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

Trial Summary

What is the purpose of this trial?

Background: People with rare cancers often have limited treatment options. The biology of rare cancers is not well understood. Researchers want to find better treatments for these cancers. They want to test 2 drugs that, taken separately, have helped people with non-rare cancers. They want to see if these drugs together can make rare cancers shrink or stop growing. 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 that has progressed after receiving standard treatment, or for which no effective therapy exists. Design: Participants will be screened with medical history and physical exam. They will have blood and urine tests. They will have a pregnancy test if needed. They will have an electrocardiogram to check their heart. They will have imaging scans to measure their tumors. Participants will repeat the screening tests during the study. Participants will receive nilotinib and paclitaxel. The drugs are given in 28-day cycles. Nilotinib is a capsule taken by mouth twice a day. Paclitaxel will be given intravenously by peripheral line or central line once a week for the first 3 weeks of each cycle. Participants will keep a medicine diary. They will track when they take the study drugs and any side effects they may have. Participants may have optional tumor biopsies. Participants can stay on the study until their disease gets worse or they have intolerable side effects. Participants will have a follow-up phone call about 30 days after taking the last dose of study drugs.

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.

What data supports the effectiveness of the drug Nilotinib + Paclitaxel for rare cancers?

Research shows that paclitaxel, a component of the treatment, has been effective in treating various cancers like pancreatic, lung, and breast cancer. Nab-paclitaxel, a form of paclitaxel, has shown improved tumor-fighting activity and tolerability in these conditions, suggesting potential benefits for rare cancers as well. ^{1 2 3 4 5}

Is the combination of Nilotinib and Paclitaxel generally safe for humans?

Paclitaxel, also known as Taxol, has been used in treating various cancers and is known to cause side effects like hypersensitivity reactions (allergic reactions), myelosuppression (reduced bone marrow activity), and neurotoxicity (nerve damage). While these side effects can be serious, they are generally manageable with proper medical care. ^{6 7 8 9 10}

What makes the drug combination of Nilotinib and Paclitaxel unique for treating rare cancers?

The combination of Nilotinib and Paclitaxel is unique because it pairs a targeted therapy (Nilotinib) with a chemotherapy drug (Paclitaxel), potentially offering a novel approach for rare cancers where standard treatments may not exist. Paclitaxel works by disrupting cell division, while Nilotinib targets specific cancer cell pathways, which might enhance treatment effectiveness. ^{1 7 8 11 12}

Research Team

Alice P Chen, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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.

You are currently taking part in another research study.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

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 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. [2021]

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

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

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

Phase II study of paclitaxel and epirubicin as first-line treatment in patients with metastatic nonsmall cell lung carcinoma. [2019]

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

Paclitaxel (taxol). [2019]

7. United States 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. [2017]

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

[Paclitaxel (taxol): a review of its antitumor activity and toxicity in clinical studies]. [2015]

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

Clinical development of Taxol. [2015]

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

Hypersensitivity reactions from taxol. [2022]

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

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

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

Paclitaxel for ovarian cancer. [2015]