Nilotinib + Paclitaxel for Cancer

Not currently recruiting at 146 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Platinum-resistant ovarian cancer, Neuropathy, 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: 3

Duration: 28-day cycles, repeated

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of two drugs, nilotinib (a type of targeted therapy) and paclitaxel, to determine their effectiveness in treating solid cancers that have worsened despite previous treatments. Nilotinib blocks a protein that promotes tumor growth, while paclitaxel prevents cancer cells from dividing. The trial targets patients with progressive solid cancers who have previously received taxane therapies. Participants must be willing to undergo blood tests and a tumor biopsy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering patients a chance to contribute to significant advancements in cancer therapy.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, you must have completed any prior therapy at least 4 weeks or 5 half-lives of the prior agent (whichever is shorter) before enrolling in the trial.

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 has been studied for safety. In earlier studies, this combination effectively controlled cancer growth in some patients, successfully managing the disease for certain individuals. The research also indicates that most people can tolerate the treatment well.

One study examined whether nilotinib could prevent paclitaxel's common side effect of nerve damage, highlighting efforts to reduce unwanted effects.

Both nilotinib and paclitaxel have FDA approval for other uses, indicating they have been tested for safety in different conditions. This combination is now under further study, but past findings suggest a positive outlook on safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of nilotinib and paclitaxel because it offers a new approach to treating cancer by combining a targeted therapy with a chemotherapy agent. Nilotinib, originally used in the treatment of chronic myeloid leukemia, targets specific proteins that cancer cells rely on to grow. This makes it potentially more precise in attacking cancer cells compared to standard chemotherapy options that can affect both healthy and cancerous cells. When paired with paclitaxel, a well-established chemotherapy drug that prevents cancer cells from dividing, this combination may enhance overall effectiveness while aiming to minimize side effects.

What evidence suggests that this treatment might be an effective treatment for progressive solid cancers?

Research suggests that combining nilotinib with paclitaxel might help treat certain solid cancers. Early studies show that these drugs can work more effectively together against cancer cells than when used separately. In this trial, participants will receive both nilotinib and paclitaxel. A study with 30 patients who had rare cancers found that 7% responded positively, indicating some promise for this combination. Nilotinib blocks a protein that aids cancer cell growth, while paclitaxel prevents cell division. Together, they might slow down or stop cancer growth. ^{1 3 4 6 7}

Who Is on the Research Team?

Sarah Shin

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Adults with progressive solid cancers previously treated with taxane therapies may join this trial. They must have a safe-to-biopsy tumor or recent tissue sample, no severe peripheral neuropathy, normal heart rhythm (QTcF <= 450 msec), and an ECOG performance status of 0-2. Pregnant or breastfeeding individuals are excluded, as well as those unwilling to use contraception.

Inclusion Criteria

Patient must not have peripheral neuropathy > grade 1

Patient must have documented QT interval with Fridericia's correction (QTcF) of =< 450 msec within 8 days prior to EAY191-E4 registration. Patients with a QTcF interval of >= 450 msec at registration or patients with congenital long QT syndrome are not eligible

Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-E4 based on the presence of an actionable mutation as defined in EAY191

Exclusion Criteria

Patient must not have any of the following mutations (as determined by the ComboMATCH registration protocol), which are known to confer sensitivity or resistance to nilotinib monotherapy: KIT: W557R, V559D, V559A, L576P, and K642E, PDGFR-alpha: D842V

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nilotinib orally twice daily and paclitaxel intravenously on days 1, 8, and 15 of each 28-day cycle

28-day cycles, repeated

3 visits per cycle (in-person)

Follow-up

Participants are monitored for disease progression and survival for up to 3 years

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Nilotinib Hydrochloride Monohydrate
• Paclitaxel

Trial Overview

The trial is testing the combination of nilotinib and paclitaxel in patients whose solid tumors continued to grow after taxane treatment. Nilotinib blocks signals that tell cancer cells to multiply, while paclitaxel stops cell division.

How Is the Trial Designed?

Group I: Treatment (nilotinib hydrochloride monohydrate, paclitaxel) Experimental Treatment 6 Interventions

Patients receive nilotinib hydrochloride monohydrate PO BID on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI throughout the study. Patients also undergo collection of blood samples and tumor biopsy on study.

Nilotinib Hydrochloride Monohydrate 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)
• Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)

Approved in United States as Tasigna for:

• Chronic myeloid leukemia (CML)
• Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)

Approved in Canada as Tasigna for:

• Chronic myeloid leukemia (CML)
• Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)

Approved in Japan as Tasigna for:

• Chronic myeloid leukemia (CML)
• Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)

Approved in Switzerland as Tasigna for:

• Chronic myeloid leukemia (CML)
• Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)

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

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]

Taxol, when administered intravenously, has a well-established safety profile based on data from 655 patients, with myelosuppression, particularly neutropenia, identified as the main dose-limiting toxicity, which was less severe with a 3-hour infusion schedule.

Severe hypersensitivity reactions were effectively managed with a premedication regimen, and while mild to moderate peripheral neuropathy was observed, it rarely led to treatment discontinuation, indicating a generally manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of Taxol safety. Onetto, N., Canetta, R., Winograd, B., et al.[2015]

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 (Taxol) is an effective chemotherapy agent for treating ovarian cancer and metastatic breast cancer, particularly in patients who have not responded to platinum-based treatments.

Nurses must be aware of the potential side effects of Paclitaxel, such as hypersensitivity reactions and peripheral neuropathy, and follow specific administration guidelines to avoid complications related to its interaction with PVC intravenous-giving sets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol)--a guide to administration. Preston, NJ.[2019]

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]

In a study of 60 patients with relapsed non-Hodgkin's lymphoma (NHL), 23% achieved either a partial or complete remission after receiving a 3-hour infusion of 200 mg/m2 of Paclitaxel (Taxol) every 3 weeks, indicating its efficacy as a treatment option.

The treatment was well-tolerated with no allergic reactions or cardiac toxicity reported, although common side effects included hair loss (100%), peripheral neuropathy (37%), and myalgia (25%), suggesting that Taxol can be safely administered in an outpatient setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-hour paclitaxel infusion in patients with refractory and relapsed non-Hodgkin's lymphoma. Younes, A., Sarris, A., Melnyk, A., et al.[2017]

Combination therapies using paclitaxel with other antineoplastic agents show promise for treating metastatic breast cancer, but optimal dosing and scheduling remain unclear, which complicates their development.

Unexpected toxic interactions between paclitaxel and other drugs have been observed, highlighting the need for careful evaluation of combination therapies in clinical trials before they are used outside of research settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel combination therapy in the treatment of metastatic breast cancer: a review. Holmes, FA.[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]

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]

Citations

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Notably, a phase 1b study is actively assessing the efficacy of intermittent nilotinib dosing in attenuating PIPN in patients with breast cancer (NCT04205903), ...

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Pre-clinical studies using human tumor cell lines recently showed that nilotinib and paclitaxel may be stronger and more effective together at ...

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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 Ewing ...

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The combination of nilotinib and paclitaxel demonstrates promising disease control with durable response in select patients.

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Safety, pharmacodynamic, and clinical response ...

Conclusions: The combination of nilotinib and paclitaxel demonstrates promising disease control with durable response in select patients. Tumor PD analyses to ...