Nilotinib + Paclitaxel for Advanced Cancer

Recruiting at 1 trial location

Overseen By DTC Referral Coordinators

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antiretrovirals

Disqualifiers: Active brain metastases, Uncontrolled illness, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 28-day cycles

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding nilotinib, a type of cancer treatment, can enhance the effectiveness of paclitaxel against advanced cancer when standard treatments have failed or are unavailable. Researchers aim to determine the safety of these two drugs together and identify the safest doses. Adults with advanced cancer that has worsened after previous treatments or lacks effective options are suitable candidates for this trial. Participants will take nilotinib orally and receive paclitaxel through an IV in cycles, with regular visits for exams and tests. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on HIV medication or any investigational drugs, you may not be eligible to participate. It's best to discuss your specific medications with the trial team.

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

Research shows that the combination of nilotinib and paclitaxel has been studied for safety in people with advanced cancer. In earlier studies, this combination showed promise, with some patients experiencing partial responses, meaning their tumors shrank somewhat.

Regarding safety, studies found that this combination can be administered safely at certain doses. Patients experienced some side effects, but these were generally manageable. The most common side effects included tiredness and nausea, which are typical with cancer treatments. Participants should inform their doctors about any side effects they experience.

Both nilotinib and paclitaxel have approval for other uses, providing some reassurance about their safety. However, using them together is still under careful testing to ensure safety and effectiveness for treating advanced cancers. Participants should always discuss potential risks and benefits with their healthcare provider before considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Nilotinib and Paclitaxel for advanced cancer because it blends two powerful mechanisms. Nilotinib is known for targeting specific proteins within cancer cells that help them grow, while Paclitaxel disrupts the ability of cancer cells to divide. This combination approach could potentially offer a more comprehensive attack on cancer cells compared to existing treatments that typically focus on a single method. Additionally, Nilotinib's oral administration may offer more convenience compared to some standard treatments that require frequent hospital visits for infusions.

What evidence suggests that nilotinib plus paclitaxel might be an effective treatment for advanced cancer?

This trial examines the combination of nilotinib and paclitaxel for advanced cancer. Studies have shown that using nilotinib with paclitaxel might be more effective than paclitaxel alone. Research with human cancer cells suggests these drugs work better together, potentially enhancing their effectiveness against cancer. In a study involving patients with various rare cancers, some experienced partial tumor shrinkage with this combination, indicating it might help reduce tumors. Nilotinib affects certain proteins that might otherwise hinder paclitaxel, potentially boosting its cancer-fighting ability. This trial aims to determine if this combination can offer better treatment options for advanced cancer. ^{3 4 6 7 8}

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 over 18 with advanced solid tumors that have worsened after standard treatment or where no effective therapy exists. They must be in good enough health, not have had certain treatments recently, and agree to use contraception. Excluded are those with specific heart conditions, uncontrolled illnesses, brain metastases requiring medication, pregnant or breastfeeding women, and those with severe allergies to similar drugs.

Inclusion Criteria

My blood counts and liver/kidney functions are within normal ranges.

Life expectancy of greater than 3 months

I am willing to provide tissue samples for research.

Exclusion Criteria

History of allergic reactions to compounds of similar composition to study drugs

My heart's electrical activity is normal, and I don't have a genetic heart condition.

My nerve damage does not severely affect my daily activities.

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 orally twice daily and paclitaxel intravenously once a week for the first 3 weeks of a 28-day cycle

28-day cycles

Weekly visits for cycle 1, then first 3 weeks of subsequent cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a call 30 days after stopping the study drugs to discuss side effects

4 weeks

1 call (virtual)

Pediatric Expansion

Pediatric patients aged 12-17 are accrued to evaluate the safety, pharmacokinetics, and pharmacodynamics of the drug combination

Ongoing

What Are the Treatments Tested in This Trial?

Interventions

• Nilotinib
• Paclitaxel

Trial Overview The trial is testing the combination of two cancer drugs: Nilotinib taken orally twice daily (except the first day) and Paclitaxel given by IV once a week for three weeks in each cycle. The goal is to see if Nilotinib can make Paclitaxel more effective against cancer. Participants will undergo regular physical exams, blood tests, scans every 8 weeks and keep a medicine diary.

How Is the Trial Designed?

Group I: treatment Experimental Treatment 1 Intervention

The starting dose of nilotinib will be administered at 300 mg orally BID from cycle 1 day 2 and paclitaxel will be administered IV at 60 mg/m2 at dose level 1 on Days 1, 8, and 15 in 28-day cycles. For cycle 2 on, nilotinib will be administered from day 1. Dose escalation will follow a 3+3 design, with dose limiting toxicities defined during cycle 1.

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

A meta-analysis of nine trials with 1190 patients showed that platinum-based chemotherapy provides a survival benefit for patients with advanced non-small cell lung cancer compared to best supportive care.

Recent studies indicate that newer agents like paclitaxel and docetaxel, when combined with platinum-based regimens, offer modest improvements in survival and quality of life, but no single combination has been found superior in terms of survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxic chemotherapy in advanced non-small cell lung cancer: a review of standard treatment paradigms. Socinski, MA.[2015]

A new regimen combining doxorubicin and paclitaxel has been developed that is both well-tolerated and highly effective, utilizing bolus administration of doxorubicin and a 3-hour infusion of paclitaxel, overcoming previous schedule-dependent toxicity issues.

Paclitaxel has shown promising results when combined with fluorouracil and folinic acid in patients with extensive prior chemotherapy, and adding mitoxantrone to this combination appears to enhance its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-based combination chemotherapy for breast cancer. Hortobagyi, GN.[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]

Paclitaxel (Taxol) has shown significant antitumor activity in advanced ovarian and breast cancers, as well as some efficacy in lung cancer, based on results from various phase I and II trials.

The drug works by stabilizing microtubules, leading to mitotic arrest, and can be administered through different infusion durations without losing effectiveness, with shorter infusions potentially reducing the risk of neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a novel anticancer chemotherapeutic drug. Long, HJ.[2019]

A pooled analysis of the ABOUND clinical trial program showed that nab-paclitaxel-based regimens provide median progression-free survival (PFS) of 4.1 months for patients with poor performance status (ECOG PS 2) and up to 7.7 months for patients with diabetes, indicating varying efficacy based on patient comorbidities.

Overall survival (OS) rates were 18.2 months for patients with renal impairment and 16.1 months for elderly patients, but those with ECOG PS 2 had significantly shorter OS at 5.6 months, highlighting the need for careful treatment consideration in vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel/Carboplatin in Vulnerable Populations With Advanced Non-Small Cell Lung Cancer: Pooled Analysis. Langer, CJ., Gajra, A., Gridelli, C., et al.[2022]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

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]

Paclitaxel (Taxol) has a proven safety profile and antitumor activity, leading to its investigation as a single-agent therapy and in combination with other drugs for advanced breast cancer treatment.

Current studies at Memorial Sloan-Kettering Cancer Center are exploring various infusion schedules and combinations of paclitaxel with other agents, including monoclonal antibodies, to enhance efficacy and define safety profiles, particularly in node-positive stage II-III breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel for breast cancer: the Memorial Sloan-Kettering Cancer Center experience. Seidman, AD., Hudis, CA., Raptis, G., et al.[2015]

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]

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, a novel antineoplastic drug, has shown significant effectiveness in treating advanced cancers such as ovarian, breast, non-small cell lung cancer, and head and neck cancer, with a potential to become a first-line treatment when combined with platinum for advanced ovarian cancer.

While initial hypersensitivity reactions posed challenges, current premedication strategies have reduced these side effects to less than 3%, although neutropenia remains a major dose-limiting adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. Hájek, R., Vorlicek, J., Slavik, M.[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]

Citations

1. 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- ...

2. ecog-acrin.org ecog-acrin.org/ecog-acrin-adds-a-new-treatment-trial-to-the-combomatch-precision-medicine-initiative/

New treatment trial added to the ComboMATCH precision ... Pre-clinical studies using human tumor cell lines recently showed that nilotinib and paclitaxel may be stronger and more effective together at ...

3. 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 Ewing ...

4. scientificarchives.com scientificarchives.com/article/repurposing-nilotinib-as-a-selective-p38b-inhibitor-in-hematopoietic-malignancies-clinical-evidence-and-mechanistic-insights

Repurposing Nilotinib as a Selective P38? Inhibitor in ... Clinical and FDA Adverse Event Reporting System (FAERS) data revealed higher toxicity rates for Nilotinib in Ph+ CML and off-target effects in non-CML cancers.

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

Nilotinib + Paclitaxel for Rare Cancers This Phase 2 medical study run by National Cancer Institute (NCI) is evaluating whether Nilotinib and Paclitaxel will have tolerable side effects & efficacy ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40105437/

A phase 1 study of nilotinib in combination with paclitaxel ... This study determined the MTD of this combination, demonstrated sustained cPRs in patients with AOGCT, and profiled molecular ...

7. aacrjournals.org aacrjournals.org/clincancerres/article/31/11/2124/762524/A-Phase-I-Study-of-Nilotinib-in-Combination-with

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

8. asco.org asco.org/abstracts-presentations/ABSTRACT367276

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 ...