Nilotinib + Paclitaxel for Cancer

Recruiting at 145 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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II ComboMATCH treatment trial evaluates nilotinib with paclitaxel for the treatment of patients with solid cancers that are growing, spreading, or getting worse (progressive) and that have previously been treated with taxane therapies. Nilotinib is in a class of medications called kinase inhibitors. It works by binding to and blocking the action of a protein called ABL, which signals tumor cells to multiply. This helps slow or stop the proliferation of tumor cells. Paclitaxel is a drug that blocks cell growth by stopping cell division and it may kill tumor cells. Giving nilotinib with paclitaxel may be effective at treating patients with progressive solid cancers that have previously been treated with taxane therapies.

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.

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

Paclitaxel has shown significant antitumor activity in various cancers like ovarian, breast, lung, and head and neck cancers, and is often used in combination with other cancer drugs to enhance effectiveness. While specific data on the combination with Nilotinib is not provided, Paclitaxel's proven effectiveness in combination therapies suggests potential benefits. ^{1 2 3 4 5}

What is the safety profile of Paclitaxel (Taxol) in humans?

Paclitaxel (Taxol) has been shown to cause side effects like low white blood cell counts (neutropenia), allergic reactions, nerve damage (peripheral neuropathy), and hair loss. These effects are often related to the dose and schedule of administration, but severe allergic reactions can be managed with premedication. Other side effects include muscle and joint pain, mouth sores, and mild nausea. ^{6 7 8 9 10}

What makes the drug combination of Nilotinib and Paclitaxel unique for cancer treatment?

The combination of Nilotinib and Paclitaxel is unique because it pairs Nilotinib, a drug typically used for chronic myeloid leukemia, with Paclitaxel, a well-known chemotherapy drug that works by stabilizing microtubules to prevent cancer cell division. This novel combination may offer a new approach to treating cancers that have not responded well to standard treatments. ^{1 2 3 11 12}

Research Team

Sarah Shin

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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 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 (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]

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]

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]

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]

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]

References

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

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

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

Analysis of exposure times and dose escalation of paclitaxel in ovarian cancer cell lines. [2019]

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

Paclitaxel for ovarian cancer. [2015]

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

Paclitaxel combination therapy in the treatment of metastatic breast cancer: a review. [2015]

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

Clinical pharmacology of Taxol. [2015]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Paclitaxel via 1-hour infusion: rationale and pharmacology. [2015]

8. Singapore 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. [2019]

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

Paclitaxel (taxol). [2019]

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

Overview of Taxol safety. [2015]

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

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

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

Three-hour paclitaxel infusion in patients with refractory and relapsed non-Hodgkin's lymphoma. [2017]