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

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Recruiting
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34
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National Cancer Institute (NCI)

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Updated on 19 February 2024

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cancer

epinephrine

metastasis

solid tumour

neutrophil count

squamous cell carcinoma

paclitaxel

sarcoma

liver metastasis

ovarian cancer

adenocarcinoma

bisphosphonate

lymphoma

nilotinib

carcinoma

urine test

mitomycin

nitrosoureas

major surgery

electrocardiogram

antineoplastic agents

transitional cell carcinoma

biopsy tissue

gastrointestinal stromal tumor

angiosarcoma

cavities

adenoid cystic carcinoma

solid neoplasm

advanced cancer

dental caries

mixed mullerian tumors

carcinosarcoma

serous cystadenocarcinoma

mucinous adenocarcinoma

liver metastases

undifferentiated carcinoma

cholangiocarcinoma

neuroendocrine tumor

neuroendocrine carcinoma

small intestine

gist

pancreatic neuroendocrine tumor

peritoneal mesothelioma

thymic carcinoma

pleural mesothelioma

palliative radiation therapy

chordoma

giant cell tumors

pheochromocytoma, malignant

desmoid tumors

carcinoma lung

carcinoid

lepidic predominant adenocarcinoma

spindle cell carcinoma of kidney

merkel cell carcinoma

adrenal

prostate cancer

cervical cancer

small cell lung cancer

endometrial cancer

gestational trophoblastic disease

parathyroid gland

mucinous cystadenocarcinoma

endometrial carcinosarcoma

vulvar cancer

pancreatic tumors

acinar cell carcinoma

bronchioloalveolar carcinoma

malignant mixed mullerian tumor

carcinoma, ovarian epithelial

Summary

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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.

Description

Background

Rare tumors constitute a heterogeneous group of cancers associated with limited treatment options and poor outcomes. Due to their rarity, there are few good models for these diseases to support preclinical evaluation of new anticancer agents. To address these challenges, DCTD s Patient-Derived Models Repository (PDMR) is generating patient-derived xenograft models of adult and pediatric rare cancers and has screened combinations of approved and investigational anticancer agents in these models.
Based on preclinical activity, drug combinations are being tested in patients with rare cancers in a series of connected Phase 2 clinical trials (Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors [RARE CANCER]); responses may trigger further evaluation of a treatment in that rare cancer type to further evaluate response rate and mechanism-of-action. Patients who progress will be offered another RARE CANCER trial.
The agents used in this trial are the BCR-Abl kinase inhibitor nilotinib and the anti-tubulin agent paclitaxel, which showed greater than additive activity in combination in preclinical xenograft models and subsequently demonstrated clinical efficacy (including partial responses) in patients with solid tumors on the Phase 1 trial 15-C-0086 (NCT02379416).

Primary Objectives:

To evaluate the proportion of patients with advanced rare cancers who have objective responses (OR) to treatment with nilotinib and paclitaxel

Exploratory Objectives:

To evaluate the proportion of patients alive and progression free at 6 months on study agents
To identify genomic and transcriptomic determinants of response and resistance in tumor biopsy specimens
To examine genomic alterations in circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) that may be associated with response or resistance
To evaluate the pharmacodynamic effects of the combination on biomarkers of cell death and epithelial-to-mesenchymal transition in tumor tissue and CTCs

Eligibility
Study participants must have a histologically confirmed solid tumor meeting the RARECARE definition of rare tumor that has progressed on standard therapy known to prolong survival or for which no standard treatment options exist
Age >= 18
No major surgery, radiation, or chemotherapy within 3 weeks prior to entering the study (6 weeks for nitrosoureas and mitomycin C) or 5 half-lives of the agent, whichever is shorter; toxicity from prior treatment must have recovered to eligibility levels.
Adequate organ function; performance status ECOG 0-2

Study Design:

Nilotinib will be administered at 300 mg orally BID and paclitaxel will be administered IV at 80 mg/m2 on Days 1, 8, and 15 in 28-day cycles.
A single-stage design will be used with a target accrual of 30 eligible patients. If at least 4/30 patients experience an objective response (PR or CR by RECIST 1.1), the combination of nilotinib and paclitaxel will be considered promising. The accrual ceiling is 34 patients.

Details

Condition	Cancer
Age	18years - 120years
Treatment	Paclitaxel, Nilotinib
Clinical Study Identifier	NCT04449549
Sponsor	National Cancer Institute (NCI)
Last Modified on	19 February 2024

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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; other rare tumor types may be acceptable at the discretion of the PI
	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 in Section [5.1.3.4](telnet://5.1.3.4). Criteria 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
	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
	Chordoma
	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
	Lymphoma
	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
	Patients who are known to be HIV-positive and on combination antiretroviral therapy are ineligible because of possible PK interactions with study drugs

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adenoid cystic carcinoma

solid neoplasm

advanced cancer

dental caries

mixed mullerian tumors

carcinosarcoma

serous cystadenocarcinoma

mucinous adenocarcinoma

liver metastases

undifferentiated carcinoma

cholangiocarcinoma

neuroendocrine tumor

neuroendocrine carcinoma

small intestine

gist

pancreatic neuroendocrine tumor

peritoneal mesothelioma

thymic carcinoma

pleural mesothelioma

palliative radiation therapy

chordoma

giant cell tumors

pheochromocytoma, malignant

desmoid tumors

carcinoma lung

carcinoid

lepidic predominant adenocarcinoma

spindle cell carcinoma of kidney

merkel cell carcinoma

adrenal

prostate cancer

cervical cancer

small cell lung cancer

endometrial cancer

gestational trophoblastic disease

parathyroid gland

mucinous cystadenocarcinoma

endometrial carcinosarcoma

vulvar cancer

pancreatic tumors

acinar cell carcinoma

bronchioloalveolar carcinoma

malignant mixed mullerian tumor

carcinoma, ovarian epithelial

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