Recruiting

Phase 2

Nilotinib & PaclitaxelRapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors (RARE CANCER) Trial: RARE 1 Nilotinib and Paclitaxel

Sponsor:

National Cancer Institute (NCI)

Code:

NCT04449549

Conditions

Neoplasms

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Nilotinib and Paclitaxel

Study Details

Brief summary:

Background:

People with rare cancers often have limited treatment options. The biology of rare cancers is not well understood. Researchers want to find better treatments for these cancers. They want to test 2 drugs that, taken separately, have helped people with non-rare cancers. They want to see if these drugs together can make rare cancers shrink or stop growing.

Objective:

To learn if nilotinib and paclitaxel will benefit people with rare cancers.

Eligibility:

People age 18 and older who have a rare, advanced cancer that has progressed after receiving standard treatment, or for which no effective therapy exists.

Design:

Participants will be screened with medical history and physical exam. They will have blood and urine tests. They will have a pregnancy test if needed. They will have an electrocardiogram to check their heart. They will have imaging scans to measure their tumors.

Participants will repeat the screening tests during the study.

Participants will receive nilotinib and paclitaxel. The drugs are given in 28-day cycles. Nilotinib is a capsule taken by mouth twice a day. Paclitaxel will be given intravenously by peripheral line or central line once a week for the first 3 weeks of each cycle.

Participants will keep a medicine diary. They will track when they take the study drugs and any side effects they may have.

Participants may have optional tumor biopsies.

Participants can stay on the study until their disease gets worse or they have intolerable side effects.

Participants will have a follow-up phone call about 30 days after taking the last dose of study drugs.

Conditions

Neoplasms

Study ID

NCT04449549

Start date

Aug 24, 2020

Status verified date

Aug 17, 2026

Completion date

Apr 8, 2027

Anticipated

Primary completion date

Apr 2, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

INCLUSION CRITERIA:
Patients must have histologically confirmed rare solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist. With Amendment G (v 6-17-24), eligibility will be limited to patients with adult granulosa cell ovarian cancer, clear cell ovarian cancer, anal cancer, or Ewing sarcoma. Patients must have measurable and evaluable disease.
Age >= 18 years.
ECOG performance status <= 2.
Patients must have normal organ and marrow function as defined below:

Absolute neutrophil count >=1,500/mcL
Platelets >=100,000/mcL
Total bilirubin <=1.5 X institutional ULN
AST(SGOT)/ALT(SGPT) <=3 X institutional upper limit of normal; <= 5.0 x ULN in patients with liver metastases
creatinine <=1.5 X institutional ULN OR
creatinine clearance >=60 mL/min/1.73 m\^2 for patients with creatinine levels >1.5 mg/dL
Nilotinib and paclitaxel have both been assigned to pregnancy category D by the FDA. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for at least 3 months after dosing with study drugs ceases. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of study drug administration.
Patients must have completed radiation therapy or major surgery >= 3 weeks, or biologic therapy or chemotherapy >= 5 half-lives or 3 weeks, whichever is shorter (6 weeks for nitrosoureas and mitomycin C) prior to entering the study. Patients must be >= 2 weeks since any prior administration of a study drug in a Phase 0 or equivalent study and be >= 1 week from palliative radiation therapy (patients on study may be eligible for palliative radiotherapy to non-targeted lesions after 2 cycles of therapy at the PI's discretion). Patients must have recovered to eligibility levels from prior toxicity or adverse events. Treatment with bisphosphonates is permitted.
Biopsies are optional on this study. In lieu of baseline biopsies, patients are encouraged to submit at registration archival tumor biopsy tissue from a previous research study or medical care providing it meets the minimum collection and preservations requirements outlined for the submission of archival tissue are:

Tissue must have been collected within 3 months prior to registration.
Patient must not have received any intervening therapy for their cancer since the collection of the tumor sample.
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. For these patients, an HIV viral load test must be completed within 28 days prior to enrollment.

EXCLUSION CRITERIA:

QTcF interval of >=450 msec at study entry; congenital long QT syndrome
Sensory/motor neuropathy >= Grade 2
Patients who are receiving any other investigational agents.
Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:

Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:

Evaluable or measurable disease outside the CNS
No metastases to brain stem, midbrain, pons, medulla, or cerebellum
No history of intracranial hemorrhage or spinal cord hemorrhage
No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted.
No neurosurgical resection or brain biopsy within 28 days prior to Cycle 1, Day 1
Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:

Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and radiographic screening for the current study
No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle 1, Day 1
Screening CNS radiographic study >=4 weeks from completion of radiotherapy and >=2 weeks from discontinuation of corticosteroids
History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs.
Uncontrolled intercurrent illness including, but not limited to, serious untreated infection, symptomatic respiratory failure/congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because nilotinib and paclitaxel have been assigned to pregnancy category D by the FDA. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 3 months following the last dose of study drug.

Study Design

Enrollment

82 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 1

Nilotinib will be administered at 300 mg orally BID; Paclitaxel will be administered IV at 80 mg/m\^2 on Days 1, 8, and 15 in 28-day cycles.

Interventions

Nilotinib and Paclitaxel

The BCR-Abl kinase inhibitor nilotinib demonstrated greater than additive activity in combination with the anti-tubulin agent paclitaxel in preclinical xenograft models, justifying the clinical evaluation of this combination for its antitumor activity

Primary outcome measure

Objective response [ Time Frame: 12 months ]

Central Contacts and Locations

Central contacts

Brooksley F Augustine

(240) 858-3197 brooke.augustine@nih.gov

Alice P Chen, M.D.

(240) 781-3320 chenali@mail.nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

888-624-1937

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 8, 2026

Last verified

Aug 17, 2026

Keywords

Pharmacodynamic
BCR Abl kinase inhibitor
Taxanes
Combination

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-08.