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

Trial Summary

What is the purpose of this trial?

Background: - Researchers want to find better ways to treat cancer. One drug that treats cancer is paclitaxel. Sometimes proteins block that drug from working. Researchers want to see if another drug, nilotinib, helps paclitaxel work better. Objective: - To test the safety of nilotinib plus paclitaxel and find out what doses of the drugs can be given safely to people. Eligibility: - Adults at least 18 years old with advanced cancer that has progressed after receiving standard treatment, or for which no effective therapy exists. Design: * Participants will be screened with tests they usually get in their cancer care: medical history, physical exam, blood and urine tests, heart test, and scans. * Participants will take the two study drugs in 28-day cycles. They will keep a medicine diary. * Nilotinib will be taken by mouth twice every day except day 1 of the first cycle. * Paclitaxel will be given by IV once a week for the first 3 weeks of a cycle. This will usually be done at the clinic. * Most participants will have a weekly study visit every week for cycle 1, then the first 3 weeks of other cycles. They will have: * Physical exam at every visit. * Blood tests multiple times for cycle 1, then the first 3 weeks of other cycles. * Scans every 8 weeks. These may be CT or MRI scans, in a machine that takes pictures. Or they may be ultrasounds, where a wand is pressed on the skin with gel on it. * Around 30 days after stopping the study drugs, participants will be called to discuss any side effects.

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.

What data supports the effectiveness of the drug combination Nilotinib and Paclitaxel for advanced cancer?

Paclitaxel has shown significant activity in treating advanced cancers in various organs, including the ovary, lung, and breast, and is a key component in standard treatments for these cancers. It is often used in combination with other drugs, like cisplatin, to improve outcomes in advanced cancer cases. ^{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, low white blood cell counts (neutropenia), and nerve damage (neurotoxicity). These side effects can be managed with premedication and careful dosing. ^{1 6 7 8 9}

How is the drug combination of Nilotinib and Paclitaxel unique for treating advanced cancer?

The combination of Nilotinib and Paclitaxel is unique because it pairs a targeted therapy (Nilotinib, which is typically used for certain types of leukemia) with a chemotherapy drug (Paclitaxel, known for its effectiveness in various solid tumors), potentially offering a novel approach for advanced cancers that may not respond well to standard treatments. ^{1 5 10 11 12}

Research Team

Alice P Chen, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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, 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]

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]

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]

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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

4. Germany pubmed.ncbi.nlm.nih.gov

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

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

Treatment of ovarian cancer: current status. [2015]

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

Paclitaxel (taxol). [2019]

7. Slovakia pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. [2015]

8. England pubmed.ncbi.nlm.nih.gov

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel/Carboplatin in Vulnerable Populations With Advanced Non-Small Cell Lung Cancer: Pooled Analysis. [2022]

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

Paclitaxel for breast cancer: the Memorial Sloan-Kettering Cancer Center experience. [2015]

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

Paclitaxel-based combination chemotherapy for breast cancer. [2015]

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

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