Phase 1 Erlotinib and Dovitinib (TKI258) in Advanced Non-small Cell Lung Cancer (NSCLC)

NCT01515969 | Terminated Phase 1 DMC

• 5 other identifiers: IRB-21659IRB-18952LUN0044NCI-2011-03333SU-08012011-8166
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of giving erlotinib and dovitinib together to treat patients with metastatic non-small cell lung cancer. Erlotinib blocks the epidermal growth factor receptor (EGFR) and has known activity in non-small cell lung cancer and dovitinib blocks the fibroblast growth factor receptor (FGFR) and other targets which may be important to treat lung cancer. The combination of both drugs may work better than either drug alone, but may also have increased side effects. This trial will look at the side effects of combining the drugs and look for how effective the combination may be.

Conditions

Non-small Cell Lung Cancer (NSCLC), Recurrent; Non-small Cell Lung Cancer (NSCLC), Stage IV

Outcome Measures

Primary Outcomes (1)

• Measure toxicity to determine the MTD of the combination of erlotinib hydrochloride and dovitinib lactate

  Dose limiting toxicity (DLT) is defined as a CTCAE v4.0 toxicity \>= grade 3 or 4 occurring after 3 weeks of treatment. If 2 of 6 patients experience a DLT, then the MTD will be defined as the dose tolerated by the cohort preceding the cohort experiencing the DLT.

  1 year

Secondary Outcomes (3)

• ORR (complete response [CR]+ partial response [PR])

  1 year

• PFS

  1 year

• OS

  1 year

Study Arms (1)

Treatment (enzyme inhibitor therapy)

EXPERIMENTAL

Patients receive erlotinib hydrochloride PO QD. Starting on day 15, patients also receive dovitinib lactate PO QD on days 1-5 of each week. Treatment continues in the absence of disease progression or unacceptable toxicity.

Drug: Erlotinib hydrochloride; Drug: Dovitinib lactate

Interventions

Erlotinib hydrochloride DRUG

Given PO

Also known as: Erlotinib HCl, Tarceva, CP-358,774, OSI-774

Treatment (enzyme inhibitor therapy)

Dovitinib lactate DRUG

Given PO

Also known as: CHIR-258, Receptor tyrosine kinase (RTK) inhibitor TKI258, TKI258

Treatment (enzyme inhibitor therapy)

Eligibility Criteria

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

You may qualify if:

• Histologically-confirmed metastatic non-small cell lung cancer
• One or more primary or metastatic lesions measurable in at least one dimension by modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria (v1.1) within 4 weeks prior to entry of study
• Patients who have failed any number of prior therapies, including those previously treated with erlotinib
• Life expectancy \> 2 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (\>= 1500/mm\^3)
• Platelets (PLT) \>= 100,000/mm\^3
• Hemoglobin (Hgb) \>= 9 g/dL
• Serum creatinine =\< 1.5 x upper limit of normal (ULN)
• Serum bilirubin =\< 1.5 x ULN (regardless of whether liver metastases are present at baseline)
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =\< 3.0 x ULN (regardless of whether liver metastases are present at baseline)
• Ability to understand and the willingness to provide verbal and written informed consent
• Patients - both males and females- with reproductive potential (i.e. menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study; women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration

You may not qualify if:

• Patients who have received the last administration of chemotherapy or immunotherapy =\< the timeframe defined below after the end of the cycle of the last treatment, prior to starting study drug, or who have not recovered from the side effects of such therapy:
• Patients who have received the last administration of chemotherapy/immunotherapy in a daily schedule =\< 7 days prior to starting study drug
• Patients who have received the last administration of chemotherapy/immunotherapy in a weekly schedule =\< 2 weeks prior to starting study drug
• Patients who have received the last administration of chemotherapy/immunotherapy in a 2-weekly schedule =\< 3 weeks prior to starting study drug
• Patients who have received the last administration of chemotherapy/immunotherapy in a 3-weekly schedule =\< 4 weeks prior to starting study drug
• Patients who have received the last administration of chemotherapy/immunotherapy in a 4-weekly schedule =\< 5 weeks prior to starting study drug
• Patients who have received the last administration of nitrosourea, mitomycin-C =\< 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
• Patients who have received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) =\< 4 weeks or limited field radiation for palliation =\< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• Patients who have undergone major surgery =\< 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• If history of other primary cancer, subject will be eligible only if she or he has:
• Curatively resected non-melanomatous skin cancer, basal cell carcinoma, squamous cell carcinoma
• Curatively treated cervical carcinoma in situ
• Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 3 years
• Subjects known to have chronic or active hepatitis B or C infection with impaired hepatic function (ineligible if AST and ALT \> 2.5 x ULN)
• History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results

Sponsors & Collaborators

• Heather Wakelee: lead
• Genentech, Inc.: collaborator
• Novartis: collaborator

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Recurrence

Interventions

Erlotinib Hydrochloride; 4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; Receptor Protein-Tyrosine Kinases

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Protein-Tyrosine Kinases; Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Cell Surface; Membrane Proteins

Study Officials

• Heather Wakelee

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: December 16, 2011
• First Posted: January 24, 2012
• Study Start: July 1, 2012
• Primary Completion: February 1, 2013
• Study Completion: December 1, 2014
• Last Updated: July 12, 2016

Record last verified: 2016-07

Locations

US (1)