Fulvestrant + Lu-DOTATATE for Pancreatic Neuroendocrine Tumors

Overseen By Clinical Trials Intake

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Chicago

Must be taking: Somatostatin analogs

Disqualifiers: Active malignancy, Pregnant, Organ failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

25 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it allows the use of somatostatin analogs (a type of medication) under certain conditions. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Fulvestrant for treating pancreatic neuroendocrine tumors?

Fulvestrant has shown effectiveness in treating advanced breast cancer, particularly in postmenopausal women with hormone receptor-positive tumors, by inhibiting estrogen's effects. While there is no direct evidence for pancreatic neuroendocrine tumors, its success in hormone-sensitive cancers suggests potential benefits. ^{1 2 3 4 5}

Is the combination of Fulvestrant and 177Lu-DOTATATE safe for treating pancreatic neuroendocrine tumors?

177Lu-DOTATATE has been studied for safety in patients with neuroendocrine tumors, showing it is generally well-tolerated. Some patients experienced serious side effects like bone marrow toxicity and kidney issues, but these were rare. Fulvestrant, also known as Faslodex, is generally considered safe, with common side effects including hot flashes and nausea. ^{6 7 8 9 10}

How is the treatment with Fulvestrant and 177Lu-DOTATATE unique for pancreatic neuroendocrine tumors?

This treatment combines Fulvestrant, a drug that blocks estrogen receptors, with 177Lu-DOTATATE, a targeted therapy that delivers radiation directly to tumor cells with specific receptors. This combination is unique because it targets both hormone-driven growth and directly attacks tumor cells, offering a novel approach for patients with pancreatic neuroendocrine tumors. ^{7 11 12 13 14}

What is the purpose of this trial?

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.

Research Team

Chih-Yi (Andy) Liao, MD

Principal Investigator

University of Chicago

Eligibility Criteria

This trial is for adults with advanced pancreatic neuroendocrine tumors (pNETs) who have progressed after standard therapy. Participants must be able to perform daily activities with minimal assistance and have acceptable blood test results.

Inclusion Criteria

I have had treatment for brain metastases.

My tumor has somatostatin receptors.

I had hepatitis C but am now cured or have no detectable virus while on treatment.

Exclusion Criteria

I have brain metastases that have not been treated.

I have another active cancer besides non-melanoma skin cancer.

Patients unable to provide or understand written informed consent and comply with study procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety-Run In

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

4 weeks

1 visit (in-person)

Dose-Expansion

Stage 2 will enroll an additional 13 patients for dose expansion. Fulvestrant and 177Lu-DOTATATE will be given at specified doses

8 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• 177Lu-DOTATATE
• Fulvestrant

Trial Overview The study tests the safety and initial effectiveness of combining Fulvestrant, a hormone therapy, with Lu-DOTATATE, a radioactive drug targeting tumor cells in patients with pNETs. It's an early-stage trial where everyone gets both treatments.

Participant Groups

Group I: Safety-Run In Experimental Treatment 2 Interventions

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).

Group II: Dose-Expansion Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Findings from Research

A patient with advanced breast cancer achieved a complete remission after 9 years of treatment with fulvestrant, despite previous poor responses to other endocrine therapies.

The patient's unique sensitivity to fulvestrant may explain both the remarkable efficacy and the significant mucosal toxicity experienced during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose Fulvestrant Maintained Long-Term Complete Remission after Poor Response to Previous Endocrine Therapies in a Patient with Advanced Breast Cancer. Hawle, H., Hess, D., Mueller, A., et al.[2021]

Fulvestrant is an estrogen receptor downregulator being developed for the treatment of advanced breast cancer in postmenopausal women, with an NDA filed in the US for its use as a second-line therapy.

The drug shows potential not only for breast cancer but also for other estrogen-responsive tumors, such as uterine tumors, although further development for these indications has not been reported since the late 1990s.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (AstraZeneca). Johnston, SR.[2018]

A systematic review of 32 trials involving 12,726 patients found that combining novel targeted inhibitors with fulvestrant or exemestane significantly improves progression-free survival in advanced breast cancer compared to fulvestrant alone, with hazard ratios between 0.62 and 0.82.

The combination of exemestane plus everolimus showed the highest clinical benefit and overall response rates, making it one of the top treatment options for hormone receptor-positive, HER2-negative advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine therapies in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative, pretreated, advanced breast cancer: A network meta-analysis. Lee, CH., Kang, YN., Ho, CL., et al.[2022]

In a study of 69 postmenopausal women with advanced, recurrent ER-positive breast cancer, 500 mg of fulvestrant showed a favorable objective response rate of 24.6% and a clinical benefit rate of 49.2%.

The treatment was generally safe, with mild to moderate adverse effects like injection site reactions and hot flushes, and it was particularly effective in patients without a history of prior treatments or visceral metastasis, with a median overall survival of 794 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of the Selective Estrogen Receptor Down-Regulator "Fulvestrant" in Japanese Patients with Advanced, Recurrent, ER-Positive Postmenopausal Breast Cancer]. Egawa, C., Okishiro, M., Takatsuka, Y.[2022]

Fulvestrant is an effective treatment for postmenopausal women with hormone-sensitive metastatic breast cancer, showing similar response rates to anastrozole in two phase III studies involving 851 participants, with 17-20% response rates for fulvestrant compared to 15-17% for anastrozole.

The most common side effects of fulvestrant include injection-site reactions and hot flashes, with no significant differences in safety profiles between fulvestrant and anastrozole, leading to its FDA approval for patients who have progressed after tamoxifen therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: fulvestrant. Bross, PF., Cohen, MH., Williams, GA., et al.[2019]

In a study of 110 patients with advanced pancreatic neuroendocrine tumors (panNETs), treatment with 177Lu-DOTATATE resulted in a median progression-free survival (PFS) of 24.8 months and an overall survival (OS) of 41.4 months, indicating its efficacy in managing this type of cancer.

The treatment was well-tolerated, with no serious adverse events leading to discontinuation, and only a small percentage of patients experiencing grade 3 side effects, suggesting a favorable safety profile for 177Lu-DOTATATE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of 177Lu‑DOTATATE in patients with advanced pancreatic neuroendocrine tumours: data from the NETTER-R international, retrospective study. Clement, D., Navalkissoor, S., Srirajaskanthan, R., et al.[2022]

177 Lu-DOTATATE significantly improved symptoms and disease control in patients with progressive metastatic functioning neuroendocrine tumors (F-NETs), with 88.1% of patients showing a syndrome response after treatment.

The treatment demonstrated a median progression-free survival of 33.0 months and a 2-year overall survival rate of 87.8%, indicating its efficacy, especially in syndromic responders who had a much higher survival rate compared to non-responders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-DOTATATE Efficacy and Safety in Functioning Neuroendocrine Tumors: A Joint Analysis of Phase II Prospective Clinical Trials. Bongiovanni, A., Nicolini, S., Ibrahim, T., et al.[2022]

In a study of 71 patients aged 70 and older with advanced neuroendocrine tumors treated with 177Lu-DOTATATE, the treatment showed a median progression-free survival of 36 months and overall survival of 47 months, indicating its efficacy in this age group.

The treatment was well-tolerated, with only 2.8% experiencing significant myelosuppression, and there was no decline in health-related quality of life, suggesting that 177Lu-DOTATATE is a safe option for older patients with advanced NET.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-DOTATATE in older patients with metastatic neuroendocrine tumours: safety, efficacy and health-related quality of life. Chen, L., Navalkissoor, S., Quigley, AM., et al.[2021]

177 Lu-DOTATATE therapy has shown to be an effective treatment for advanced metastatic neuroendocrine tumors (NETs), with a median progression-free survival of 33 months and overall survival of 46 months based on a study of 395 patients.

The treatment is generally well-tolerated, with only 8% of patients experiencing severe bone marrow toxicity and a very low incidence of serious nephrotoxicity, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single centre retrospective review of outcome of 177 Lu-DOTATATE peptide receptor radionuclide therapy in the treatment of progressive metastatic neuroendocrine tumours: Survival, toxicity, and prognostic factors. Alsadik, S., Gnanasegaran, G., Chen, L., et al.[2022]

In a phase 1/2 study involving 15 Japanese patients with advanced neuroendocrine tumors, 177 Lu-DOTATATE treatment resulted in a 53% objective response rate, indicating significant tumor shrinkage.

The treatment was well-tolerated, with absorbed radiation doses to the kidneys and bone marrow remaining within safe limits, although some patients experienced Grade 3 adverse events like lymphopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and response after peptide receptor radionuclide therapy with 177 Lu-DOTATATE for neuroendocrine tumors in phase 1/2 prospective Japanese trial. Kudo, A., Tateishi, U., Yoshimura, R., et al.[2022]

Lu-DOTATATE is an effective treatment for inoperable metastatic well-differentiated pancreatic neuroendocrine tumors, even in patients with terminal renal failure, as demonstrated in a case study of a 74-year-old woman.

The patient achieved complete remission 12 months after receiving 4 cycles of Lu-DOTATATE therapy while undergoing hemodialysis, with normal blood parameters maintained at 12 and 30 months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful and Safe Treatment With 177Lu-DOTATATE (Lutathera) of Progressive Metastatic Pancreatic Neuroendocrine Tumor Under Hemodialysis. Dierickx, LO., Séverine, B., Fatima, M., et al.[2021]

Lutetium-177-dotatate (177 Lu-dotatate) is an FDA-approved treatment for advanced somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs), based on positive results from the NETTER-1 trial.

A case study presented shows that a patient with a grade 3 pancreatic neuroendocrine tumor and a BRCA1 germline mutation experienced a significant response to 177 Lu-dotatate, suggesting its potential efficacy even in more aggressive tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Homologous Recombination Repair Defect May Predict Treatment Response to Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors. Zhu, M., Bassam Sonbol, M., Halfdanarson, T., et al.[2022]

In a study of 60 patients with advanced pancreatic neuroendocrine tumors (P-NETs), Lu-DOTATATE (Lu-PRRT) demonstrated a high disease control rate of 85.7% with full activity (FA) and 78.1% with reduced activity (RA), indicating its efficacy as a treatment option.

Patients receiving the higher dose of Lu-PRRT (27.8 GBq) had significantly longer median progression-free survival (53.4 months) and overall survival compared to those receiving the lower dose (18.5 GBq), while FDG PET scans were found to be an important prognostic factor, with FDG PET-negative patients showing much better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with 177Lu-D OTATATE. Sansovini, M., Severi, S., Ianniello, A., et al.[2022]

177 Lu-DOTATATE therapy in 30 patients with neuroendocrine tumors and extensive bone metastases showed a median progression-free survival of 27 months and overall survival of 35 months, indicating its efficacy in this challenging patient population.

The treatment was generally safe, with only 10% experiencing severe bone marrow toxicity and no cases of severe kidney toxicity, while patients reported significant improvements in their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of 177 Lu-DOTATATE in Neuroendocrine Tumor Patients With Extensive Bone Disease. Alsadik, S., Gnanasegaran, G., Chen, L., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Low-Dose Fulvestrant Maintained Long-Term Complete Remission after Poor Response to Previous Endocrine Therapies in a Patient with Advanced Breast Cancer. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Fulvestrant (AstraZeneca). [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Endocrine therapies in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative, pretreated, advanced breast cancer: A network meta-analysis. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of the Selective Estrogen Receptor Down-Regulator "Fulvestrant" in Japanese Patients with Advanced, Recurrent, ER-Positive Postmenopausal Breast Cancer]. [2022]

5. England pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: fulvestrant. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of 177Lu‑DOTATATE in patients with advanced pancreatic neuroendocrine tumours: data from the NETTER-R international, retrospective study. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

177Lu-DOTATATE Efficacy and Safety in Functioning Neuroendocrine Tumors: A Joint Analysis of Phase II Prospective Clinical Trials. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

177Lu-DOTATATE in older patients with metastatic neuroendocrine tumours: safety, efficacy and health-related quality of life. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Single centre retrospective review of outcome of 177 Lu-DOTATATE peptide receptor radionuclide therapy in the treatment of progressive metastatic neuroendocrine tumours: Survival, toxicity, and prognostic factors. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

Safety and response after peptide receptor radionuclide therapy with 177 Lu-DOTATATE for neuroendocrine tumors in phase 1/2 prospective Japanese trial. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Successful and Safe Treatment With 177Lu-DOTATATE (Lutathera) of Progressive Metastatic Pancreatic Neuroendocrine Tumor Under Hemodialysis. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Homologous Recombination Repair Defect May Predict Treatment Response to Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with 177Lu-D OTATATE. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of 177 Lu-DOTATATE in Neuroendocrine Tumor Patients With Extensive Bone Disease. [2023]