Clinical trial NCT03157167: An Evaluation of Tc 99m Tilmanocept by Intravenous (IV) and Subcutaneous (SC) Injection in Kaposi Sarcoma (KS)
Official title: An Evaluation of the Safety of Escalating Doses of Tc 99m Tilmanocept by Intravenous (IV) Injection and a Comparison to Subcutaneous (SC) Injection in Human Immunodeficiency Virus (HIV) Subjects Diagnosed With Kaposi Sarcoma (KS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Kaposi Sarcoma
HIV Infections
Keywords: Kaposi Sarcoma, KS, HIV
Lead sponsor: Navidea Biopharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2017-05-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: DIAGNOSTIC

Brief summary: To determine the safety of escalating IV doses of Tc 99m tilmanocept in HIV (human immunodeficiency virus) subjects with confirmed KS and to compare results obtained from subcutaneous and IV administrations of Tc 99m tilmanocept in the same subjects.

Detailed description: This is a Manocept Platform prospective, single-center, open-label, non-randomized, dose escalation, comparative, safety study of intravenously and subcutaneously injected Tc 99m tilmanocept in the localization and detection of cutaneous and non-cutaneous KS tumor(s) in subjects with biopsy-confirmed KS. Three IV doses (µg/mCi) of tilmanocept will be evaluated in three cohort groups. One subcutaneous dose will be evaluated in cohort group 3.

This study is designed to evaluate the safety and tolerability of escalating doses of IV Tc 99m tilmanocept and to compare results obtained from IV and subcutaneous administrations of Tc 99m tilmanocept in the same subjects. Whole body planar as well as SPECT/CT imaging will be performed to provide greater resolution of areas of Tc 99m tilmanocept localization. A biopsy of a non-visceral KS lesion will be taken to correlate pathology with Tc 99m tilmanocept localization.

This study is designed to evaluate the use of Tc 99m tilmanocept as an imaging agent in HIV-positive subjects with known KS by evaluating localization in known and unknown cutaneous and non-cutaneous lesions.

Eligibility criteria: Inclusion Criteria:

1. The subject has provided written informed consent with HIPAA authorization before the initiation of any study-related procedures.
2. The subject is at least 18 years of age at the time of consent.
3. The subject is HIV positive.
4. The subject has a biopsy-confirmed diagnosis of KS and is classified into one of the categories below:

   1. Confirmed cutaneous KS/oral lesions without edema.
   2. Confirmed cutaneous KS/oral lesions with edema.
   3. Confirmed cutaneous KS/oral lesions with or without edema and suspected non-cutaneous KS due to clinical symptomology or confirmed non-cutaneous KS lesion(s).

Exclusion Criteria:

1. The subject is pregnant or lactating.
2. The subject has received chemotherapy or radiation therapy to KS sites within six weeks of enrollment.
3. The subject has known sensitivity to dextran.
4. The subject has received an investigational product within 30 days prior to the Tc 99m tilmanocept administration on Day 1.
5. The subject has received any radiopharmaceutical within 7 days prior to the administration of Tc 99m tilmanocept on Day 1.
6. Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.

Primary outcomes:
measure: To Determine the Safety of Escalating Doses of Tc 99m Tilmanocept in HIV Subjects With Biopsy-confirmed KS.
timeFrame: 10 days after IV Tc 99m tilmanocept administration
Secondary outcomes:
measure: Per Subject Localization Rate of Tc 99m Tilmanocept in at Least One KS Suspected or Confirmed Lesion by Planar and/or SPECT/CT Imaging
timeFrame: 10 days after IV Tc 99m tilmanocept administration
measure: Qualify and Quantify Tc 99m Tilmanocept Localization Intensity on Imaging With CD206 Locale and Quantity by Histology and IHC in Biopsied KS Lesions to Determine Optimal IV Dose.
timeFrame: 10 days after IV Tc 99m tilmanocept administration
measure: Localization Concordance of Subcutaneous Injection and IV Injection
timeFrame: 10 days after IV Tc 99m tilmanocept administration
measure: Exploratory: Quantify HHV8 in Biopsied KS Lesions. Mean and Standard Deviation Results.
timeFrame: 10 days after IV Tc 99m tilmanocept administration
measure: Exploratory: Quantify HHV8 in Biopsied KS Lesions. Median Results.
timeFrame: 10 days after IV Tc 99m tilmanocept administration
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital
state: California
Study officials:
affiliation: Navidea Biopharmaceuticals
name: Michael Blue, MD
role: STUDY_DIRECTOR
References:
citation: Cope, F.O., W. Metz, et al. Innovations in receptor-targeted precision imaging at Navidea: diagnosis up close and personal. Nature Outlook (31 October 2013); S125-S129.
citation: Cope FO, Abbruzzese B, Sanders J, Metz W, Sturms K, Ralph D, Blue M, Zhang J, Bracci P, Bshara W, Behr S, Maurer T, Williams K, Walker J, Beverly A, Blay B, Damughatla A, Larsen M, Mountain C, Neylon E, Parcel K, Raghuraman K, Ricks K, Rose L, Sivakumar A, Streck N, Wang B, Wasco C, Williams A, Schlesinger LS, Azad A, Rajaram MVS, Jarjour W, Young N, Rosol T, McGrath M. Corrigendum to the inextricable axis of targeted diagnostic imaging and therapy: An immunological natural history approach [Nucl Med Biol 43 (2016) 215-225]. Nucl Med Biol. 2016 Dec;43(12):837. doi: 10.1016/j.nucmedbio.2016.10.001. No abstract available.