Capecitabine and Vorinostat in Treating Patients With Recurrent and/or Metastatic Head and Neck Cancer

NCT01267240 | Terminated Phase 2 Results DMC

• 8 other identifiers: NCI-2011-02556PMH-PHL-068CDR0000689859NCI 8192PHL-0688192N01CM00032N01CM00038
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 14

Brief Summary

This partially randomized phase II trial studies giving capecitabine and vorinostat in treating patients with head and neck cancer that has come back after previous treatment or that has spread to other areas in the body. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving capecitabine together with vorinostat is more effective than capecitabine alone in treating patients with cancer of the head and neck cancer.

Conditions

Paranasal Sinus Squamous Cell Carcinoma; Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Oral Cavity Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Hypopharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Oral Cavity Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Response Rate According to Response Evaluation Criteria in Solid Tumors

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

  Up to 1 year

Secondary Outcomes (2)

• Survival

  Up to 1 year

• Progression-free Survival

  From time of treatment initiation to disease progression, death, or completion of the 1 year follow-up, whichever occurs first.

Study Arms (1)

Arm I (capecitabine, vorinostat)

EXPERIMENTAL

Patients receive capecitabine PO BID and vorinostat PO daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Capecitabine; Drug: Vorinostat

Interventions

Capecitabine DRUG

Given PO

Also known as: Ro 09-1978/000, Xeloda

Arm I (capecitabine, vorinostat)

Vorinostat DRUG

Given PO

Also known as: L-001079038, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza

Arm I (capecitabine, vorinostat)

Eligibility Criteria

• Age: 19 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 SCCHN or NPC that is recurrent and/or metastatic and that is not amendable to curative therapy by surgery or radiation; SCCHN originating from the following sites are eligible: oral cavity, oropharynx, larynx, hypopharynx and paranasal sinus are eligible; for patients with a diagnosis of SCCHN of unknown origin, their eligibility must be reviewed and approved by the principal investigator
• For patients with SCCHN, they may have received one prior targeted therapy for recurrent or metastatic disease (excluding histone deacetylase \[HDAC\] inhibitors) provided treatment is completed \> 4 weeks prior to enrollment; they may have received prior systemic chemotherapy (ie, induction, concurrent or adjuvant) for SCCHN as part of the initial multimodality treatment for locally advanced disease if the chemotherapy is completed \> 6 months prior to enrollment; patients are not eligible if they received fluorouracil (5-FU) or capecitabine previously as part of the initial multimodality treatment
• Patients with NPC must have completed one prior chemotherapy regimen for recurrent or metastatic disease at least 4 weeks prior to enrollment; in addition, they may have received prior systemic chemotherapy (ie, induction, concurrent or adjuvant) for NPC as part of the initial multimodality treatment for locally advanced disease if the chemotherapy is completed \> 6 months prior to enrollment; patients are eligible if they received 5-FU as part of the initial multimodality treatment; patients are not eligible if they received capecitabine previously
• 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) as \> 20 mm with conventional techniques or as \> 10 mm with spiral computed tomography (CT) scan; indicator lesions must not have been previously treated with surgery, radiation therapy or radiofrequency ablation unless there is documented progression after therapy
• Patients must have completed any previous surgery or radiotherapy \>= 4 weeks prior to enrollment
• Previously treated patients must have evidence of progressive disease, either clinically or radiographically, as assessed by the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky \> 60%)
• Life expectancy of greater than 12 weeks
• Absolute neutrophil count \>= 1.5 x 10\^9/L
• Platelets \>= 100 x 10\^9/L
• Total bilirubin =\< 1.25 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN or =\< 5 x ULN with documented liver metastases
• Creatinine =\< 1.25 x ULN OR creatinine clearance \>= 50 mL/min/1.73 m\^2 for patients with creatinine levels above 1.25 x ULN
• lead electrocardiogram (ECG) with normal tracing, or non-clinically significant changes that do not require medical intervention; corrected QT (QTc) interval \< 470 msec, and without history of Torsades de Pointes or other symptomatic QTc abnormality
• Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity of vorinostat will be determined following review of their case by the principal investigator

You may not qualify if:

• Past or current malignancy other than SCCHN or NPC, except for:
• Cervical carcinoma Stage 1B or less
• Non-invasive basal cell and squamous cell skin carcinoma
• Malignant melanoma with a complete response of a duration of \> 10 years
• Radically treated prostate cancer (prostatectomy or radiotherapy) with normal prostate specific antigen (PSA), and not requiring ongoing anti-androgen hormonal therapy
• Other cancer diagnosis with a complete response of duration of \> 5 years
• Patients may not be receiving any other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial
• Prior use of capecitabine is not allowed
• Prior and concomitant treatment with HDAC inhibitors (such as valproic acid) are not allowed
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or other agents used in study
• Patients who are unable to take oral medications and / or who have a clinical or radiological diagnosis of bowel obstruction are ineligible
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, active peptic ulcer disease, myocardial infarction within 6 months prior to entry, congestive heart failure, symptomatic congestive heart failure, active cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with vorinostat
• Human immunodeficiency virus (HIV)-positive patients are ineligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (14)

Tower Cancer Research Foundation

Beverly Hills, California, 90211-1850, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Contra Costa Regional Medical Center

Martinez, California, 94553-3156, United States

Location

Veterans Administration Hospital - Martinez

Martinez, California, 94553, 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

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

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

London Health Sciences Centre-Corporate

London, Ontario, N6A 4L6, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Capecitabine; Vorinostat

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Limitations and Caveats

Early termination due to lack of activity of study drug.

Results Point of Contact

• Title: Dr.Eric Chen, Principal Investigator
• Organization: Princess Margaret Cancer Centre

eric.chen@uhn.ca

416-946-4501

Study Officials

• Eric Chen

  University Health Network-Princess Margaret Hospital

  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: December 24, 2010
• First Posted: December 28, 2010
• Study Start: December 1, 2010
• Primary Completion: June 1, 2015
• Study Completion: October 1, 2016
• Last Updated: April 14, 2017
• Results First Posted: April 14, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5); US (9)