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Head and Neck CancerPhase 1/2NCT00573989

Intensity-Modulated Radiation Therapy, Pemetrexed, and Erlotinib in Treating Patients With Recurrent or Second Primary Head and Neck Cancer

A Phase 1/2 study testing erlotinib hydrochloride, pemetrexed disodium and quality-of-life assessment in people with Head and Neck Cancer, run by Wake Forest University Health Sciences at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs, such as pemetrexed and erlotinib, may make tumor cells more sensitive to radiation therapy. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Head and Neck Cancer
What is being tested?
erlotinib hydrochloride, pemetrexed disodium and quality-of-life assessment
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
2 sitesUnited States
Study dates
Mar 2008to Mar 2017
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed diagnosis of recurrent or second primary squamous cell carcinoma (SCC) of the head and neck, including any of the following:
  • Oral cavity
  • Oropharynx
  • Hypopharynx
  • Larynx
  • Recurrent neck metastases with unknown primary
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  • Exception from pathology confirmation of tumor recurrence is accepted for patients who originally had pathologically confirmed SCC of the Head and Neck, the new tumor is located in the head and neck area and it is clinically considered as a recurrence of the original tumor, and a tumor biopsy is technically difficult and would expose the patient to unjustified risk. The treating physicians should agree and document the clinical definition of tumor recurrence and should document the increased risk for biopsy.
  • Measurable disease by CT scan or MRI OR evaluable disease
  • No definitive evidence of distant metastasis
  • Unresectable disease by a preliminary ENT evaluation OR refused surgery
  • Patients may have received chemotherapy as a component of their primary tumor treatment but not for recurrent or metastatic disease. No prior treatment with systemic anti-EGFR inhibitors or Pemetrexed is permitted
  • Has undergone prior head and neck radiotherapy (for SCC of the head and neck) to a dose of ≤ 72 Gy that involved most of the recurrent tumor (> 75%) OR has a second primary tumor volume in areas previously irradiated to > 45 Gy
  • The entire tumor volume must be included in a treatment field that limits the total spinal cord dose to 54 Gy (prior plus planned dose)
  • Must have disease recurrence or persistence for ≥ 6 months after completion of prior radiotherapy
  • ECOG performance status 0-1
  • Age ≥ 18 years
  • ANC > 1,500/µL
  • Platelet count > 100,000/µL
  • Total bilirubin < 1.5 times upper limit of normal (ULN)
  • AST/ALT < 2 times ULN
  • Creatinine < 1.5 times ULN
  • Willing and able to take folic acid and vitamin B12 supplementation
  • Recovered from prior surgery, chemotherapy, or radiotherapy
  • At least 6 months since prior radiotherapy
  • At least 5 days since prior aspirin or other non-steroidal anti-inflammatory agents (8 days for long acting agents [e.g., piroxicam])
  • Fertile patients must use effective contraception

Who cannot join

  • Nasopharyngeal carcinoma
  • Concurrent uncontrolled illness, including, but not limited to, any of the following:
  • Ongoing or active infection
  • Psychiatric illness or social situation that would limit compliance with study requirements
  • Significant history of uncontrolled cardiac disease (i.e., uncontrolled hypertension; unstable angina; recent myocardial infarction [within the past 3 months]; uncontrolled congestive heart failure; or cardiomyopathy with decreased ejection fraction)
  • Active interstitial lung disease
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  • Presence of third space fluid that cannot be controlled by drainage
  • Other concurrent investigational agents
  • Pregnant or nursing
  • HIV positive

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • UNC Linberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Wake Forest University Comprehensive Cancer Center

    Winston-Salem, North Carolina, 27157-1096

Other trials in United States

About this study

Official title: Phase I/II Clinical Trial of Combined Pre-Irradiation With Pemetrexed and Erlotinib Followed by Maintenance Erlotinib for Recurrent and Second Primary Squamous Cell Carcinoma of the Head and Neck

RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs, such as pemetrexed and erlotinib, may make tumor cells more sensitive to radiation therapy. Erlotinib and pemetrexed may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving intensity-modulated radiation therapy together with pemetrexed and erlotinib may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with intensity-modulated radiation therapy and pemetrexed and to see how well they work in treating patients with recurrent or second primary head and neck cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Evaluate the acute toxicity and feasibility of intensity modulated radiotherapy (IMRT) in combination with radiosensitizing drugs pemetrexed disodium and erlotinib hydrochloride in patients with recurrent or second primary squamous cell carcinoma of the head and neck. (Phase I)
  • Determine the maximum tolerated dose and recommended phase II dose of erlotinib hydrochloride in these patients. (Phase I)
  • Determine progression-free survival (PFS) at 1 year in these patients. (Phase II)

Secondary

  • Determine median PFS, median overall survival (OS), and OS at 1 and 2 years in these patients.
  • Determine objective tumor response as measured by CT scan or MRI in these patients.
  • Evaluate the acute and chronic toxicity of IMRT in combination with radiosensitizing drugs pemetrexed disodium and erlotinib hydrochloride in these patients.
  • Evaluate the impact of treatment on quality of life as measured by FACT-H\&N, PSS-HN, MD Anderson Dysphagia Inventory (MDADI), and swallowing by direct functional measurements at different time points.
  • Evaluate the level of phosphorylation of different tyrosine residues within the cytoplasmic domain of EGFR, bound adaptors, as well as markers of downstream pathways activation by nano LC-MS/MS in tumor tissue and correlate with levels of P-AKT and P-ERK by immunohistochemistry and with response to treatment.
  • Measure the levels of TS and p53 and correlate with treatment response.

OUTLINE: This is a phase I, dose-escalation study of erlotinib hydrochloride followed by a phase II study.

  • Phase I: Patients undergo intensity modulated radiotherapy (IMRT) once daily, 5 days a week, for 6 weeks. Patients receive pemetrexed disodium IV over 10 minutes on day 1 of radiotherapy. Treatment with pemetrexed disodium repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral erlotinib hydrochloride once daily beginning on day 1 of radiotherapy and continuing for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Phase II: Patients undergo IMRT and receive pemetrexed sodium as in phase I. Patients also receive erlotinib hydrochloride at the maximum tolerated dose determined in phase I.

Quality of life is assessed at baseline, weekly during treatment, at 1, 6, and 12 months, and then annually thereafter.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 1 year, and then annually thereafter.

Being tested
erlotinib hydrochloride, pemetrexed disodium, quality-of-life assessment, intensity-modulated radiation therapy
Keywords
recurrent squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the larynx, recurrent verrucous carcinoma of the larynx, recurrent squamous cell carcinoma of the lip and oral cavity, recurrent verrucous carcinoma of the oral cavity, metastatic squamous neck cancer with occult primary squamous cell carcinoma, recurrent metastatic squamous neck cancer with occult primary, recurrent squamous cell carcinoma of the oropharynx
Medical subject headings
Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck

What participants receive

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

  • erlotinib hydrochlorideDrug

  • pemetrexed disodiumDrug

  • quality-of-life assessmentProcedure or surgery

  • intensity-modulated radiation therapyRadiation

Study groups in NCT00573989
Study groupRoleWhat they receive
ErlotinibExperimentalErlotinib
Receives: Drug: erlotinib hydrochloride; Drug: pemetrexed disodium; Procedure: quality-of-life assessment; Radiation: intensity-modulated radiation therapy

What is being measured

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

  1. Maximum Tolerated Dose of Erlotinib Hydrochloride (Phase I)

    Dose at which 100% of participants tolerated the dose

    Measured: 56 Days

  2. Progression-free Survival (PFS) at 1 Year (Phase II)

    Determine Progression Free Survival at 1 year defined as the percentage of patients who are alive at 1 year after beginning of their concurrent re-irradiation and chemotherapy without loco-regional progression of their disease as measured by CT scan or MRI.

    Measured: 1 year

Secondary outcomes (9)

  1. Median Progression Free Survival

    Median Progression Free Survival of participants reported after 2 years.

    Measured: 2 years

  2. Median Overall Survival

    Median Overall Survival of participants reported after 2 years.

    Measured: up to 5 years

  3. Overall Survival

    Overall survival of participants reported after 2 years.

    Measured: 1 and 2 years

  4. Evaluation of Acute and Chronic Toxicity

    Evaluate acute and chronic toxicity of the combined re-irradiation with radiosensitizing drugs: Pemetrexed and Erlotinib. Adverse events with Common Toxicity Criteria grades of 4 and 5 are reported for phase I and II.

    Measured: 1 year

  5. Change in Quality of Life- FACT H&N

    The Functional Assessment of Cancer Therapy-Head and Neck (FACT H\&N) consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for head and neck related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain. Score range is 0-156. Higher scores denotes better outcomes

    Measured: baseline and 12 months

  6. Change in Quality of Life: PSS-HN

    The Performance Status Scale for Head \& Neck Cancer Patients (PSS-HN) is s designed to evaluate performance in areas of functioning most likely affected by head and neck cancer and its treatment, specifically Normalcy of Diet, Eating in Public, and Understandability of Speech. Each subscale is rated from 0 to 100, with higher scores indicating better performance

    Measured: baseline and 6 months

  7. Change in Quality of Life: MDADI

    The M.D. Anderson Dysphagia Inventory (MDADI) was used to assess effects of dysphagia on the quality of life of patients with head and neck cancer. It incorporates 3 domains (emotional, functional, and physical) as well as 1 global question. Each subscale with five possible responses scored on a scale of 1 to 5 (strongly agree, agree, no opinion, disagree and strongly disagree). Scores range from 0 (extremely low functioning) to 100 (higher functioning). Higher MDADI score represents better day-to-day functioning and better quality of life.

    Measured: baseline and 12 months

  8. Evaluation of Biomarkers

    Measured: throughout study completion, up to 2 years

  9. Objective Tumor Response

    Objective Tumor Response reported on participants at 1 year (complete, partial, progression, or stable response).

    Measured: 1 year

Timeline

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

  1. First posted14 Dec 2007 (estimated)
  2. Study startMar 2008
  3. Primary completionMar 2017
  4. Study completionMar 2017

Why it stopped: Drug Supply Issue

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 1/2
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
NCT00573989
Sponsor's protocol ID
IRB00003457
Other IDs
P30CA012197, CCCWFU-60107
Status last verified
Dec 2018
First submitted
13 Dec 2007
Last updated
3 Jan 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing erlotinib hydrochloride, pemetrexed disodium and quality-of-life assessment in people with Head and Neck Cancer, run by Wake Forest University Health Sciences at 2 sites 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 26 inclusion and 10 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: stopped early, as of the sponsor's last update on 3 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Erlotinib Hydrochloride (Phase I) (time frame: 56 Days). 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 NCT00573989.

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 3 Jan 2019.

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