Location

University of Washington Medical CenterSeattle, Washington  98195-6043
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
National Institutes of HealthBethesda, Maryland  20892
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
Stanford University Hospitals and ClinicsStanford, California  94305