NCT03188328

Safety, Tolerability, PK, Dosimetry, MTD and Preliminary Efficacy of Intra-lesionally Injected AvidinOX, Followed by IV Escalating Doses of [177Lu]DOTA-biotin in Pts With Injectable Solid Tumors or Lymphomas

A Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, Dosimetry, Maximum Tolerated Dose and Preliminary Efficacy of Intra-lesionally Injected AvidinOX, Followed by Systemic IV Administration of Escalating Doses of [177Lu]DOTA-biotin in Patients With Solid Tumors or Lymphomas With Injectable Neoplastic Lesions.

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: Alfasigma S.p.A. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Local treatment of unresectable tumors is challenging, particularly with radioactivity. Current practice relies on external beam irradiation or on a variety of medical devices for brachytherapy. Both approaches proved useful in controlling tumor growth but are characterized by poor patient's compliance, significant side effects, high costs and technological complexity hampering wide-spread use. The use of AvidinOX for radionuclide therapy of inoperable cancer lesions will offer a number of advantages compared to current brachytherapy. In fact, the perfusion of a target tissue with AvidinOX, compared to current devices, will allow adapting the therapy to the tumor/organ shape, and it will also make it possible to delay the administration of radioactivity for several days which, according to pre-clinical studies, might be also divided up into repeated doses. AvidinOX linking stably to tissue proteins, does not exhibit the problem of seed migration which is associated with high morbidity. Based on previous findings with AvidinOX in combination with radionuclides in pre-clinical studies as well as data from the clinical use in liver metastases, it can be assumed that intralesional injections of AvidinOX followed by intravenous injections of 177Lu-ST2210 could be a safe and efficacious method for treating inoperable tumor lesions.

Detailed description

The primary objectives of this study are: 1. To identify the Maximum Tolerated Dose (MTD) of two consecutive repeated IV 177Lu-ST2210 administration following a previous tumor intra-lesion/s injection of AvidinOX. 2. To assess safety and tolerability of intra-lesionally injected AvidinOX + IV injected 177Lu-ST2210 3. To evaluate intra-lesional distribution and retention of {AvidinOX + 177Lu-ST2210}-complex in tumor lesion/s 4. To evaluate systemic biodistribution and pharmacokinetics of 177Lu-ST2210 and {AvidinOX + 177Lu-ST2210}- complex Main secondary objectives are: 1. To evaluate whole body dosimetry of IV 177Lu-ST2210 after prior AvidinOX injection (radiation safety dosimetry) 2. To record individual tumor dosimetry 3. To evaluate preliminary efficacy of {AvidinOX + 177Lu-ST2210}-complex in reducing tumor size and metabolic activity. 4. To evaluate damage of tumor cells by radioactivity and immunogenic cell death 5. To evaluate whole body safety dosimetry and dose linearity 6. To evaluate pharmacokinetics of ST2210 in plasma and urine

Conditions

• Inoperable Solid Tumors or Lymphomas

Interventions

Type	Name	Description
DRUG	AvidinOX	AvidinOX vial containing 22.5 mg AvidinOX \+ vials containing 10 ml of water for injection (WFI) for the reconstitution in a clear solution with an AvidinOX concentration of 3 mg/ml. One Intralesion administration of a volume of reconstituted AvidinOX equal to about 15 % of the estimated lesion volume
DRUG	177Lu-ST2210	177Lu-ST2210 dose starting at 7.5 Gigabequerel (GBq) ±10%with escalation steps of 2.5 GBq up to 15 GBq ±10%, approximately 1 mg ST2210
DRUG	177Lu-ST2210	Second dose of 177Lu-ST2210 dose (14 days after the first dose) starting at 7.5 Gigabequerel (GBq) ±10%with escalation steps of 2.5 GBq up to 15 GBq ±10%, approximately 1 mg ST2210

Timeline

• Start date: 2017-08-07
• Primary completion: 2019-06-30
• Completion: 2019-07-01
• First posted: 2017-06-15
• Last updated: 2019-07-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study