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Stage III Squamous Cell Carcinoma of the OropharynxPhase 1NCT01064921

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

A Phase 1 study testing vorinostat, cisplatin and radiation therapy in people with Stage III Squamous Cell Carcinoma of the Oropharynx and Stage IV Squamous Cell Carcinoma of the Oropharynx, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
vorinostat, cisplatin and radiation therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
19 Jan 2010to 8 Nov 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Mg levels preferred normal limits with no clinical abnormalities
  • Creatinine =< ULN OR Calculated creatinine clearance >= 50 mL/min
  • Serum total bilirubin =< 1.5 X ULN
  • AST (SGOT) and ALT (SGPT) =< 2.5 X ULN
  • Alkaline Phosphatase =< 2.5 X ULN
  • No known malabsorption syndrome
  • Female patients of childbearing potential must be willing to use birth control; the 2 birth control methods can be either 2 barrier methods or a barrier method plus a hormonal method to prevent pregnancy, used throughout the study starting with visit 1
  • The following are considered adequate barrier methods of contraception: diaphragm, condom (by the partner) or sponge; other methods of contraception such as copper intrauterine device or spermicide may be used
  • Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents); female patient of childbearing potential has a negative serum pregnancy test β-hCG within 7 days prior to receiving the first dose of vorinostat
  • Male patients agree to use an adequate method of contraception for the duration of the study
  • The patient must have a life expectancy of at least 12 weeks
  • Patients on coumadin therapy are eligible for study

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase I Trial Of Vorinostat In The Treatment Of Advanced Laryngeal, Hypopharyngeal, Nasopharyngeal And Oropharyngeal Squamous Cell Carcinoma Of The Head And Neck.

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximally tolerated dose of Vorinostat in combination with concurrent chemoradiotherapy for the treatment of advance stage OPSCC.

SECONDARY OBJECTIVES:

  1. To determine the complete response rate, overall survival and progression free survival using the maximally tolerated dose of Vorinostat.

TERTIARY OBJECTIVES:

  1. To assess treatment related acute and late toxicities when combining Vorinostat with chemoradiation and correlate these toxicities to molecular markers of apoptosis in tumor and normal oral mucosa.

II. To evaluate the effect of Vorinostat on tumor immune surveillance, particularly in HPV positive patients.

III. To illustrate that Vorinostat alters the methylation status of commonly methylated genes in OPSCC.

OUTLINE: This is a dose-escalation study of vorinostat. Patients receive oral vorinostat on days 0-2 and cisplatin IV on days 7, 21, and 35. Patients undergo radiotherapy 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). Treatment continues for 7 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Being tested
vorinostat, cisplatin, radiation therapy, Correlative Studies
Keywords
oropharyngeal cancer, recurrent squamous cell carcinoma of the oropharynx
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Oropharyngeal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • vorinostatDrug

    Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

    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).

  • cisplatinDrug

    Also called CACP, CDDP, CPDD, DDP

    Given IV

  • radiation therapyRadiation

    Also called irradiation, radiotherapy, therapy, radiation

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

  • Correlative StudiesProcedure or surgery

    Also called blood draw, biopsy

    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.

Study groups in NCT01064921
Study groupRoleWhat they receive
Arm IExperimentalPatients 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.
Receives: Drug: vorinostat; Drug: cisplatin; Radiation: radiation therapy; Procedure: Correlative Studies

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose of vorinostat in combination with concurrent chemoradiation therapy

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

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

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

Secondary outcomes (6)

  1. Tumor responses to vorinostat or vorinostat combined with chemoradiation.

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

  2. Complete response rate

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

  3. Overall survival

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

  4. Progression free survival

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

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

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

  6. HPV-specific T-cell in patients with HPV+ tumors

    Measured: After the run in period of vorinostat but before the start of RT; Day 35; 2 weeks after the completion of RT; Day 153

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Feb 2010 (estimated)
  2. Study start19 Jan 2010
  3. Primary completion8 Nov 2017
  4. Study completion8 Nov 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01064921
Sponsor's protocol ID
OSU-09120
Other IDs
NCI-2009-01606
Status last verified
Jun 2019
First submitted
5 Feb 2010
Last updated
4 Jun 2019
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing vorinostat, cisplatin and radiation therapy in people with Stage III Squamous Cell Carcinoma of the Oropharynx and Stage IV Squamous Cell Carcinoma of the Oropharynx, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose of vorinostat in combination with concurrent chemoradiation therapy (time frame: Weekly during treatment; Every 2 weeks for the first month after treatment completion; Then every 4 weeks until day 153). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01064921.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2019.

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