Clinical trial NCT01946789: A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803 in Patients With Advanced Solid Tumors
Official title: A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803, a Novel Recombinant IL-15 Complex in Patients With Advanced Solid Tumors: Melanoma, Renal Cell, Non-Small Cell Lung and Squamous Cell Head and Neck Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: cancer
IL-15
melanoma
metastatic
unresectable
solid tumors
renal cell
non-small cell lung
squamous cell head and neck
Lead sponsor: Altor BioScience
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-09-20
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The proposed clinical trial is a phase I, open-label, multi-center, dose-escalation study of ALT-803 in patients with surgically incurable advanced solid tumors: melanoma, renal cell, non-small cell lung and squamous cell head and neck cancer

Detailed description: This trial will investigate the safety and immunogenicity, immunomodulatory properties, and clinical benefits of treatment with weekly doses of ALT-803 in patients with advanced solid tumors.

Eligibility criteria: ENTRY CRITERIA:

DISEASE CHARACTERISTICS:

* Histological or cytological confirmed malignancy in the following disease groups: melanoma that is metastatic or unresectable, non-small cell lung carcinoma, renal cell carcinoma or squamous cell head and neck carcinoma, for which standard curative or palliative measures do not exist or are no longer effective.
* Primary site may be cutaneous or unknown, but mucosal and ocular primaries are excluded.
* Patients with non-small lung cancer must have had prior EGFR and ALK testing. Patients with sensitizing mutations in EGFR or ALK rearrangements should have been treated with prior targeted agents and have had progression or discontinued due to toxicity from these agents.
* No patients with known brain metastases.

PRIOR/CONCURRENT THERAPY:

* At least one prior therapy using an agent with the potential for prolonged remission.
* Patients with BRAF v600 mutation should be excluded or may be included after experiencing progression following treatment with BRAF inhibitor regimen or if they consent to forgo FDA-approved therapies that increase median survival.
* At least 4 weeks from last dose of prior chemotherapy or immunomodulator therapy with full recovery of acute toxicities. For patients coming off molecularly-targeted therapy, at least 2 weeks since last dose and recovery from laboratory and constitutional toxicities.
* At least 2 weeks from completion of prior radiation therapy with full recovery from toxicities.
* At least 4 weeks from last dose of prior investigational therapy with recovery to meet baseline eligibility criteria.
* Not receiving any current anticancer therapy
* No patients who have had chemotherapy, targeted therapy, or radiotherapy and have not recovered from acute toxicity to their pretreatment baseline or to a grade 1 level within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. For resolution of autoimmune toxicity from prior immune therapy, patients must be off steroids for at least 30 days without relapse of autoimmune toxicity, or it must be at least 30 days from their last dose of infliximab or related immunosuppressive therapy without relapse of autoimmune toxicity.
* No patients who are receiving any other investigational agents.
* No patients who are receiving chronic systemic or regular inhaled corticosteroid use within 7 days prior to initiation of protocol therapy.
* No immunosuppressive therapy within 30 days prior to treatment start.

PATIENT CHARACTERISTICS

* Age \>18 years
* Both men and women of all races and ethnic groups are eligible.

Performance Status

* ECOG performance status ≤1
* Life expectancy of greater than 6 months.

Bone Marrow Function

* leukocytes ≥3,000/mcL
* absolute lymphocyte count ≥500/mcL
* absolute neutrophil count ≥1,000/mcL (without hematopoietic growth factors)
* platelets ≥100,000/mcL (without transfusion)
* hemoglobin ≥ 10 gm/dL (may be transfused but must be stable without clinical evidence of ongoing blood loss or hemolysis)

Hepatic Function

* total bilirubin within normal institutional limits
* AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

Kidney Function

* Creatinine within normal institutional limits OR
* Creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

Pulmonary Function

• No history of severe COPD or emphysema or interstitial lung disease currently on home supplemental oxygen. Patients with NSCLC with stable COPD or emphysema not requiring supplemental oxygen are eligible.

Cardiac Function

* No symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia. Patients who have underlying risk factors for cardiac disease should be excluded or undergo clearance stress-based cardiac function testing. The pre-treatment QTc must be \<500 msec.
* No class II or greater congestive heart failure as described in the New York Heart Association Functional Classification criteria or serious arrhythmias likely to increase the risk of cardiac complications of cytokine therapy.

Other

* Women of child-bearing potential and men must agree to use adequate contraception.
* Ability to understand and the willingness to sign a written informed consent document.
* No uncontrolled inter-current illness or psychiatric illness/social situations that would limit compliance with study requirements.
* No pregnant women.
* No HIV-positive patients.
* No positive hepatitis C serology or active hepatitis B infection.
* No active bacterial or fungal infection.
* No inability to home monitor blood pressure.
* Patients with thyroid disease should be excluded unless euthyroid on suppressive or replacement therapy.

Primary outcomes:
measure: Dose Limiting Toxicity
timeFrame: 9 months
Secondary outcomes:
measure: Number of Participants Who Developed Anti-drug Antibodies to ALT-803
timeFrame: 14 days post final dose, up to 135 days
measure: To Evaluate the Effect of Escalating Doses of ALT-803: Pharmacokinetics (Half Life and Tmax)
timeFrame: 24 hours post dose
measure: To Evaluate the Effect of Escalating Doses of ALT-803: Pharmacokinetics (Cmax)
timeFrame: 24 hours after first dose
measure: To Evaluate the Effect of Escalating Doses of ALT-803: Pharmacokinetics (AUC 0-t, AUC0-24, AUC0-infinity)
timeFrame: 24 hours after first dose
measure: To Evaluate the Effect of Escalating Doses of ALT-803: Interferon Gamma (IFN-γ)
timeFrame: Cycle 1 Week 1, pre-dose; Cycle 1 Week 1, 30 minutes post dose; Cycle 1 Week 1, 2 hours post dose; Cycle 1 Week 1, 4 hours post dose; Cycle 1 Week 1, 8 hours post dose; Cycle 1 Week 1, 24 hours post dose
measure: Objective Response Rate
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Seattle
country: United States
facility: University of Washington, Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Roswell Park Cancer Institute
name: Marc Ernstoff, MD
role: PRINCIPAL_INVESTIGATOR
References: