NCT04449549 · National Cancer Institute (NCI)
Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors (RARE CANCER) Trial: RARE 1 Nilotinib and Paclitaxel
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
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 measures
Objective response
Time frame: 12 months
If at least 4/30 patients experience an objective response, defined as a complete or partial response by RECIST 1.1, the combination of nilotinib and paclitaxel will be considered promising. This design provides approximately 88% power to reject a null ORR of 0.05 when the true ORR is 0.2 (with one-sided type-I error of approximately 0.062).
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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. The list of eligible rare tumors can be found below\*\*. 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.
- Rare Tumor Eligibility List
- Epithelial tumors of nasal cavity, sinuses, nasopharynx
- Epithelial tumors of major salivary glands
- Salivary gland type tumors of head and neck, lip, esophagus, stomach, trachea and lung, breast and other location
- Undifferentiated carcinoma of gastrointestinal (GI) tract
- Adenocarcinoma with variants of small intestine
- Squamous cell carcinoma with variants of GI tract (stomach small intestine, colon, rectum, pancreas)
- Fibromixoma and low-grade mucinous adenocarcinoma (pseudomixoma peritonei) of the appendix and ovary
- Rare Pancreatic tumors including acinar cell carcinoma, mucinous cystadenocarcinoma or serous cystadenocarcinoma
- Intrahepatic cholangiocarcinoma
- Extrahepatic cholangiocarcinoma and bile duct tumors
- Sarcomatoid carcinoma of lung
- Bronchoalveolar carcinoma lung (a.k.a. adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma, or invasive mucinous adenocarcinoma)
- Non-epithelial tumors of the ovary
- Trophoblastic tumor
- Transitional cell carcinoma other than that of the renal, pelvis, ureter, or bladder
- Cell tumor of the testes and extragonadal germ tumors
- Epithelial tumors of penis - squamous adenocarcinoma cell carcinoma with variants of penis
- Squamous cell carcinoma variants of the genitourinary (GU) system
- Spindle cell carcinoma of kidney, pelvis, ureter
- Adenocarcinoma with variants of GU system (excluding prostate cancer)
- Odontogenic malignant tumors
- Pancreatic neuroendocrine tumor (PNET)
- Neuroendocrine carcinoma including carcinoid of the lung
- Pheochromocytoma, malignant
- Paraganglioma
- Carcinomas of pituitary gland, thyroid gland parathyroid gland and adrenal cortex
- Desmoid tumors
- Peripheral nerve sheath tumors and NF1-related tumors
- Malignant giant cell tumors
- Adrenal cortical tumors
- Tumor of unknown primary (Cancer of Unknown Primary; CuP)
- Not Otherwise Categorized (NOC) Rare Tumors
- Adenoid cystic carcinoma
- Vulvar cancer
- MetaPLASTIC carcinoma (of the breast)
- Gastrointestinal stromal tumor (GIST)
- Perivascular epithelioid cell tumor (PEComa)
- Apocrine tumors/Extramammary Paget s Disease
- Peritoneal mesothelioma
- Basal cell carcinoma
- Clear cell cervical cancer
- Esthenioneuroblastoma
- Endometrial carcinosarcoma (malignant mixed Mullerian tumors)
- Clear cell endometrial cancer
- Clear cell ovarian cancer
- Gestational trophoblastic disease (GTD)
- Gallbladder cancer
- Small cell carcinoma of the ovary, hypercalcemic type
- Angiosarcoma
- High-grade neuroendocrine carcinoma
- Treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC)
- Anal cancer
- Merkel cell carcinoma
- Pleural Mesothelioma
- Sarcoma (bone \& soft tissue)
- Thymic Carcinoma
- Uterine Leiomyosarcoma
- Papillary RCC
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.
Where
- Bethesda, Maryland
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 22, 2026 · Source of record for eligibility and locations