Paclitaxel + Nilotinib for Cancer

Overseen By Andrew M Blakely, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: QT prolonging, CYP3A4 inhibitors

Disqualifiers: Recent surgery, Uncontrolled illness, HIV, 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: 7

Duration: 9-18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of two drugs, orally administered nilotinib and paclitaxel given through an IV and directly into the abdomen, can shrink tumors sufficiently for surgery. It targets individuals with peritoneal carcinomatosis, where cancer has spread to the abdominal lining from other types, such as colon or ovarian cancer. The trial seeks participants who have this condition and have not responded to previous chemotherapy treatments. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop taking your current medications, but you cannot take drugs that prolong the QT interval or strongly inhibit certain liver enzymes. If you're on such medications, you may need to switch to alternatives that don't have these interactions.

Is there any evidence suggesting that the combination of paclitaxel and nilotinib is likely to be safe for humans?

Research has shown that using nilotinib and paclitaxel together is generally safe. A previous study examined the interaction of these two drugs and found they can effectively control disease in some patients, indicating the combination is usually well-tolerated.

Both nilotinib and paclitaxel have FDA approval for other uses, confirming their safety in people. Early tests of their combined use showed they are safe, as they did not cause unexpected or severe side effects.

Participants in past trials managed the combination well, experiencing manageable side effects. This is encouraging for anyone considering joining a study with these treatments. However, as with any medication, risks exist, so consulting a healthcare provider is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of paclitaxel and nilotinib for cancer treatment because it offers a novel approach compared to standard chemotherapy options. Unlike traditional treatments that rely solely on intravenous administration, this combination integrates both intraperitoneal (IP) and intravenous (IV) delivery methods alongside oral nilotinib. This dual delivery system may enhance the drug's reach and effectiveness, particularly in targeting cancer cells within the abdominal cavity. Additionally, nilotinib, primarily used for certain types of leukemia, targets specific cancer cell pathways, potentially improving outcomes when combined with paclitaxel.

What evidence suggests that the combination of paclitaxel and nilotinib could be effective for peritoneal carcinomatosis?

Research has shown that using paclitaxel and nilotinib together might be more effective than using each drug alone. In this trial, participants will receive a combination of intraperitoneal (IP) and intravenous (IV) paclitaxel with oral nilotinib. Studies with human cancer cells suggest that this combination could be more potent against cancer. Paclitaxel is already known to help treat breast cancer at various stages. Early results from clinical trials with this combination have been promising for patients with rare tumors, potentially shrinking tumors enough to allow surgery for those with peritoneal carcinomatosis. ^{2 4 5 6 7}

Who Is on the Research Team?

Andrew M Blakely, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with peritoneal carcinomatosis from certain cancers, not suitable for surgery due to widespread disease. Must have tried at least one chemotherapy without success and be physically able to participate (ECOG <=2). They should have functioning organs and marrow, agree to use contraception if applicable, and not breastfeed during the trial.

Inclusion Criteria

My cancer, which started in the peritoneum and is not mucinous, has been confirmed by pathology.

I cannot have surgery to reduce my tumor, due to extensive spread or involvement.

My cancer's growth can be tracked with specific medical tests.

Exclusion Criteria

I have moderate to severe numbness, tingling, or pain in my hands or feet.

I have had a lot of fluid in my abdomen or more than two fluid removal procedures recently.

I am not taking medication that affects heart rhythm or interferes with certain liver enzymes.

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 bidirectional chemotherapy with intraperitoneal and intravenous paclitaxel and oral nilotinib in 3-week cycles, for 3 or 6 cycles

9-18 weeks

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits every 3 months for 3 years

3 years

Every 3 months (in-person or with local doctor)

Open-label extension (optional)

Participants may continue to receive nilotinib and IV paclitaxel for up to 1 year after initial treatment cycles

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Nilotinib
• Paclitaxel

Trial Overview The study is testing a new treatment combining oral nilotinib with paclitaxel administered intravenously (IV) and directly into the abdomen (IP) in hopes of shrinking tumors enough for surgery. Participants will undergo multiple cycles of this treatment along with regular health assessments including laparoscopies.

How Is the Trial Designed?

Group I: 1/ IP Catheter Placement and Bidirectional Chemotherapy Experimental Treatment 2 Interventions

IP and IV paclitaxel administration with oral nilotinib

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12130796/

A Phase I Study of Nilotinib in Combination with Paclitaxel ... No data from these studies have been reported to date. Notably, a phase 1b study is actively assessing the efficacy of intermittent nilotinib dosing in ...

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. sciencedirect.com sciencedirect.com/science/article/pii/S2468294225000553

Paclitaxel resistance in breast cancer: Current challenges ... Paclitaxel's clinical evidence in breast cancer. PTX effectively manages BC in the neoadjuvant, adjuvant, and metastatic settings [19].

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3015

Phase 2 evaluation of the nilotinib-paclitaxel combination ... Conclusions: Preliminary clinical outcomes for the nilotinib-paclitaxel combination in patients with rare tumors showed encouraging signals of ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8317518/

A Systemic Review and Meta-analysis - PMC Conclusions: Nab-PTX can improve ORR compared with paclitaxel and should be given priority to when aiming to reduce tumor load in breast cancer. Sb-PTX of dose ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3538397/

The High Cost of Cancer Drugs and What We Can Do ... The FDA may continue to grant approvals based on efficacy and safety data, but the availability of cost and quality-of-life analysis sufficient enough to ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.3026

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