Clinical trial NCT01209676: IMCgp100 in Advanced Unresectable Melanoma
Official title: A Phase 0, Exploratory Study of the Pharmacodynamics of a Single Intratumoral Dose of IMCgp100, a Monoclonal Receptor Anti-CD3 scFv Fusion Protein, in Subjects With Advanced Unresectable Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Melanoma
Advanced Disease
Unresectable
Keywords: melanoma, with advanced unresectable
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2010-09-27
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A phase 0, exploratory study of the pharmacodynamics of a single intratumoral dose of IMCgp100, a monoclonal T cell receptor anti-CD3 scFv fusion protein, in subjects with advanced unresectable melanoma to assess the safety and pharmacodynamic properties of single intratumoral doses of IMCgp100 in the setting of advanced unresectable melanoma. Six patients will be enrolled to complete the study over approximately 12-15 months.

Detailed description: This study will test the safety effect of a single dose of the investigational drug IMCgp100 when administered directly into the metastatic melanoma lesion in patients with advanced metastatic melanoma. IMCgp100 is a drug made up of two components. The first is the T cell receptor designed to bind specifically and tightly with protein found at high levels on the surface of melanoma cancer cells and second is an anti-CD3 fragment that is meant to bind to and activate the T cells. There will be two stage dose regimens each enrolling 3 patients. Stage 1 dose will 0.00017 mg IMCgp100 and Stage 2 dose will be 0.0017 mg IMCgp100. Inclusion Criteria: 1. Histologically confirmed dx of advanced unresectable melanoma not requiring immediate treatment and/or in a window between treatments 2. Two or more cutaneous or subcutaneous melanoma metastatic lesions 7 to 15 mm in at least one dimension and amenable to subsequent biopsy 3. Greater or equal to 18 years of age 4. ECOG PS 0-2 5.

Able to provide informed consent and willing to comply with protocol requirements 6. Female patients must not be of childbearing potential or must have negative serum pregnancy test 48 hours prior to receiving investigational drug 7. Male patients must agree to use reliable form of birth control throughout study 8. Must have adequate organ system function Exclusion Criteria: 1. Received any other chemo, immune, radiation or investigational therapy agents within 2 weeks prior to study treatment 2. Cutaneous metastasis that have received prior local therapy 3. Pregnant or breastfeeding 4.

History of autoimmune disease 5. Current treatment with steroid or other immunosuppressive meds 6. Active uncontrolled infection 7. Known HIV infection 8. Uncontrolled seizures 9. Known delayed wound healing 10. On full dose anticoagulation therapy.

Eligibility criteria: Inclusion Criteria:

* 1. Histologically confirmed diagnosis of melanoma, with advanced unresectable disease not currently requiring immediate treatment and/or in a window between treatments.
* 2. Two or more cutaneous or subcutaneous melanoma metastatic lesions 7-15 mm in at least one dimension and amenable to subsequent biopsy.
* 3. Age 18 years
* 4. ECOG performance status 0-2
* 5. Able to understand and to provide written informed consent and willingness to comply with all protocol requirements;
* 6. Female patients who are not be of childbearing potential as documented by medical history (e.g., tubal ligation or hysterectomy), or be post menopausal with a minimum 1 year without menses or have a negative serum beta human chorionic gonadotropin (HGC) pregnancy test within 48 hours prior to receiving the intratumoral injection and agree to use an acceptable form of birth control, defined as abstinence or use of an intrauterine device (IUD), oral contraceptive, barrier and spermicide, or hormonal implant throughout the study period;
* 7. Male patients who must agree to use an acceptable form of birth control throughout the study period.
* 8. Adequate organ system function as evidenced by laboratory values: -Absolute neutrophil count (ANC) greater than or equal to 1.0 X 109/L -Hemoglobin greater than or equal to 9 g/dL -Platelets greater than or equal to 75 X 109/L -Total bilirubin less than or equal to 1.5 mg/dL -AST and ALT less than or equal to 2.5 X ULN ( 2.5 X ULN in the presence of liver metastasis.) -Creatinine less than or equal to 2 mg/dL -TSH within normal limits -INR/PT and PTT less than or equal to 1.3 X ULN

Exclusion Criteria:

* 1. Receive any chemotherapy, immunotherapy, radiation therapy, or other investigational agents (agents part of a research protocol or not approved by the FDA) within 2 weeks prior to injection. A minimum of 14 days is required between last therapy and injection on this study. In addition, any clinically significant drug-related toxicity should have recovered to grade 1 or less (excluding alopecia)
* 2. Patients without cutaneous or subcutaneous metastatic lesions;
* 3. Cutaneous metastases that have received prior local therapy, such as radiation or isolated limb perfusion.
* 4. Pregnancy or breastfeeding
* 5. History of autoimmune disease (excluding vitiligo or controlled thyroid disease) or immunodeficiency.
* 6. Current treatment with steroids (inhaled, topical or systemic) or other immunosuppressive medications within 2 weeks of injection;
* 7. Active uncontrolled infection;
* 8. Known HIV positivity;
* 9. Uncontrollable seizures;
* 10. Known delayed wound healing;
* 11. Full dose anticoagulation with heparin, warfarin, or any other anticoagulant within 2 weeks of injection ;
* 12. History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting, stroke or TIA within the past 24 weeks.;
* 13. Known hypersensitivity of IMCgp100 or any of its components (ie, Tween) ;
* 14. Class II, III, or IV heart failure as defined by the New York Heart Association;
* 15. Any psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
* 16. Any other condition that in the investigators opinion would jeopardize compliance with the protocol ;

Primary outcomes:
measure: Adverse Events as a Measure of Safety and Tolerability
timeFrame: 15 months
Secondary outcomes:
measure: Adverse events
timeFrame: 15 months
measure: Vital signs
timeFrame: 15 months
measure: PE examinations findings
timeFrame: 15 months
measure: Peripheral blood samples
timeFrame: 15 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Abramson Cancer Center at Penn Medicine
name: Giorgos Karakousis, MD
role: PRINCIPAL_INVESTIGATOR
References: