Cisplatin, Docetaxel, and Nintedanib Before Surgery in Treating Patients With Previously Untreated Stage IB-IIIA Non-small Cell Lung Cancer

NCT02225405 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2013-0844NCI-2014-02091
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of nintedanib when given together with cisplatin and docetaxel and to see how well they work in treating patients with previously untreated stage IB-IIIA non-small cell lung cancer who are undergoing surgery. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cisplatin, docetaxel, and nintedanib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Conditions

Stage IB Non-Small Cell Lung Carcinoma AJCC v7; Stage II Non-Small Cell Lung Cancer AJCC v7; Stage IIA Non-Small Cell Lung Carcinoma AJCC v7; Stage IIB Non-Small Cell Lung Carcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of nintedanib

  Will be determined according to incidence of dose-limiting toxicity as graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.

  21 days

• Major pathologic response rate, defined as less than or equal to 10% viable tumor cells in the resected specimen using the methods described by Pataer

  Multivariate analysis will be used to explore the role of biomarkers in predicting pathologic response to treatment, in an exploratory way.

  Up to 5 years

Secondary Outcomes (2)

• Change in tumor size (Expansion phase)

  Baseline to 4 weeks

• Response rate after single-agent nintedanib (Expansion phase)

  Up to 4 weeks

Study Arms (1)

Treatment (cisplatin, docetaxel, nintedanib)

EXPERIMENTAL

RUN-IN PHASE: Patients receive induction therapy comprising cisplatin IV over 2 hours on day 1, docetaxel IV over 1 hour on day 1, and nintedanib PO BID from day 2 of course 1 to day 7 of course 3. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. EXPANSION PHASE: Patients receive single-agent nintedanib PO BID on days 1-28. Patients then receive 3 courses of induction chemotherapy and undergo surgery as above. Treatment continues even if patients experience disease progression, unless treatment is judged to be not in the best interest of the patient by the treating physician.

Drug: Cisplatin; Drug: Docetaxel; Other: Laboratory Biomarker Analysis; Drug: Nintedanib

Interventions

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Treatment (cisplatin, docetaxel, nintedanib)

Docetaxel DRUG

Given IV

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Treatment (cisplatin, docetaxel, nintedanib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cisplatin, docetaxel, nintedanib)

Nintedanib DRUG

Given PO

Also known as: BIBF 1120, BIBF-1120, Intedanib, Multitargeted Tyrosine Kinase Inhibitor BIBF 1120, tyrosine kinase inhibitor BIBF 1120, Vargatef

Treatment (cisplatin, docetaxel, nintedanib)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed non-small cell lung cancer; patients with a suspected lung cancer are eligible, but pathology must be confirmed prior to initiating treatment on study; neuroendocrine carcinomas are not eligible; carcinomas with neuroendocrine differentiation are eligible
• Stage IB (with a primary tumor \>= 4 cm), IIA, IIB, or IIIA (according to American Joint Committee on Cancer \[AJCC\] 7th edition); patients with stage IIIA must not have more than one mediastinal lymph node station involved by tumor
• All patients must have lymph node evaluation of contralateral stations 2 and/or 4 to exclude N3 disease
• The patient must be a suitable candidate for surgery, in the opinion of the treating physician
• Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
• Signed and dated written informed consent prior to admission to the study in accordance with International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)-Good Clinical Practice (GCP) guidelines and to the local legislation

You may not qualify if:

• Prior systemic therapy or radiation therapy for treatment of the current lung cancer
• Known hypersensitivity to the trial drugs or to their excipients
• Centrally located tumors with radiographic evidence (CT or magnetic resonance imaging \[MRI\]) of local invasion of major blood vessels
• Major injuries within the past 10 days prior to start of study treatment with incomplete wound healing
• History of clinically significant hemorrhagic or thromboembolic event in the past 6 months
• Known inherited predisposition to bleeding or thrombosis
• Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure \> New York Heart Association \[NYHA\] II, serious cardiac arrhythmia, pericardial effusion)
• Creatinine \> 1.5 x the upper limit of normal; patients with creatinine \> 1.5 x the upper limit of normal who have creatinine clearance \>= 60 cc/min (calculated using the Cockcroft and Gault equation) are eligible
• Total bilirubin \> institutional upper limit of normal or
• Aspartate aminotransferase (AST) \> 1.5 x institutional upper limit of normal
• International normalized ratio (INR) \> 2
• Prothrombin time (PT) and partial thromboplastin time (PTT) \> 50% of deviation of institutional upper limit of normal (ULN)
• Absolute neutrophil count (ANC) \< 1500/ml, and/or
• Platelets \< 100000/ml
• Prior malignancy requiring systemic therapy or radiation therapy within 1 year of randomization

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Docetaxel; nintedanib

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)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Tina Cascone

  M.D. Anderson Cancer Center

  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

Study Record Dates

• First Submitted: August 22, 2014
• First Posted: August 26, 2014
• Study Start: April 3, 2015
• Primary Completion: May 6, 2024
• Study Completion: May 6, 2024
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

US (1)