Erlotinib in Combination With Select Tyrosine Kinase Inhibitors in Adult Patients With Advanced Solid Tumors

NCT06161558 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 10001657001657-C
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Cancers that return or spread after their first line of treatment are often difficult to treat with limited next step options. Based on preclinical studies, the EGFR-targeting tyrosine kinase inhibitor (TKI) Erlotinib may be better in stopping or slowing the growth of tumors when given in combination with the multitargeting TKI Lenvatinib or Axitinib. Participants will be screened with a physical exam and tests including urine and blood tests, imaging scans, and a test of their heart function. Erlotinib, axitinib, and lenvatinib are all capsules taken by mouth. All participants will take their drugs at home every day. Some participants will take erlotinib plus lenvatinib once a day. Some participants will take erlotinib once a day and axitinib twice a day. Assignment to one of the treatment arms will be determined by the study. Participants will record their doses in a diary. Treatment is given in 28-day cycles. All participants will have 4 clinic visits during their first treatment cycle. After that, they will have a clinic visit at the start of each new cycle. Imaging scans, blood and urine tests, and other tests will be repeated during various clinic visits. Participants will remain in the study for as long as the treatment is helping them. They will have follow-up phone calls after they stop treatment....

Conditions

Neoplasms

Keywords

Kinase Inhibitor; Combination; Pharmacodynamic; TKI

Outcome Measures

Primary Outcomes (1)

• To establish the safety, tolerability, and maximum tolerated dose (MTD) of the erlotinib-lenvatinib and erlotinib-axitinib combinations in adult patients with advanced solid tumors

  This is an open-label phase 1 umbrella trial with 2 treatment arms. All agents will be administered orally in 28-day cycles. The starting dose level (DL) will be DL 1A for Arm A (the erlotinib-lenvatinib combination arm) and DL 1B for Arm B (the erlotinib-axitinib combination arm). Dose escalation on both arms will follow a 3+3 design. Intrapatient dose escalation to the next highest cleared dose level will be permitted upon completion of \>= 1 cycle of therapy at the current dose level at which the patient is being treated. Dose-limiting toxicities will be defined during the first cycle of treatment. Patients will be assigned to one of the two treatment arms in an alternating fashion.

  30 months

Secondary Outcomes (1)

• To evaluate the plasma pharmacokinetic profiles of erlotinib and either lenvatinib or axitinib when used in combination

  30 months

Study Arms (2)

A

EXPERIMENTAL

Erlotinib with lenvatinib combination

Drug: Erlotinib; Drug: Lenvatinib

B

EXPERIMENTAL

Erlotinib with axitinib combination

Drug: Erlotinib; Drug: Axitinib

Interventions

Erlotinib DRUG

Small-molecule tyrosine kinase inhibitor targeting EGFR

A; B

Lenvatinib DRUG

Small-molecule tyrosine kinase inhibitor targeting VEGFR1, VEGFR2, and VEGFR3

A

Axitinib DRUG

Small-molecule tyrosine kinase inhibitor targeting VEGFR1, VEGFR2, and VEGFR3

B

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 solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist.
• Age \>=18 years.
• Patients must have evaluable disease according to RECIST 1.1 criteria.
• 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 (with the exception of those with Gilbert syndrome, who must have total bilirubin \<=3 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
• creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels \>1.5 mg/dL
• Based on preclinical safety data and their respective mechanisms of action, erlotinib, lenvatinib, and axitinib can cause fetal harm when administered to pregnant women. For this reason, women of child-bearing potential and men enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 1 month 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.
• Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment.
• Patients with non-healing wounds/fistulas may enroll if no immediate surgical input is required in the opinion of the PI.
• Patients must have \<= 1+ proteinuria on urinalysis, or \< 1 g protein on 24-hour urine collection, or a urine protein:creatinine ratio of \< 1.

You may not qualify if:

• For the erlotinib-lenvatinib arm only: patients with a QTcF interval of \>=480 msec at study entry or with congenital long QT syndrome are excluded.
• Patients who are receiving any investigational agents are excluded.
• Patients who are receiving \>2 anti-hypertensive agents will be excluded.
• Patients who are receiving strong CYP3A4- and/or CYP1A2-inhibiting or -inducing agents that cannot be discontinued or replaced with an alternative medication will be excluded.
• Patients who are receiving agents that increase gastric pH and that cannot be discontinued or replaced with an alternative medication will be excluded.
• Patients who smoke tobacco will be excluded.
• Patients with a history of cirrhosis will be excluded if found to have a moderate or severe Child-Pugh score.
• Patients should not, in the opinion of the Principal Investigator, have GI impairment that may limit the absorption of erlotinib, lenvatinib, or axitinib.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs.
• Uncontrolled intercurrent illness that would, in the opinion of the Principal Investigator, limit compliance with study requirements.
• Pregnant and breastfeeding women are excluded from this study because all 3 study drugs can cause fetal harm, based on preclinical safety data and the respective drug mechanisms of action. 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 1 month following the last dose of study drug.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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

• Conradt L, Godl K, Schaab C, Tebbe A, Eser S, Diersch S, Michalski CW, Kleeff J, Schnieke A, Schmid RM, Saur D, Schneider G. Disclosure of erlotinib as a multikinase inhibitor in pancreatic ductal adenocarcinoma. Neoplasia. 2011 Nov;13(11):1026-34. doi: 10.1593/neo.111016.

  PMID: 22131878 BACKGROUND

• Augustin A, Lamerz J, Meistermann H, Golling S, Scheiblich S, Hermann JC, Duchateau-Nguyen G, Tzouros M, Avila DW, Langen H, Essioux L, Klughammer B. Quantitative chemical proteomics profiling differentiates erlotinib from gefitinib in EGFR wild-type non-small cell lung carcinoma cell lines. Mol Cancer Ther. 2013 Apr;12(4):520-9. doi: 10.1158/1535-7163.MCT-12-0880. Epub 2013 Jan 31.

  PMID: 23371860 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neoplasms

Interventions

Erlotinib Hydrochloride; lenvatinib; Axitinib

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Sarah J Shin, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2023
• First Posted: December 8, 2023
• Study Start: July 15, 2025
• Primary Completion: July 15, 2025
• Study Completion: July 15, 2025
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Requests for all collected IPD data from clinical trials, conducted under a binding collaborative agreement between NCI/DCTD and a pharmaceutical/biotechnology company, that are not under DSMB monitoring must be in compliance with the terms of the binding collaborative agreement and must be approved by NCI /DCTD and any Pharmaceutical Collaborator.

Locations

US (1)