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A Phase II Study of Vorinostat and Capecitabine in Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN) and Nasopharyngeal Carcinoma (NPC)


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Recurrent Verrucous Carcinoma of the Larynx, Recurrent Verrucous Carcinoma of the Oral Cavity, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Larynx, Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Oropharynx, Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IV Verrucous Carcinoma of the Larynx, Stage IV Verrucous Carcinoma of the Oral Cavity, Tongue Cancer

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Trial Information

A Phase II Study of Vorinostat and Capecitabine in Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN) and Nasopharyngeal Carcinoma (NPC)


PRIMARY OBJECTIVES:

I. To determine the objective response rate (complete and partial) and duration of response
of the combination of vorinostat and capecitabine in patients with recurrent and/or
metastatic SCCHN.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of the combination of vorinostat and capecitabine
in patients with recurrent and/or metastatic SCCHN.

II. To determine the rate of progression-free survival (PFS) at 6 months. III. To determine
the rate and duration of stable disease (SD). IV. To determine the median PFS, and the rate
of PFS at 1 year. V. To determine the median overall survival (OS), and rates of overall
survival at 6 months and at 1 year.

OUTLINE: This is a multicenter, open-label study of patients with squamous cell carcinoma of
the head and neck followed by a randomized study of patients with nasopharyngeal carcinoma
(NPC).

Patients receive oral capecitabine twice daily and oral vorinostat once daily on days 1-14.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients with complete response may receive two additional courses. Patients with NPC are
randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral capecitabine twice daily on days 1-14.

ARM II: Patients receive oral vorinostat once daily and capecitabine as in arm I on days
1-14.

In both arms, courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity.

After completion of study therapy, patients will be followed up every 6 months for 1 year.


Inclusion Criteria:



- Histologically or cytologically confirmed disease meeting 1 of the following
criteria:

- Squamous cell carcinoma of the head and neck (SCCHN)

- Oral cavity

- Oropharynx

- Larynx

- Hypopharynx

- Paranasal sinus

- SCCHN of unknown origin must be reviewed and approved by principal
investigator

- Nasopharyngeal carcinoma (NPC)

- 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 enrolment; patients are eligible if
they received 5-FU as part of the initial multimodality treatment; patients are not
eligible if they received capecitabine previously

- Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1
dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or
as ≥ 10 mm by spiral CT scan

- Indicator lesions must not have been previously treated with surgery,
radiotherapy, or radio frequency ablation unless there is documented progression
after therapy

- No known brain metastases

- ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)

- Life expectancy > 12 weeks

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin ≤ 1.25 times upper limit of normal (ULN)

- AST and ALT ≤ 3 times ULN (≤ 5 times ULN for patients with documented liver
metastases)

- Creatinine ≤ 1.25 times ULN OR creatinine clearance ≥ 50 mL/min

- ECG with normal tracing or non-clinically significant changes that do not require
medical intervention

- QTc interval < 470 msec and without history of Torsade de Pointes or other
symptomatic QTc abnormality

- Not pregnant or nursing

- Fertile patients must use effective contraception (abstinence or 2 birth control
methods) prior to and for the duration of study

- Willing and able to comply with schedule visits, treatment plan, laboratory tests,
and other study procedures

- More than 5 years since another malignancy except stage 0-IB cervical carcinoma,
non-invasive basal cell or squamous cell skin carcinoma, or radically treated
prostate cancer (prostatectomy or radiotherapy) with normal PSA and not requiring
ongoing anti-androgen hormonal therapy

- More than 10 years since malignant melanoma

- No inability to take oral medications and/or a clinical or radiological diagnosis of
bowel obstruction

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to vorinostat or other agents used in this study

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Active peptic ulcer disease

- Myocardial infarction within the past 6 months

- Congestive heart failure

- Symptomatic congestive heart failure

- Active cardiomyopathy

- Unstable angina pectoris

- Cardiac arrhythmia

- Uncontrolled hypertension

- Psychiatric illness and/or social situations that would limit compliance with
study requirements

- Not HIV positive

- No known dihydropyrimidine dehydrogenase (DPD) deficiency

- No concurrent radiotherapy (except for metastatic bone lesions)

- At least 4 weeks since prior targeted therapy for recurrent or metastatic squamous
cell carcinoma of the head and neck (SCCHN)

- No prior or other concurrent histone deacetylase (HDAC) inhibitors (e.g.,
valproic acid)

- More than 6 months since prior systemic chemotherapy (i.e., induction, concurrent,
or adjuvant) as part of the initial multimodality treatment for locally advanced
disease

- No prior fluorouracil as part of initial modality treatment for patients with
SCCHN

- Prior fluorouracil for patients with nasopharyngeal carcinoma (NPC) allowed

- No prior capecitabine for patients with SCCHN or NPC

- At least 4 weeks since prior surgery or radiotherapy

- Concurrent medication or substances known to affect or with the potential to affect
the activity of vorinostat will be reviewed in a case by case by principal
investigators

- No other concurrent investigational agents

- No concurrent medications that are generally accepted to have risk of causing
Torsades de Pointes

- No other concurrent anticancer therapy

- Palliative interventions, such as paracentesis or palliative surgery, allowed

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rate (complete and partial response) according to RECIST (Cohort A)

Outcome Description:

95% confidence intervals will be provided for all interesting results.

Outcome Time Frame:

Up to 1 year

Safety Issue:

No

Principal Investigator

Eric Chen

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Health Network-Princess Margaret Hospital

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02556

NCT ID:

NCT01267240

Start Date:

December 2010

Completion Date:

Related Keywords:

  • Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
  • Recurrent Metastatic Squamous Neck Cancer With Occult Primary
  • Recurrent Squamous Cell Carcinoma of the Hypopharynx
  • Recurrent Squamous Cell Carcinoma of the Larynx
  • Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Recurrent Squamous Cell Carcinoma of the Nasopharynx
  • Recurrent Squamous Cell Carcinoma of the Oropharynx
  • Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Recurrent Verrucous Carcinoma of the Larynx
  • Recurrent Verrucous Carcinoma of the Oral Cavity
  • Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IV Squamous Cell Carcinoma of the Hypopharynx
  • Stage IV Squamous Cell Carcinoma of the Larynx
  • Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IV Squamous Cell Carcinoma of the Nasopharynx
  • Stage IV Squamous Cell Carcinoma of the Oropharynx
  • Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IV Verrucous Carcinoma of the Larynx
  • Stage IV Verrucous Carcinoma of the Oral Cavity
  • Tongue Cancer
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms
  • Laryngeal Diseases
  • Tongue Neoplasms
  • Carcinoma, Verrucous
  • Neoplasms, Unknown Primary
  • Hypopharyngeal Neoplasms
  • Laryngeal Neoplasms
  • Paranasal Sinus Neoplasms
  • Oropharyngeal Neoplasms
  • Nasopharyngeal Neoplasms

Name

Location

City of Hope Comprehensive Cancer CenterDuarte, California  91010
University of PittsburghPittsburgh, Pennsylvania  15261
Contra Costa Regional Medical CenterMartinez, California  94553-3156
Tower Cancer Research FoundationBeverly Hills, California  90211
UC Davis Comprehensive Cancer CenterSacramento, California  95817
University of Southern CaliforniaLos Angeles, California  90033
Penn State Milton S Hershey Medical CenterHershey, Pennsylvania  17033
City of Hope Medical Group IncPasadena, California  91105
Veterans Administration Hospital - MartinezMartinez, California  94553