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Testing JNJ-42756493 (Erdafitinib) as Potentially Targeting Treatment in Cancers With FGFR Amplifications (MATCH-Subprotocol K1)

Study Purpose

This phase II MATCH treatment trial tests how well JNJ-42756493 (erdafitinib) works in treating patients with tumors that have more copies of the FGFR gene than is normal (amplification). Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein that signals cancer cells to multiply.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol.
  • - Patients must fulfill all eligibility criteria outlined in MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7).
  • - Patients must have FGFR Amplification as determined via the MATCH Master Protocol.
  • - Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block).
  • - Patients must not have known hypersensitivity to JNJ-42756493 (erdafitinib) or compounds of similar chemical or biologic composition.
  • - Patients with current evidence of corneal or retinal disorder/keratopathy are excluded.
  • - Patients must not be currently using medications that can elevate serum phosphorous and/or calcium levels.
  • - Medications that increase serum calcium should be avoided.
Over the counter calcium supplements, antacids that contain calcium (Tums) and vitamin D supplements (cholecalciferol and ergocalciferol) should be avoided. Prescription medications including lithium, hydrochlorothiazide and chlorthalidone must be used with caution.
  • - Medications that increase serum phosphate should be avoided.
Over the counter laxatives that contain phosphate such as Fleets oral or Fleets enema and Miralax should be avoided.
  • - Patients with a history of hyperphosphatemia will be excluded.
  • - Patients may not have received strong inhibitors or potent inducers of CYP3A within 2 weeks before the first dose of study treatment.
Patients with inability to discontinue treatment with a strong CYP3A4 and/or CYP2C9 inhibitor or inducer prior to start of treatment are excluded.
  • - Patients who have previously received treatment with a FGFR-targeted inhibitor are excluded.
Such inhibitors include AZD4547, BGJ398, BAY1163877 and LY2874455). Prior non-selective FGFR inhibitor treatment (e.g. Pazopanib, dovitinib, ponatinib, brivanib, lucitanib, lenvatinib) are allowed.
  • - Patients must not have any history of or current evidence of renal or endocrine alterations of calcium/phosphate homeostasis, or history of or current evidence of extensive tissue calcification (by evaluation of the clinician), including but not limited to, the soft tissue, kidneys, intestine, myocardium and lung with the exception of calcified lymph nodes and asymptomatic vascular calcification per investigators' judgment.
  • - Patients with transitional cell carcinoma of the bladder and /or urothelial tract are not eligible.
These patients are encouraged to enroll in the ongoing disease-specific studies.
  • - Patients with impaired renal function (glomerular filtration rate [GFR] < 60 mL/min) are excluded.
GFR should be assessed by direct measurement (i.e., creatinine clearance or ethyldediaminetetraacetate) or, if not available, by calculation from serum/plasma creatinine (Cockcroft-Gault formula).
  • - Patients with persistent phosphate level > upper limit of normal (ULN) during screening (within 14 days of treatment and prior to cycle 1 day 1) and despite medical management are excluded.
  • - Patients with a history of or current uncontrolled cardiovascular disease as stated below are excluded: - Unstable angina, myocardial infarction, or known congestive heart failure class II-IV within the preceding 12 months; cerebrovascular accident or transient ischemic attack within the preceding 3 months, pulmonary embolism within the preceding 2 months.
  • - Any of the following: sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, cardiac arrest, Mobitz II second degree heart block or third degree heart block; known presence of dilated, hypertrophic, or restrictive cardiomyopathy.
  • - Patients with impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions are excluded.
  • - Female subjects (of child-bearing potential and sexually active) must use medically acceptable methods of birth control (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of the study, and for 4 months after the last intake of study drug.
Male subjects (with a partner of child-bearing potential) must use a condom with spermicide when sexually active and must not donate sperm from the first dose of study drug until 5 months after the last dose of study drug.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06308822
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

National Cancer Institute (NCI)
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Alain C Mita
Principal Investigator Affiliation ECOG-ACRIN Cancer Research Group
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

NIH
Overall Status Active, not recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma
Additional Details

PRIMARY OBJECTIVE:

  • I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.
SECONDARY OBJECTIVES:
  • I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.
  • II. To evaluate time until death or disease progression.
  • III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.
  • IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.
OUTLINE: Patients receive erdafitinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and magnetic resonance imaging (MRI) throughout study. Patients may also undergo blood sample collection and tumor biopsy throughout the trial. After completion of study treatment, patients are followed up every 3 months for 2 years then every 6 months for 1 year. THE MATCH SCREENING TRIAL: Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.

Arms & Interventions

Arms

Experimental: Treatment (erdafitinib)

Patients receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout study. Patients may also undergo blood sample collection and tumor biopsy throughout the trial.

Interventions

Procedure: - Biopsy

Undergo tumor biopsy

Procedure: - Biospecimen Collection

Undergo blood sample collection

Procedure: - Computed Tomography

Undergo CT

Drug: - Erdafitinib

Given PO

Procedure: - Magnetic Resonance Imaging

Undergo MRI

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

ECOG-ACRIN Cancer Research Group, Philadelphia, Pennsylvania

Status

Address

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, 19103