Cabozantinib-S-Malate and Erlotinib Hydrochloride in Treating Patients With Previously Treated Metastatic Non-Small Cell Lung Cancer

NCT01866410 | Completed Phase 2 Results DMC

• 5 other identifiers: NCI-2013-01085PHII-1259303N01CM00038P30CA033572
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 7

Brief Summary

This phase II trial studies how well cabozantinib-s-malate and erlotinib hydrochloride works in treating patients with previously treated metastatic non-small cell lung cancer. Cabozantinib-s-malate and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cabozantinib-s-malate may also stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. Giving cabozantinib-s-malate together with erlotinib hydrochloride may be an effective treatment for non-small cell lung cancer.

Conditions

Recurrent Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  Up to 2 years

Secondary Outcomes (5)

• Percentage of Patients With a Greater Than 30% Increase in Tumor Doubling Time

  Up to 2 years

• Number of Adverse Events

  Up to 2 years

• Best Response Patient Count

  Up to 2 years

• Progression-free Survival

  Until disease progression or death from any cause, up to 2 years

• Overall Survival

  Until death from any cause, up to 2 years

Other Outcomes (4)

• Progression-free Survival by T790M Mutation Status

  Until disease progression or death from any cause, up to 2 years

• Overall Survival by T790M Mutation Status

  Until death from any cause, up to 2 years

• Changes in VEGF Levels

  Baseline up to 6 months after last study treatment

Study Arms (1)

Treatment (cabozantinib-s-malate, erlotinib hydrochloride)

EXPERIMENTAL

Patients receive cabozantinib-s-malate PO daily and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib S-malate; Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis

Interventions

Cabozantinib S-malate DRUG

Given PO

Also known as: BMS-907351, Cabometyx, Cometriq, XL184

Treatment (cabozantinib-s-malate, erlotinib hydrochloride)

Erlotinib Hydrochloride DRUG

Given PO

Also known as: Cp-358,774, OSI-774, Tarceva

Treatment (cabozantinib-s-malate, erlotinib hydrochloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cabozantinib-s-malate, erlotinib hydrochloride)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed non-small cell lung cancer harboring an EGFR mutation; NOTE: EGFR mutational status will be known and assays performed in Clinical Laboratory Improvement Amendments (CLIA) certified laboratories will be accepted
• Patients should have tumor tissue available for retrieval; tissue blocks or unstained slides from the time of original diagnosis are acceptable if repeat biopsy is not indicated
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Patients must have received prior EGFR TKI therapy for metastatic disease and have documented evidence of radiologic disease progression while on EGFR TKI as treatment immediately prior to enrollment; (patients may have received prior chemotherapy, and retreatment with erlotinib is allowed)
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 60%)
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin =\< 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 × institutional upper limit of normal
• Lipase \< 2.0 x ULN and no radiologic or clinical evidence of pancreatitis
• Creatinine =\< 1.5 × ULN OR creatinine clearance \>= 50 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Hemoglobin \>= 9 g/dL
• Serum albumin \>= 2.8 g/dL
• Urine protein/creatinine ratio (UPCR) =\< 1

You may not qualify if:

• The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 3 weeks, or nitrosoureas/ mitomycin C within 6 weeks before the first dose of study treatment
• Prior treatment with XL184 (cabozantinib) or other MET/hepatocyte growth factor (HGF) inhibitor
• The subject has received radiation therapy:
• To the thoracic cavity, abdomen, or pelvis within 2 weeks before the first dose of study treatment, or has ongoing complications, or is without complete recovery and healing from prior radiation therapy
• To bone or brain metastasis within 14 days before the first dose of study treatment
• To any other site(s) within 28 days before the first dose of study treatment
• The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment; prior erlotinib is required and does not require a 14-day wash out
• The subject has received any other type of investigational agent within 28 days before the first dose of study treatment
• The subject has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =\< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)
• The subject has a primary brain tumor
• The subject has active brain metastases or epidural disease; subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible; baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility
• The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test \>= 1.3 x the laboratory ULN within 14 days before the first dose of study treatment
• The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel); low dose aspirin (=\< 81 mg/day), low-dose warfarin (=\< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted
• Strong cytochrome P450 (CYP)3A4 inducers and inhibitors should be avoided; selection of alternate concomitant medications with no or minimal CYP3A4 enzyme inhibition potential is recommended; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• The subject has experienced any of the following:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Reckamp KL, Frankel PH, Ruel N, Mack PC, Gitlitz BJ, Li T, Koczywas M, Gadgeel SM, Cristea MC, Belani CP, Newman EM, Gandara DR, Lara PN Jr. Phase II Trial of Cabozantinib Plus Erlotinib in Patients With Advanced Epidermal Growth Factor Receptor (EGFR)-Mutant Non-small Cell Lung Cancer With Progressive Disease on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy: A California Cancer Consortium Phase II Trial (NCI 9303). Front Oncol. 2019 Mar 11;9:132. doi: 10.3389/fonc.2019.00132. eCollection 2019.

  PMID: 30915273 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

cabozantinib; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-218-5265

Study Officials

• Karen Reckamp

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

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: May 28, 2013
• First Posted: May 31, 2013
• Study Start: May 20, 2013
• Primary Completion: March 30, 2018
• Study Completion: March 30, 2018
• Last Updated: May 16, 2019
• Results First Posted: May 16, 2019

Record last verified: 2019-04

Locations

US (7)