Nilotinib + Paclitaxel for Rare Cancers

Overseen By Mary Jane Ong

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Nilotinib, Paclitaxel

Must not be taking: Investigational agents

Disqualifiers: CNS malignancy, Long QT syndrome, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 12 months

82 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if two drugs, nilotinib and paclitaxel, can treat rare cancers with limited treatment options. Researchers seek to discover whether these drugs, successful in other cancer types, can shrink or halt the growth of rare tumors. Suitable candidates for this trial have rare, advanced cancers that have worsened after standard treatments or lack effective treatment options. Participants will take nilotinib as a pill twice daily and receive paclitaxel through an IV once a week for three weeks in a four-week cycle. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you must be at least 3 weeks past any major surgery or radiation therapy and at least 5 half-lives or 3 weeks past any chemotherapy or biologic therapy before starting the trial. It's best to discuss your current medications with the trial team to get specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of nilotinib and paclitaxel is generally safe for patients. In one study, only 14.3% of participants experienced a partial response, and serious blood-related side effects were rare. Another study confirmed the safety of this drug combination, noting low rates of serious side effects.

Both nilotinib and paclitaxel have FDA approval for other types of cancer, indicating their prior use and safety for treating other conditions.

Overall, the combination is well-tolerated. While side effects can occur, they are usually manageable. Participants should monitor any side effects and report them to the research team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using nilotinib and paclitaxel for rare cancers because this combination targets cancer cells in a unique way. Nilotinib is a tyrosine kinase inhibitor, which means it blocks specific proteins that cancer cells need to grow, while paclitaxel disrupts the normal process of cell division. This dual approach can potentially be more effective than standard chemotherapy alone, which often focuses solely on stopping cell division. By combining these two treatments, the hope is to enhance their cancer-fighting effects, offering new hope for patients with rare cancers who have limited options.

What evidence suggests that nilotinib and paclitaxel might be effective treatments for rare cancers?

Research has shown that combining nilotinib and paclitaxel may help treat rare cancers. In a study with 30 patients, 7% experienced partial tumor shrinkage. Nilotinib targets specific cancer cell pathways, potentially enhancing the effectiveness of paclitaxel, a drug that inhibits cell division. Participants in this trial will receive this promising combination, which has shown potential in patients with various rare cancers. These findings suggest that using these drugs together might help shrink or halt the growth of rare cancers. ^{1 2 3 5 6}

Who Is on the Research Team?

Alice P Chen, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults aged 18+ with rare, advanced cancers that have worsened after standard treatment or for which no effective therapy exists. Participants must be in good health otherwise, with proper organ and marrow function, and not pregnant or breastfeeding. They should agree to use contraception during the trial and for some time after.

Inclusion Criteria

My cancer is a type of penile cancer known as squamous cell carcinoma.

I have a tumor in my salivary gland.

I have peritoneal mesothelioma.

Exclusion Criteria

I have never had bleeding in my brain or spinal cord.

My cancer has not spread to specific parts of my brain.

I haven't had brain surgery or a brain biopsy in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive nilotinib and paclitaxel in 28-day cycles. Nilotinib is taken orally twice a day, and paclitaxel is administered intravenously once a week for the first 3 weeks of each cycle.

12 months

Weekly visits for paclitaxel administration

Follow-up

Participants are monitored for safety and effectiveness after treatment. A follow-up phone call is conducted about 30 days after the last dose of study drugs.

4 weeks

1 follow-up phone call

What Are the Treatments Tested in This Trial?

Interventions

• Nilotinib
• Paclitaxel

Trial Overview The trial is testing a combination of two drugs—Nilotinib (oral capsule) and Paclitaxel (IV infusion)—to see if they can shrink or halt the growth of rare cancers. The drugs are given in cycles lasting 28 days, with close monitoring through tests and scans.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 1 Intervention

Nilotinib will be administered at 300 mg orally BID; Paclitaxel will be administered IV at 80 mg/m2 on Days 1, 8, and 15 in 28-day cycles.

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

Approved in European Union as Tasigna for:

• Chronic myeloid leukemia (CML) in adult patients resistant to or intolerant of at least one prior therapy including imatinib

Approved in United States as Tasigna for:

• Chronic phase (CP) and accelerated phase (AP) Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in adult patients resistant to or intolerant to prior therapy that included imatinib

Approved in Canada as Tasigna for:

• Chronic myeloid leukemia (CML) in adult patients resistant to or intolerant of at least one prior therapy including imatinib

Approved in Japan as Tasigna for:

• Chronic myeloid leukemia (CML) in adult patients resistant to or intolerant of at least one prior therapy including imatinib

Approved in Switzerland as Tasigna for:

• Chronic myeloid leukemia (CML) in adult patients resistant to or intolerant of at least one prior therapy including imatinib

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Nab-paclitaxel (Abraxane) has been approved as a first-line treatment for advanced non-small-cell lung cancer (NSCLC) due to its improved antitumor activity and better tolerability compared to traditional solvent-based paclitaxel combined with carboplatin.

Taxanes, including nab-paclitaxel, continue to be a crucial part of the standard care for advanced NSCLC, highlighting their favorable risk-benefit profiles in treating this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on taxanes in the first-line treatment of advanced non-small-cell lung cancer. Socinski, MA.[2021]

Paclitaxel demonstrated a 22% objective response rate in women with platinum-refractory ovarian cancer, indicating it can be an effective treatment option for this challenging condition.

While the treatment had an acceptable safety profile, with leukopenia being the most common severe toxicity (78% of patients), there were also treatment-related deaths (1.5%), highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel for platinum-refractory ovarian cancer: results from the first 1,000 patients registered to National Cancer Institute Treatment Referral Center 9103. Trimble, EL., Adams, JD., Vena, D., et al.[2017]

In a study of 301 patients treated with Taxol, 32 experienced hypersensitivity reactions, primarily after their first or second dose, indicating a significant risk of these reactions with early exposure.

Despite premedication in 41% of patients, hypersensitivity reactions still occurred, suggesting that current preventive measures may not be fully effective, and the exact cause of these reactions remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypersensitivity reactions from taxol. Weiss, RB., Donehower, RC., Wiernik, PH., et al.[2022]

Ongoing Phase III trials are exploring the effectiveness of paclitaxel in treating various cancers, including ovarian, breast, lung, and head and neck cancers, indicating its potential as a front-line and adjuvant therapy.

Recent studies have also identified paclitaxel's activity in additional cancer types such as esophageal, bladder, and endometrial cancers, suggesting its broad applicability and encouraging further research into its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel: current developmental approaches of the National Cancer Institute. Arbuck, SG.[2015]

Paclitaxel is an effective treatment for treatment-refractory ovarian cancer, working by stabilizing microtubules to induce cytotoxicity, despite facing challenges like severe hypersensitivity reactions and formulation issues.

The drug is associated with significant side effects, including myelosuppression, mucositis, and neurotoxicity, which are dose-dependent, highlighting the need for careful management in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (taxol). Kohler, DR., Goldspiel, BR.[2019]

Nab-paclitaxel (Abraxane(®)) has been approved by the FDA for treating breast cancer after chemotherapy failure, showing superior efficacy compared to traditional paclitaxel (Taxol(®)).

This new formulation not only demonstrates better effectiveness but also has less toxicity, which enhances its safety profile and therapeutic index, making it a promising option for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. Montero, AJ., Adams, B., Diaz-Montero, CM., et al.[2021]

In a Phase II study involving 32 chemotherapy-naive patients with metastatic non-small cell lung carcinoma (NSCLC), the combination of paclitaxel and epirubicin resulted in a 50% overall response rate, indicating significant efficacy in this patient population.

While the treatment was generally well tolerated, 69% of patients experienced severe neutropenia, which was manageable with G-CSF, and there were concerns about cardiac safety, as one patient died from a ventricular arrhythmia shortly after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of paclitaxel and epirubicin as first-line treatment in patients with metastatic nonsmall cell lung carcinoma. Ceresoli, GL., Dell'Oro, S., Passoni, P., et al.[2019]

Paclitaxel is a cytotoxic drug that belongs to the taxane group and is specifically approved for treating metastatic ovarian carcinoma after standard platinum-based therapies have not been effective.

It represents a new treatment option for patients with advanced ovarian cancer, providing an alternative when traditional therapies fail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel for ovarian cancer. [2015]

Combination therapies using paclitaxel with non-anthracycline agents have shown promising response rates between 40% to 80% and median time to progression exceeding 6 months in phase II and III studies.

Further research through prospective, randomized phase III trials is needed to confirm the benefits of these combinations over older treatments, particularly regarding quality of life, response rates, and survival in metastatic breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus nonanthracycline combinations in metastatic breast cancer. Perez, EA.[2015]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

Paclitaxel is an effective anti-tumor agent that works by stabilizing microtubules, showing significant activity against advanced cancers such as ovarian, lung, breast, and head and neck cancers, especially when combined with cisplatin for ovarian cancer.

While paclitaxel is a key treatment option, it can cause major side effects like hypersensitivity reactions, neutropenia, and peripheral neuropathy, and its combination with other drugs may lead to increased toxicities, indicating the need for careful management in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Paclitaxel (taxol): a review of its antitumor activity and toxicity in clinical studies]. Yamazaki, S., Sekine, I., Saijo, N.[2015]

Taxol, the first drug in the taxane class, effectively stabilizes microtubules and has shown clinical efficacy in treating ovarian, breast, non-small-cell lung, and head and neck cancers, with FDA approval for second-line therapy in ovarian cancer since 1992.

While early studies showed low response rates in other cancers like melanoma and prostate cancer, ongoing evaluations with higher doses or different schedules may improve outcomes, highlighting the need for further research on optimal dosing and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of Taxol. Arbuck, SG., Christian, MC., Fisherman, JS., et al.[2015]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3015

Phase 2 evaluation of the nilotinib-paclitaxel combination ... Results: This study enrolled 31 pts of diverse rare cancers as of the data cut-off. Of the 30 evaluable pts, 2 (7%) had confirmed PRs: 1 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12130796/

A Phase I Study of Nilotinib in Combination with Paclitaxel ... In this study, we present phase 1 clinical safety, response, pharmacokinetic, and pharmacodynamic data for the combination of two such FDA-approved small- ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-04956

RARE 1 Nilotinib and Paclitaxel - NCI Objective: To learn if nilotinib and paclitaxel will benefit people with rare cancers. Eligibility: People age 18 and older who have a rare, advanced cancer ...

4. withpower.com withpower.com/trial/phase-3-7-2020-208d3

Nilotinib + Paclitaxel for Rare Cancers Paclitaxel works by disrupting cell division, while Nilotinib targets specific cancer cell pathways, which might enhance treatment effectiveness. Show more.

5. blog-ecog-acrin.org blog-ecog-acrin.org/combomatch-sparks-progress-an-update-on-the-precision-medicine-initiative/

ComboMATCH Sparks Progress: An Update on the Precision ... E4 is evaluating the activity of nilotinib-paclitaxel in patients with solid tumors who have been treated previously with taxanes. EAY191-A3 and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8189105/

The emerging landscape of immune checkpoint inhibitor ... The objective response rate (ORR) for the entire cohort was 25%, and the 6-month progression-free survival (PFS) was 31%, with a median overall ...