NCT05249114

Study of Cabozantinib With Lu-177 in Patients With Somatostatin Receptor 2 Positive Neuroendocrine Tumors

Phase Ib Study of Cabozantinib in Combination With Lu-177 DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) in Patients With Progressive, Previously Treated Somatostatin Receptor 2 (SSTR2) Positive Neuroendocrine Tumors (NETs)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: Providence Health & Services · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The phase I objective of this study is to establish the maximal tolerated dose (MTD) of cabozantinib in 20 mg, 40 mg and 60 mg dose escalation cohorts in combination with Lu-177 dotatate at a standard dose of 7.4 GBq in four (4) 8-week cycles followed by continuation cabozantinib.

Detailed description

Patients will be treated four (4) cycles of combination cabozantinib with Lu-177 DOTATATE followed by maintenance cabozantinib. Cycles 1-4 combination cabozantinib with Lu-177 DOTATATE is given in 8-week cycles, with cabozantinib initiated on day 1 and Lu-177 DOTATATE given on day 14. Cabozantinib dosing is escalated during cycles 1-4 in the following manner: dose cohort 1 patients receive cabozantinib 20 mg daily, cohort 2 receive 40mg qod alternating with 20 mg qod, cohort 3 receive 40 mg qd, dose cohort 4 receive 60 mg qod alternating with 40 mg qod, and dose cohort 5 receive 60 mg qd. In all cohorts, during cycle 5 and beyond, single-agent maintenance cabozantinib is given in 4-week cycles in a qd dosing scheduling as follows: 20 mg qd cohort 1; 40 mg qd cohort 2; 40 mg qd cohort 3; 60 mg qd cohort 4; 60 mg qd cohort 5, until disease progression.

Conditions

• Neuroendocrine Tumors

Interventions

Type	Name	Description
DRUG	Cabozantinib	Cabozantinib tablets are supplied as film coated tablets containing cabozantinib malate equivalent to 20 mg and 60 mg of cabozantinib and contain microcrystalline cellulose, lactose anhydrous, hydoxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate and Opadry yellow. The 60 mg tablets are oval and the 20 mg tablets are round. Doses of 40 mg will comprise two 20-mg tablets.
DRUG	Lu-177	Currently, the only FDA-approved PRRT consists of dotatate, a somatostatin analogue, radiolabeled with Lutetium-177 (Lu177), a beta-minus emitter (brand name Lutathera). Lu177 induces cell death via DNA strand breaks, caspase-3 apoptosis, and interfering with DNA-PK expression (which is associated with DNA repair). PRRT with Lu-177 DOTATATE is a targeted, intravenous therapy inducing DNA damage by delivering ionizing radiation to somatostatin receptor positive tumors.

Timeline

• Start date: 2022-12-28
• Primary completion: 2027-12-01
• Completion: 2029-12-01
• First posted: 2022-02-21
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study