Testing nilotinib and paclitaxel for rare cancers

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

This study is testing a new combination of two drugs, nilotinib and paclitaxel, to see if it can help adults with rare solid tumors that haven't responded to other treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 82 (estimated)
• Ages: 18 Years to 120 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (nih)
• Drugs / interventions: Nilotinib, chemotherapy, radiation
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT04449549 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of a combination of nilotinib, a BCR-Abl kinase inhibitor, and paclitaxel, an anti-tubulin agent, in patients with rare solid tumors that have progressed after standard treatments or for which no effective therapies exist. Participants aged 18 and older will undergo screening, including medical history, physical exams, and imaging scans to assess their tumors. The trial will monitor the patients' responses to the drug combination, with the potential for further evaluation based on initial results. This approach leverages preclinical findings that suggest enhanced efficacy of the drug combination in treating rare cancers.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed rare solid tumors that have progressed after standard therapy or for which no standard treatment options exist.

Not a fit: Patients with rare cancers that have not progressed after standard treatments or those with tumors not included in the eligibility criteria may not benefit from this trial.

Why it matters

Potential benefit: If successful, this trial could provide a new treatment option for patients with rare cancers that currently have limited therapeutic alternatives.

How similar studies have performed: Other studies have shown promising results with similar drug combinations in treating solid tumors, indicating potential for success in this novel application for rare cancers.

Eligibility criteria

* 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

    1. Epithelial tumors of nasal cavity, sinuses, nasopharynx
    2. Epithelial tumors of major salivary glands
    3. Salivary gland type tumors of head and neck, lip, esophagus, stomach, trachea and lung, breast and other location
    4. Undifferentiated carcinoma of gastrointestinal (GI) tract
    5. Adenocarcinoma with variants of small intestine
    6. Squamous cell carcinoma with variants of GI tract (stomach small intestine, colon, rectum, pancreas)
    7. Fibromixoma and low-grade mucinous adenocarcinoma (pseudomixoma peritonei) of the appendix and ovary
    8. Rare Pancreatic tumors including acinar cell carcinoma, mucinous cystadenocarcinoma or serous cystadenocarcinoma
    9. Intrahepatic cholangiocarcinoma
    10. Extrahepatic cholangiocarcinoma and bile duct tumors
    11. Sarcomatoid carcinoma of lung
    12. Bronchoalveolar carcinoma lung (a.k.a. adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma, or invasive mucinous adenocarcinoma)
    13. Non-epithelial tumors of the ovary
    14. Trophoblastic tumor
    15. Transitional cell carcinoma other than that of the renal, pelvis, ureter, or bladder
    16. Cell tumor of the testes and extragonadal germ tumors
    17. Epithelial tumors of penis - squamous adenocarcinoma cell carcinoma with variants of penis
    18. Squamous cell carcinoma variants of the genitourinary (GU) system
    19. Spindle cell carcinoma of kidney, pelvis, ureter
    20. Adenocarcinoma with variants of GU system (excluding prostate cancer)
    21. Odontogenic malignant tumors
    22. Pancreatic neuroendocrine tumor (PNET)
    23. Neuroendocrine carcinoma including carcinoid of the lung
    24. Pheochromocytoma, malignant
    25. Paraganglioma
    26. Carcinomas of pituitary gland, thyroid gland parathyroid gland and adrenal cortex
    27. Desmoid tumors
    28. Peripheral nerve sheath tumors and NF1-related tumors
    29. Malignant giant cell tumors
    30. Chordoma
    31. Adrenal cortical tumors
    32. Tumor of unknown primary (Cancer of Unknown Primary; CuP)
    33. Not Otherwise Categorized (NOC) Rare Tumors
    34. Adenoid cystic carcinoma
    35. Vulvar cancer
    36. MetaPLASTIC carcinoma (of the breast)
    37. Gastrointestinal stromal tumor (GIST)
    38. Perivascular epithelioid cell tumor (PEComa)
    39. Apocrine tumors/Extramammary Paget s Disease
    40. Peritoneal mesothelioma
    41. Basal cell carcinoma
    42. Clear cell cervical cancer
    43. Esthenioneuroblastoma
    44. Endometrial carcinosarcoma (malignant mixed Mullerian tumors)
    45. Clear cell endometrial cancer
    46. Clear cell ovarian cancer
    47. Gestational trophoblastic disease (GTD)
    48. Gallbladder cancer
    49. Small cell carcinoma of the ovary, hypercalcemic type
    50. Angiosarcoma
    51. High-grade neuroendocrine carcinoma
    52. Treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC)
    53. Anal cancer
    54. Lymphoma
    55. Merkel cell carcinoma
    56. Pleural Mesothelioma
    57. Sarcoma (bone \& soft tissue)
    58. Thymic Carcinoma
    59. Uterine Leiomyosarcoma
    60. 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 this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (RECRUITING)

Study contacts

• Principal investigator: Alice P Chen, M.D. — National Cancer Institute (NCI)
• Study coordinator: Brooksley F Augustine

Conditions: Neoplasms, Pharmacodynamic, BCR Abl kinase inhibitor, Taxanes, Combination