FLT PET/CT Imaging for Breast Cancer

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must be taking: Ribociclib, Paclitaxel

Disqualifiers: Pregnancy, Imaging intolerance, Unstable conditions, others

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

Compensation: Varies

Number of Visits: 3

Duration: Cycle 1: 3 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

In this study positron emission tomography (PET/CT) imaging will be used to evaluate proliferative activity in sites of metastatic disease using the investigational radiotracer \[18F\]fluorothymidine (FLT).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug combination used in the FLT PET/CT Imaging for Breast Cancer trial?

Research shows that paclitaxel, a key component of the treatment, has significant antitumor activity and is effective in treating metastatic breast cancer, as demonstrated in clinical trials. Additionally, ribociclib has been reviewed for its efficacy in hormone receptor-positive metastatic breast cancer, supporting its use in this context. ^{1 2 3 4 5}

Is FLT PET/CT Imaging for Breast Cancer safe for humans?

Abraxane, a form of paclitaxel used in cancer treatment, has been studied for safety and shows some side effects like corneal disorders and other toxicities, but it is generally considered safe for use in humans. However, some patients may experience significant side effects, and treatment may need to be adjusted or stopped due to these toxicities. ^{6 7 8 9 10}

How is the drug combination of Paclitaxel and Ribociclib unique for breast cancer treatment?

The combination of Paclitaxel and Ribociclib for breast cancer is unique because it uses advanced PET imaging techniques, like FLT PET/CT, to assess early treatment response, which can help tailor therapy more effectively compared to traditional methods that rely on tumor size changes. ^{2 11 12 13 14}

Research Team

David Mankoff, MD, PHD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults with metastatic breast cancer that tests positive for the Rb protein. They must be able to receive ribociclib and paclitaxel treatment, have at least one tumor outside of liver and bone detectable by standard imaging, and provide informed consent. Pregnant women or those with serious health or psychological issues are excluded.

Inclusion Criteria

My breast cancer has been confirmed by tests and shows Rb protein.

I have breast cancer that has spread to an area other than the liver or bones.

Participants must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific procedures.

Exclusion Criteria

Ineligible for the therapeutic trial UPCC 06115

Inability to tolerate imaging procedures in the opinion of an investigator or treating physician

Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo [18F]FLT PET/CT imaging to evaluate proliferative activity in metastatic disease sites

1 week

3 visits (in-person)

Treatment

Participants receive ribociclib (LEE011) and weekly Paclitaxel therapy

Cycle 1: 3 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• [18F]FLT
• Paclitaxel
• PET/CT
• Ribociclib

Trial Overview The study is testing how well a special type of PET/CT scan using [18F]FLT can show the growth activity in metastatic breast cancer sites. Participants will also be treated with the chemotherapy drug paclitaxel and the targeted therapy ribociclib.

Participant Groups

Group I: FLT PET/CT Experimental Treatment 4 Interventions

All subjects will receive an \[18F\]FLT PET/CT scan.

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

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

Ribociclib, a CDK 4/6 inhibitor, significantly improves median progression-free survival (PFS) in women with HR+/HER2- metastatic breast cancer when used in combination with endocrine therapy, with PFS ranging from 8 to 13 months across three phase III trials.

The treatment is well tolerated, particularly in elderly patients, and while it has some dose-limiting toxicities like neutropenia and QTc prolongation, it maintains health-related quality of life and reduces pain scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib in HR+/HER2- Advanced or Metastatic Breast Cancer Patients. Rascon, K., Flajc, G., De Angelis, C., et al.[2020]

Paclitaxel (Taxol) is a significant new chemotherapy drug for breast cancer, showing promise in both single-agent and combination treatments.

Ongoing research at Memorial Sloan-Kettering Cancer Center aims to optimize the use of paclitaxel in various treatment settings, including metastatic and adjuvant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. Seidman, AD., Hudis, CA., Fennelly, D., et al.[2015]

In a phase II study involving 43 patients with non-small-cell lung cancer, Abraxane (260 mg/m2) demonstrated a 16% overall response rate and a 49% disease control rate, indicating its efficacy as a first-line therapy.

Abraxane was well tolerated, with no severe hypersensitivity reactions reported and only 5% of patients discontinuing treatment due to mild toxicities, suggesting a favorable safety profile for this novel formulation of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Green, MR., Manikhas, GM., Orlov, S., et al.[2022]

A 55-year-old woman developed corneal disorders, including blurred vision and epithelial defects, after treatment with nab-paclitaxel, indicating that this microtubule inhibitor can cause significant ocular side effects.

After discontinuing nab-paclitaxel, her corneal condition improved dramatically, suggesting that the drug was the likely cause of her symptoms, although the potential contribution of other medications like trastuzumab and pertuzumab should also be considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A Case of a Corneal Disorder after Breast Cancer Treatment with Nab-paclitaxel]. Hosotani, Y., Morimatsu, T., Takata, M., et al.[2016]

In a study of 33 patients with progressive or recurrent non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, Abraxane showed a partial response rate of 33.3%, with better outcomes in patients with squamous cell carcinoma (41.7% response) compared to those with adenocarcinoma (21.1%).

The treatment demonstrated a disease control rate of 75.8% and a median progression-free survival of five months, with manageable side effects, indicating that Abraxane is a potentially effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Abraxane in treatment of progressive and recurrent non-small cell lung cancer patients: A retrospective clinical study. Yuan, DM., Lv, YL., Yao, YW., et al.[2019]

Paclitaxel (TAXOL) therapy presents unique challenges and side effects that require careful management by healthcare professionals, particularly nurses, to ensure patient safety and treatment success.

The review emphasizes the importance of a collaborative nursing plan that identifies specific toxicities associated with paclitaxel and outlines interventions to mitigate these side effects during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing considerations in paclitaxel (Taxol) administration. Lubejko, BG., Sartorius, SE.[2015]

References

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

Ribociclib in HR+/HER2- Advanced or Metastatic Breast Cancer Patients. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

[89Zr]-Pertuzumab PET Imaging Reveals Paclitaxel Treatment Efficacy Is Positively Correlated with HER2 Expression in Human Breast Cancer Xenograft Mouse Models. [2022]

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

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. [2015]

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

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer: from advanced disease to adjuvant therapy. [2015]

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

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

[A Case of a Corneal Disorder after Breast Cancer Treatment with Nab-paclitaxel]. [2016]

7. Singapore pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Abraxane in treatment of progressive and recurrent non-small cell lung cancer patients: A retrospective clinical study. [2019]

8. China pubmed.ncbi.nlm.nih.gov

[Study of bioequiavailability of paclitaxel for Injection (Albumin Bound) and abraxane and the efficacy of extension treatments in patients with metastatic breast cancer]. [2018]

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

Nursing considerations in paclitaxel (Taxol) administration. [2015]

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

Induction of oxidative stress by Taxol® vehicle Cremophor-EL triggers production of interleukin-8 by peripheral blood mononuclear cells through the mechanism not requiring de novo synthesis of mRNA. [2022]

11. China pubmed.ncbi.nlm.nih.gov

Assessment of tumor response to chemotherapy in patients with breast cancer using (18)F-FLT: a meta-analysis. [2020]

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

18F-fluorodeoxyglucose (FDG) PET or 18F-fluorothymidine (FLT) PET to assess early response to aromatase inhibitors (AI) in women with ER+ operable breast cancer in a window-of-opportunity study. [2022]

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

[18F]-3'Deoxy-3'-fluorothymidine positron emission tomography and breast cancer response to docetaxel. [2021]

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

[18F]FDG and [18F]FLT PET for the evaluation of response to neo-adjuvant chemotherapy in a model of triple negative breast cancer. [2018]