Vorinostat, Paclitaxel, and Radiation Therapy in Treating Patients Unable to Tolerate Cisplatin With Stage III Non-Small Lung Cancer That Cannot Be Removed By Surgery

NCT00662311 | Terminated Phase 1 Results

• 2 other identifiers: 6600NCI-2010-00715
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of vorinostat when given together with paclitaxel and radiation therapy and to see how well it works in treating patients unable to tolerate cisplatin with stage III non-small cell lung cancer (NSCLC) that cannot be removed by surgery. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vorinostat together with paclitaxel and radiation therapy may kill more tumor cells

Conditions

Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• MTD of Vorinostat When Administered in Combination With Paclitaxel and Radiotherapy Therapy as Assessed by NCI Common Toxicity Criteria for Adverse Events (CTCAE) Version 3.0 (Phase I)

  Defined as the highest dose level at which no more than 1 of 6 patients experiences dose-limiting toxicity (DLT). Toxicity was graded according to the National Institutes of Health Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. A DLT was defined as any Grade 3 or higher non-hematologic adverse event with the exception of alopecia, fatigue, or anorexia. Nausea and/or vomiting that persisted \> 48 hours despite optimal medical management at grade 3 or higher was considered a DLT. Hematologic dose-limiting toxicity was defined as either: Grade 4 neutropenia lasting for ≥ 7 days in duration, Grade \> 3 febrile neutropenia with/without infection, Grade 4 thrombocytopenia or Grade 5 hematologic toxicity.

  8 weeks

Secondary Outcomes (5)

• Radiological Response Rate as Assessed by CT

  12 weeks post-treatment, then every 3 months for 2 years, and then every 6 months for a year thereafter

• Duration of Response

  Up to 3 years

• Progression-free Survival

  1 year

• Overall Survival

  1 year

• Safety and Toxicity of Vorinostat at the MTD as Assessed by NCI CTCAE Version 3.0

  Weekly during treatment, 30 days post-treatment, and 12 weeks post-treatment

Study Arms (1)

Treatment (vorinostat with paclitaxel and radiotherapy)

EXPERIMENTAL

Patients receive vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.

Drug: vorinostat; Drug: paclitaxel; Radiation: radiation therapy

Interventions

vorinostat DRUG

Given PO

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Treatment (vorinostat with paclitaxel and radiotherapy)

paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, TAX, Taxol

Treatment (vorinostat with paclitaxel and radiotherapy)

radiation therapy RADIATION

Undergo radiation therapy

Also known as: irradiation, radiotherapy, therapy, radiation

Treatment (vorinostat with paclitaxel and radiotherapy)

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 proven diagnosis of NSCLC
• Inoperable Stage IIIA or IIIB (excluding malignant pleural effusion) disease according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Sixth edition (2002)
• At least one site of measurable disease, as defined by the modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Inability to tolerate full dose cisplatin as defined by:
• Creatinine clearance less than 50ml/min
• Greater than grade 2 sensory hearing loss (as defined by National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] criteria v3.0 adverse event term "Hearing: Patients without baseline audiogram and not enrolled in a monitoring program")
• Performance status \>= 2
• Age \>= 75 years
• Cardiac history, such as myocardial infarction within 6 months, angina, or heart disease as defined by the New York Heart Association (NYHA) Class III or IV
• Any other comorbid disease or condition that would increase the risk of toxicity of cisplatin therapy
• Female patient is either post menopausal, free from menses for \>= 2 years, surgically sterilized or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study
• Female patient of childbearing potential has a negative serum pregnancy test beta-human chorionic gonadotropin (hCG) within 7 days prior to receiving the first dose of vorinostat
• Male patient agrees to use an adequate method of contraception for the duration of the study
• Absolute neutrophil count (ANC) \>= 1,500/mcL

You may not qualify if:

• Patient who has had chemotherapy, radiotherapy, or biological therapy for NSCLC within 5 years prior to initial dosing with study drug(s)
• Symptomatic neuropathy (\>= grade 2)
• Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug(s)
• Patient had prior treatment with an histone deacetylases (HDAC) inhibitor (e.g., romidespsin \[Depsipeptide, NSC-630176\], entinostat \[MS 275\], dacinostat \[LAQ-824\], belinostat \[(PXD-101\]), panobinostat \[LBH589\], mocetinostat \[MGCD0103\], CRA024781, etc); patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g., valproic acid for epilepsy, may enroll after a 30-day washout period
• Patient has known hypersensitivity to the components of study drug or its analogs or paclitaxel
• NYHA Class III or IV congestive heart failure, myocardial infarction within the previous 6 months, QTc \> 0.47 seconds, or uncontrolled arrhythmia
• Patient is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study
• Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled; patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for \> 5 years or are considered by their physician to be at less than 30% risk of relapse
• Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Vorinostat; Paclitaxel; Taxes; Radiotherapy; Radiation

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)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Shilpen Patel
• Organization: Departments of Radiation Oncology and Global Health University of Washington Medical Center

shilpenp@uw.edu

206-598-4100

Study Officials

• Shilpen Patel

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 18, 2008
• First Posted: April 21, 2008
• Study Start: March 1, 2008
• Primary Completion: January 1, 2010
• Study Completion: September 1, 2011
• Last Updated: June 14, 2017
• Results First Posted: June 14, 2017

Record last verified: 2017-05

Locations

US (1)