Tamoxifen for Pancreatic Cysts

(MCN_Tam Trial)

Overseen By Mahdi Hassan, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Nebraska

Must not be taking: Estrogen antagonists, Hormonal treatments

Disqualifiers: Invasive adenocarcinoma, Stroke, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

15 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop using tamoxifen or other estrogen antagonists, as well as certain hormonal treatments like estrogen, progesterone, and androgens. If you are currently using warfarin, you will also need to stop. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug Tamoxifen for pancreatic cysts?

Some studies suggest that Tamoxifen might help extend survival in certain cases of pancreatic cancer, but overall, the evidence does not show a significant benefit for patients with advanced pancreatic cancer. In some trials, Tamoxifen did not improve survival or quality of life compared to a placebo. ^{1 2 3 4 5}

Is tamoxifen generally safe for humans?

Tamoxifen is generally considered safe for humans, but there have been rare reports of it causing pancreatitis (inflammation of the pancreas). ^{1 2 4 6 7}

How is the drug Tamoxifen unique for treating pancreatic cysts?

Tamoxifen is unique for treating pancreatic cysts because it targets estrogen receptors found in pancreatic cancer cells, which is different from most treatments that do not focus on hormone receptors. This approach is based on its use in other cancers, like breast cancer, where it blocks estrogen's effects, potentially slowing tumor growth. ^{1 2 3 5 8}

What is the purpose of this trial?

Pancreatic mucinous cystic neoplasm (MCN) is a precursor to invasive pancreatic adenocarcinoma which occurs almost exclusively in females in their 5th-7th decade. Currently the only option for MCN treatment and prevention of invasive pancreatic ductal adenocarcinoma (PDA) is oncologic resection. The clinical features of pancreatic MCN support the influence of sex hormones in the pathogenesis of the disease. Anti-hormonal therapy may therefore constitute an effective approach to treatment. Preliminary analyses from preclinical studies suggest that tamoxifen inhibits the spread and normal life cycle in MCN epithelial cells and fibroblasts. Investigators hypothesize that in humans, treatment with tamoxifen will lead to cyst regression or stabilization and may spare or delay the need for resection. Up to 15 participants not undergoing immediate resection will be enrolled and take tamoxifen orally for up to 24 weeks. The study will assess the feasibility of tamoxifen as a treatment for pancreatic MCN.

Research Team

Kelsey Klute, MD

Principal Investigator

University of Nebraska

Eligibility Criteria

This trial is for individuals with certain types of non-cancerous pancreatic cysts known as mucinous cystic neoplasms (MCNs) who are not scheduled for immediate surgery to remove these cysts. Specific eligibility details are not provided.

Inclusion Criteria

Willing and able to provide informed consent to and abide by the protocol

Estimated glomerular filtration rate (eGFR) > 30mL/min/1.73m2

My condition is a type of non-invasive pancreatic cyst.

Exclusion Criteria

I have been diagnosed with a serious type of pancreatic cancer or pre-cancer.

I am using or plan to use hormonal treatments, but I can use a levonorgestrel-releasing IUD.

I do not have conditions that prevent me from taking tamoxifen.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tamoxifen 20mg by mouth daily for up to 24 weeks

24 weeks

Regular visits for monitoring and adherence checks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

MRI/MRCP assessments to evaluate response

Treatment Details

Interventions

• Tamoxifen

Trial Overview The study is testing the effectiveness of a medication called Tamoxifen, taken orally at a dose of 20mg daily, in preventing cancer in patients with MCN. Up to 15 participants will be involved and the treatment duration is up to 24 weeks.

Participant Groups

Group I: Tamoxifen Experimental Treatment 1 Intervention

Tamoxifen 20mg by mouth daily for up to 6 months

Tamoxifen is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Nolvadex for:

• Breast cancer
• Infertility
• Gynecomastia

Approved in United States as Tamoxifen citrate for:

• Breast cancer
• Reduction in breast cancer incidence in high-risk women
• McCune-Albright Syndrome

Approved in Canada as Tamoxifen for:

• Breast cancer
• Reduction in breast cancer incidence in high-risk women

Approved in Japan as Tamoxifen for:

• Breast cancer

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Findings from Research

Tamoxifen, an anti-estrogen, has been tested in clinical trials for patients with unresectable pancreatic carcinoma, but its effectiveness as a single agent has shown uncertain results regarding survival benefits compared to untreated controls.

Combination treatments, such as intravenous Onconase with oral tamoxifen, may provide a significant survival advantage for some patients with advanced pancreatic cancer, suggesting that synergistic therapies could be more effective than single-agent treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen in patients with advanced pancreatic adenocarcinoma. Mikulski, S.[2011]

In a study involving 14 patients with unresectable pancreatic adenocarcinoma, treatment with tamoxifen did not show any objective response, indicating a lack of efficacy in this context.

Despite previous suggestions that tamoxifen could increase survival in pancreatic cancer patients, this study's results do not support that claim for endocrine manipulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study to evaluate tamoxifen in pancreatic adenocarcinoma. Crowson, MC., Dorrell, A., Rolfe, EB., et al.[2013]

Tamoxifen has shown promising results in phase II clinical trials for pancreatic cancer, with most trials resulting in at least double the average survival, suggesting its potential as an effective treatment despite its lack of effect in laboratory settings.

Cyproterone, an anti-androgen, inhibits tumor growth in pancreatic cancer, while tamoxifen may also serve as a targeted carrier for other cytotoxic drugs, highlighting the need for further investigation into its mechanisms and applications in human patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormones in chemotherapy for pancreatic cancer, chemoagents or carriers? Siu, TO., Kwan, WB.[2013]

In a randomized placebo-controlled trial involving 44 patients with irresectable adenocarcinoma of the pancreas, tamoxifen did not significantly improve survival compared to placebo.

Quality-of-life assessments also showed no significant differences between patients treated with tamoxifen and those receiving placebo, indicating that tamoxifen does not provide a meaningful benefit for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial of tamoxifen in patients with irresectable pancreatic adenocarcinoma. The Yorkshire Gastrointestinal Tumour Group. Taylor, OM., Benson, EA., McMahon, MJ.[2019]

In a study of 65 patients with resected pancreatic adenocarcinoma, tamoxifen combined with immunochemotherapy significantly improved survival rates compared to those not receiving tamoxifen (p < 0.01).

Tamoxifen showed particularly strong benefits in male patients, with a one-year survival rate of 85.6% for those with carcinoma in the head of the pancreas, compared to only 19.1% in the non-tamoxifen group, highlighting its potential as an effective adjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The beneficial effect of tamoxifen therapy in patients with resected adenocarcinoma of the pancreas. Horimi, T., Takasaki, M., Toki, A., et al.[2013]

Tamoxifen therapy can lead to severe acute pancreatitis, as demonstrated by a case report of a 44-year-old woman who experienced recurrent episodes while on the medication.

Given the risks associated with tamoxifen-induced pancreatitis, clinicians should avoid rechallenging patients with tamoxifen if it is suspected to be the cause of pancreatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe acute pancreatitis due to tamoxifen-induced hypertriglyceridemia with positive rechallenge. Sakhri, J., Ben Salem, C., Harbi, H., et al.[2013]

In a study of 22,005 breast cancer patients, tamoxifen use was not significantly associated with an increased risk of acute pancreatitis (AP), with an adjusted hazard ratio of 0.94, indicating no correlation.

The research found no dose-response relationship between tamoxifen use and AP risk, suggesting that tamoxifen is not a contributing factor to the development of AP in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen use and acute pancreatitis: A population-based cohort study. Hsu, FG., Hsieh, YW., Sheu, MJ., et al.[2019]

In a study involving 11 patients with unresectable pancreatic carcinoma, hormone therapy using tamoxifen showed a mean survival of 235 days in 4 treated patients, compared to only 128 days in 7 control patients.

Two patients receiving tamoxifen had particularly long survival times of 321 and 463 days, suggesting that tamoxifen may be an effective treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hormone therapy using tamoxifen in unresectable carcinoma of the pancreas--preliminary study]. Morita, S., Motohara, T., Ogawa, K., et al.[2013]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Tamoxifen in patients with advanced pancreatic adenocarcinoma. [2011]

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

A phase II study to evaluate tamoxifen in pancreatic adenocarcinoma. [2013]

3. Greece pubmed.ncbi.nlm.nih.gov

Hormones in chemotherapy for pancreatic cancer, chemoagents or carriers? [2013]

4. England pubmed.ncbi.nlm.nih.gov

Clinical trial of tamoxifen in patients with irresectable pancreatic adenocarcinoma. The Yorkshire Gastrointestinal Tumour Group. [2019]

5. Greece pubmed.ncbi.nlm.nih.gov

The beneficial effect of tamoxifen therapy in patients with resected adenocarcinoma of the pancreas. [2013]

6. Italy pubmed.ncbi.nlm.nih.gov

Severe acute pancreatitis due to tamoxifen-induced hypertriglyceridemia with positive rechallenge. [2013]

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

Tamoxifen use and acute pancreatitis: A population-based cohort study. [2019]

8. Japan pubmed.ncbi.nlm.nih.gov

[Hormone therapy using tamoxifen in unresectable carcinoma of the pancreas--preliminary study]. [2013]