Ph I Vorinostat in the Treatment of Advanced Staged Oropharyngeal Squamous Cell Carcinoma

NCT01064921 | Completed Phase 1 DMC

• 2 other identifiers: OSU-09120NCI-2009-01606
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, 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 and other types of radiation to kill tumor cells. Giving vorinostat together with chemotherapy and radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with cisplatin and radiation therapy in treating patients with stage III or stage IVa squamous cell cancer of the oropharynx which is either unresectable or borderline resectable.

Conditions

Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx

Keywords

oropharyngeal cancer; recurrent squamous cell carcinoma of the oropharynx

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of vorinostat in combination with concurrent chemoradiation therapy

  Weekly during treatment; Every 2 weeks for the first month after treatment completion; Then every 4 weeks until day 153

• The toxic effects of the combination of vorinostat and cisplatin using NCI CTCAE v. 4.0

  Weekly during treatment; Every 2 weeks for the first month after treatment completion; Then every 4 weeks until day 153

Secondary Outcomes (6)

• Tumor responses to vorinostat or vorinostat combined with chemoradiation.

  Days 35, 56 then after Day 153 every 12 weeks for 24 months

• Complete response rate

  Days 35, 56 then after Day 153 every 12 weeks for 24 months

• Overall survival

  Days 35, 56 then after Day 153 every 12 weeks for 24 months

• Progression free survival

  Days 35, 56 then after Day 153 every 12 weeks for 24 months

• Relationship between Vorinostat therapy and tumor suppressor genes product assessed by Fas and FasL protein expression level in tumor and the normal mucosa

  Before, post SAHA treatment, and post the concurrent chemoradiation /SAHA therapy

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive oral vorinostat on days 0-2 and cisplatin IV on days 7, 21 and 35. Patients undergo radiation therapy 5 days a week beginning on day 7. Patients also receive concurrent oral vorinostat along with the radiotherapy to be given 3 days per week (Monday, Tuesday, and Wednesday). Optional repeat tumor and normal mucosal biopsies will be performed and blood will be drawn for correlative studies.

Drug: vorinostat; Drug: cisplatin; Radiation: radiation therapy; Procedure: Correlative Studies

Interventions

vorinostat DRUG

The first vorinostat dose level is 100mg, and the second dose will be 200mg, third dose will be 300mg. If the first vorinostat dose level is found to be excessively toxic, the patient will be reduced to -1 dosing level then if still too toxic reduced again to dose level -2. Dose escalation of vorinostat will continue in increments of 100 mg (i.e., 200 mg on dosing days, 300 mg on dosing days). Vorinostat will be given 3 consecutive days per week (e.g. Monday, Tuesday, Wednesday).

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

Arm I

cisplatin DRUG

Given IV

Also known as: CACP, CDDP, CPDD, DDP, Neoplatin, PDD

Arm I

radiation therapy RADIATION

Standard chemoradiation therapy X 7 weeks (Days 7-56), concurrent with oral Vorinostat given three days per week (Mon, Tues, Wed)

Also known as: irradiation, radiotherapy, therapy, radiation

Arm I

Correlative Studies PROCEDURE

Day 35, 2 weeks post radiation therapy completion optional tumor/normal muscosal biopsy and blood draw for correlative studies. At day 153 an optional tumor/normal tissue biopsy and blood draw for correlative studies.

Also known as: blood draw, biopsy

Arm I

Eligibility Criteria

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

You may qualify if:

• Patients with histologically confirmed unresectable or borderline resectable squamous cell carcinoma of the oropharynx will be eligible for enrollment to the clinical trial
• Oropharyngeal sites of tumor include tonsil, soft palate, base of tongue, lateral and posterior pharyngeal wall
• Patient must be AJCC (American Joint Committee on Cancer) Stage III (T3N0, T1-2N1) or Stage IVa (T1-4N2-3M0, T4N0-1 M0) and be either unresectable or borderline resectable
• No prior therapy for the tumor, including extensive surgery, radiation therapy, chemotherapy, immunotherapy, targeted therapy or any other investigational agents; surgical biopsy prior to beginning the study is allowable
• Prior malignancies at sites other than the head and neck are allowable if there has been greater than or equal to a 3 year disease free interval; basal cell carcinoma of the skin and in-situ cervix dysplasias are allowable within this 3 year interval if completely resected
• There must be documentation of evaluable tumor within four weeks of beginning therapy
• ECOG (Eastern Cooperative Oncology Group) Performance Status 0-2, (Karnofsky \> 60%)
• Ability to understand and the willingness to sign a written informed consent
• Patient must have normal liver and bone marrow function
• Absolute neutrophil count (ANC) \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL
• Prothrombin Time or INR (international normalized ratio) =\< 1.5x upper limit of normal (ULN) unless receiving therapeutic anticoagulation
• Partial thromboplastin time (PTT) =\< 1.2 times the ULN unless the patient is receiving therapeutic anticoagulation
• K levels preferred normal limits with no clinical abnormalities

You may not qualify if:

• Major surgery or trauma occurring within 28 days of starting the trial
• History of allergic reactions attributed to compounds similar in chemical or biological composition to Vorinostat or other agents used in this study
• Gastrointestinal tract disease or previous surgical procedures resulting in an inability to take oral or enteral medication or a requirement for IV alimentation
• Pregnant women; breast feeding should be discontinued during treatment
• Active peptic ulcer disease
• Uncontrolled comorbid illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina, untreated or new cardiac arrhythmia, psychiatric or social condition which would limit the patient's understanding of and compliance with the study
• Prisoners and other vulnerable populations
• Patients who have had prior treatment with an HDAC inhibitor (e.g., romidepsin (Depsipeptide), NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589, 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 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)
• Patients with known active viral hepatitis or known HIV infection

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (1)

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• Jamesline

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms

Interventions

Vorinostat; Cisplatin; Radiotherapy; Radiation; Blood Specimen Collection; Biopsy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics; Physical Phenomena; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical

Study Officials

• Old Matthew, MD

  Ohio State University

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 5, 2010
• First Posted: February 9, 2010
• Study Start: January 19, 2010
• Primary Completion: November 8, 2017
• Study Completion: November 8, 2017
• Last Updated: June 4, 2019

Record last verified: 2019-06

Locations

US (1)