Study to Test the Combination of Fulvestrant With Lu-DOTATATE for Advanced Pancreatic Neuroendocrine Tumors

NCT06663072 | Recruiting Phase 1 FDA Drug

• 1 other identifier: IRB24-1395
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, open-label study to assess the safety and preliminary efficacy of Fulvestrant in combination with 177Lu-DOTATATE for advanced pNETs.

Conditions

Metastatic Pancreatic Neuroendocrine Tumor

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  The rates of tumor response categories (CR, PR, SD, PD, Not Evaluated, Too Early) will be summarized and compared to historical control of response to PRRT treatment.

  Through study completion, an average of 2 years

• Safety

  Safety will be measured by the incidence of adverse events and serious adverse events.

  8 months for duration of the treatment (until the post-treatment safety follow-up visit)

Secondary Outcomes (4)

• Progression Free Survival

  Through study completion, an average of 2 years

• Progression Free Survival

  12 months

• Overall Survival

  Through study completion, an average of 2 years

• Overall Survival

  12 months

Study Arms (2)

Safety-Run In

EXPERIMENTAL

Safety and tolerability data of the combination treatment from the first 6 patients who complete at least 28 days of safety follow-up after the first dose of combination treatment. If no significant safety issues are identified the study will proceed to Arm 2 (dose expansion).

Drug: Fulvestrant; Drug: 177Lu-DOTATATE

Dose-Expansion

EXPERIMENTAL

Stage 2 will enroll an additional 13 patients for dose expansion. Fulvestrant and 177Lu-DOTATATE will be given at doses 500 mg IM and 7.4 GBq (200 mCi) IV or 3.7 GBq (100 mCi) IV.

Drug: Fulvestrant; Drug: 177Lu-DOTATATE

Interventions

177Lu-DOTATATE DRUG

Safety-Run In: Starting Dose: 7.4 GBq (200 mCi) IV every 8 weeks for a total of 4 Cycles Dose Expansion:177Lu-DOTATATE7.4 GBq (200 mCi) IV or 3.7 GBq (100 mCi) IV: IV dose every 8 weeks for a total of 4 Cycles.

Dose-Expansion; Safety-Run In

Fulvestrant DRUG

Safety-Run In: Starting Dose: 500 mg IM on Days 1, 15, and 29 of Cycle 1; followed by 500 mg IM on Days 1 and 29 of every cycle thereafter for a total of 9 doses. Dose Expansion: 500 mg IM: Days 1, 15, and 29 of Cycle 1; followed by 500 mg IM on Days 1 and 29 of every cycle thereafter for a total of 9 doses.

Dose-Expansion; Safety-Run In

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed pancreatic neuroendocrine tumor, WHO grades 1-2, Ki-67 index of \<20%.
• Patients must have locally advanced disease that is ineligible for curative-intent resection, or metastatic disease.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam.
• Patients must also have tumors expressing somatostatin receptor, defined as radiotracer avid lesions as assessed by a previous DOTATATE PET scan.
• Patients must have radiographically progressed (as per RECIST v1.1 criteria) on one or more prior-lines of systemic therapy prior to enrollment in the trial. Prior systemic therapies include but are not limited to somatostatin analogs (octreotide LAR, lanreotide), Capecitabine/Temozolomide, tyrosine kinase inhibitors (e.g. everolimus), VEGF pathway inhibitors (e.g. sunitinib, cabozantinib), and/or other systemic chemotherapy.
• Patients should not have received any prior systemic therapy with peptide receptor radionuclide therapy (including 177Lu-DOTATATE) and/or Fulvestrant.
• Prior treatment with hepatic intra-arterial embolic therapies is allowed if there is recovery from all toxicities, measurable lesions do not include embolized liver unless there has been clear subsequent progression, all measurable lesions are somatostatin receptor avid, and treatment completed at least 2 months prior to registration.
• Prior treatment with cryoablation or thermal/radiofrequency ablation of metastases is allowed if there is recovery from all toxicities, measurable lesions do not include treated metastases, and treatment completed at least 2 months prior to registration.
• Concomitant Medication: Concurrent SSA use while on protocol therapy is allowed provided that the patient: 1) has a functional tumor (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome), 2) has been on a stable dose of somatostatin analog therapy for at least three months, and 3) has previously demonstrated radiographic disease progression while on SSA therapy. There should be a minimum of 28 days between long-acting SSA and 177Lu-DOTATATE dosing. Short-acting SSAs should not be administered within 24 hours of 177Lu-DOTATATE dosing. Following lutetium 177Lu-DOTATATE dosing, long-acting SSAs may be administered between 4 and 24 hours after each dose.
• Age ≥18 years. As neuroendocrine tumors are very rare in children, patients \<18 years of age will be excluded from this study. Furthermore, no reliable dosing or adverse event data are currently available on the use of Fulvestrant patients \<18 years of age.
• ECOG performance status of 0 or 1.
• Patients must have adequate organ and marrow function as defined below:
• Absolute Neutrophil Count ≥1,500/µL
• Platelet Count ≥100,000/µL
• Hemoglobin ≥ 9g/dL

You may not qualify if:

• Patients who are unable to provide or understand written informed consent and comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions.
• Patients who are receiving any other investigational agents.
• Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years.
• Pregnant or breastfeeding.
• Clinical or laboratory signs of imminent organ failure, as determined by the treating investigator.
• Patients with known untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

RECRUITING

MeSH Terms

Conditions

Adenoma, Islet Cell

Interventions

Fulvestrant; lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Chih-Yi (Andy) Liao, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Intake

CONTACT

855-702-8222; cancerclinicaltrials@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase I, open-label study to assess the safety and preliminary efficacy of Fulvestrant in combination with 177Lu-DOTATATE for advanced pNETs. It will involve two stages: Stage 1, a safety run-in stage (enrolling 6-12 patients), and Stage 2, a dose-expansion stage (enrolling 13 patients).

Study Record Dates

• First Submitted: October 22, 2024
• First Posted: October 29, 2024
• Study Start: December 13, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: January 9, 2026

Record last verified: 2026-01

Locations

US (1)