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

NCT04449549 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 20012120-C-0121
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

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

Keywords

Pharmacodynamic; BCR Abl kinase inhibitor; Taxanes; Combination

Outcome Measures

Primary Outcomes (1)

• Objective response

  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).

  12 months

Study Arms (1)

1

EXPERIMENTAL

Nilotinib will be administered at 300 mg orally BID; Paclitaxel will be administered IV at 80 mg/m2 on Days 1, 8, and 15 in 28-day cycles.

Drug: Nilotinib and Paclitaxel

Interventions

Nilotinib and Paclitaxel DRUG

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

1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (1)

• Kummar S, Chen HX, Wright J, Holbeck S, Millin MD, Tomaszewski J, Zweibel J, Collins J, Doroshow JH. Utilizing targeted cancer therapeutic agents in combination: novel approaches and urgent requirements. Nat Rev Drug Discov. 2010 Nov;9(11):843-56. doi: 10.1038/nrd3216. Epub 2010 Oct 29.

  PMID: 21031001 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neoplasms

Interventions

nilotinib; Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Alice P Chen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brooksley F Augustine

CONTACT

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

Alice P Chen, M.D.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2020
• First Posted: June 29, 2020
• Study Start: August 24, 2020
• Primary Completion (Estimated): April 2, 2027
• Study Completion (Estimated): April 8, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04-23

Locations

US (1)