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)
Overview
- Phase
- Phase 2
- Intervention
- Capecitabine
- Conditions
- Paranasal Sinus Squamous Cell Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 25
- Locations
- 14
- Primary Endpoint
- Response Rate According to Response Evaluation Criteria in Solid Tumors
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
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.
Detailed Description
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 squamous cell carcinoma of the head and neck (SCCHN). (SCCHN) II. 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 nasopharyngeal carcinoma (NPC). (NPC) SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of the combination of vorinostat and capecitabine in patients with recurrent and/or metastatic SCCHN. (SCCHN) II. To determine the rate of progression-free survival (PFS) at 6 months. (SCCHN) III. To determine the rate and duration of stable disease (SD). (SCCHN) IV. To determine the median PFS, and the rate of PFS at 1 year. (SCCHN) V. To determine the median overall survival (OS), and rates of overall survival at 6 months and at 1 year. (SCCHN) VI. To evaluate the safety and tolerability of the combination of vorinostat and capecitabine in patients with recurrent and/or metastatic NPC. (NPC) VII. To determine the duration of objective response. (NPC) VIII. To determine the rate and duration of stable disease (SD). (NPC) IX. To determine the median PFS, and the rate of PFS at 1 year. (NPC) X. To determine the median overall survival (OS), and rates of overall survival at 6 months and at 1 year. (NPC) OUTLINE: This is a non-randomized, open-label study of patients with SCCHN and NPC (Stage I), followed by a randomized study of patients with NPC (Stage II). STAGE I: Patients receive capecitabine orally (PO) twice daily (BID) and vorinostat PO daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. STAGE II: Patients with NPC are randomized to 1 of 2 treatment arms. ARM I: 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. ARM II: Patients receive capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients will be followed up at 3-4 weeks and then every 6 months for 1 year.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Arm I (capecitabine, vorinostat)
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.
Intervention: Capecitabine
Arm I (capecitabine, vorinostat)
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.
Intervention: Vorinostat
Outcomes
Primary Outcomes
Response Rate According to Response Evaluation Criteria in Solid Tumors
Time Frame: Up to 1 year
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.
Secondary Outcomes
- Progression-free Survival(From time of treatment initiation to disease progression, death, or completion of the 1 year follow-up, whichever occurs first.)
- Survival(Up to 1 year)