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Head and Neck CancerPhase 1NCT01540682

MLN8237 in Head and Neck Cancer

A Phase 1 study testing MLN8237, Cetuximab and Radiotherapy in people with Head and Neck Cancer, run by Abramson Cancer Center at Penn Medicine 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

This study will evaluate the initial safety and effectiveness of an investigational drug, MLN8237, added to routine radiation therapy and cetuximab in patients with head and neck cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Cancer
What is being tested?
MLN8237, Cetuximab and Radiotherapy
Type of treatment
Surgery or procedure
How many people
9 participants
Where
1 siteUnited States
Study dates
Feb 2012to Nov 2015
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

  • Male or females greater than 18 years of age.
  • ECOG performance status of 0-1
  • Patients must have histologically or cytologically confirmed HNSCC of the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx or paranasal sinuses that is considered after a multidisciplinary evaluation (surgery, medical oncology \& radiation oncology) to be appropriate for definitive cetuximab-based radiation therapy
  • No distant metastatic disease. Minimum work-up includes:
  • History/physical examination within 4 weeks prior to registration, including assessment of weight and weight loss in past 6 months and an examination by a Medical Oncologist
  • PET/CT scan within 6 weeks prior to registration
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  • CT scan or MRI of the head and neck (of the primary tumor and neck nodes) within 4 weeks prior to registration
  • Adequate organ and marrow function
  • Negative pregnancy test within 2 weeks prior to registration for women of childbearing potential. The effects of MLN8237 on the developing human fetus are unknown. For this reason and because MLN8237 agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Male subject agrees to use an acceptable method for contraception during the entire study treatment period through 4 months after the last dose of MLN8237.
  • Ability to understand and willingness to sign a written informed consent document with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Who cannot join

  • Systemic anti-neoplastic treatment within 21 days preceding the first dose of MLN8237. Patients treated with non-cytotoxic small molecule drugs (eg, tyrosine kinase inhibitors, such as erlotinib and hormonal agents, such as letrozole) must not have received treatment with these drugs for at least 2 weeks before the first dose of MLN8237 is administered.
  • Patient has already had definitive surgical treatment, excluding diagnostic biopsy of the primary site or nodal sampling of neck disease. Prior radical or modified neck dissection is also not permitted.
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
  • Primary tumor site is skin or salivary gland.
  • Uncorrected CTCAE, v. 4.0 grade 3-4 electrolyte abnormalities
  • Patients may not be receiving any other investigational agents or treatment with any investigational products within 21 days before the first dose of study drug.
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  • Patients with known brain metastasis are excluded from this clinical trial because of their poor prognosis and because they often develop rapid progressive neurologic dysfunction that would confound the evaluation of neurological and other adverse events.
  • History of known allergic reactions attributed to compounds of similar chemical or biologic composition to MLN8237 or cetuximab.
  • Patients may not be taking proton pump inhibitors, H2 antagonists or pancreatic enzyme replacement. Subjects who refuse to limit use of alcohol are also excluded.
  • Severe, active co-morbidity
  • Clinical evidence of intestinal malabsorption. Examples include resection of pancreas or upper small bowel, requirement for pancreatic enzymes, or any other condition that would modify small bowel absorption of oral medications.
  • Prior treatment with high-dose chemotherapy, defined as chemotherapy requiring the use of peripheral blood or bone marrow stem cell support for hematopoietic reconstitution, including prior allogeneic bone marrow transplantation.
  • Prior radiotherapy to greater or equal to 25% of bone marrow. Whole pelvic radiation is considered to be over 25%.
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
  • Major surgery within 14 days prior to the first dose of study drug treatment.
  • Inability to swallow oral medication or to maintain a fast as required 2 hours before and 1 hour after MLN8237 administration.
  • Known history of HIV infection, or active hepatitis B, or hepatitis C infection. Testing is NOT required in the absence of clinical findings or suspicion.
  • Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.
  • Patient has Grade 2 or higher peripheral neuropathy within 14 days before enrollment.
  • Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum -human chorionic gonadotropin (-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  • Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days prior to the first dose of MLN8237 and during the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Abramson Cancer Center of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: Phase I Study of MLN8237 in Combination With Cetuximab and Definitive Radiation in Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

This study will evaluate the initial safety and effectiveness of an investigational drug, MLN8237, added to routine radiation therapy and cetuximab in patients with head and neck cancer. This study will also determine the highest dose of MLN8237 that can be given together with cetuximab and radiation therapy without causing severe side effects.

Read the detailed description

This is a phase 1b study of MLN8237, cetuximab and definitive radiation therapy for patients with previously untreated locoregionally advanced HNSCC who are candidates for definitive radiation therapy with curative intent with cetuximab as the radiosensitizer. The treatment regimen consists of MLN8237 po bid for 7 days followed by 2 weeks off for 4 cycles with the first 3 cycles of MLN8237 concurrent with RT. Three dose levels of MLN8237 are planned: 30, 40 and 50 mg po bid. Cetuximab will be given at the FDA-approved loading and maintenance doses starting ~ 1 week prior to the initiation of radiation therapy and continuing for a grand total of 12 weeks. Radiotherapy will be administered in 2-Gy fractions, 5 days a week, to total dose of ~70 Gy according to standard departmental protocols. Correlative biomarker assays on pre- and on-therapy biopsy specimens (tissue micro arrays analyzed by AQUA quantitative immunofluorescence) will seek to establish proof-of-mechanism by determining if the novel drug combination has the predicted effects on biochemical signaling pathways linked to Aurora A and EGFR. Tumor samples will also be analyzed for Aurora A and EGFR expression by IHC and FISH.

Being tested
MLN8237, Cetuximab, Radiotherapy
Keywords
Male and female patients with HNSCC of the oral cavity, oropharynx, hypopharynx, larynx,, nasopharynx or paranasal sinuses that is considered appropriate, for definitive cetuximab-based radiation therapy.
Medical subject headings
Head and Neck Neoplasms, Laryngeal Diseases

What participants receive

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

  • MLN8237Drug

    Three dose levels of MLN8237 are planned:30, 40 and 50 mg po bid.

  • CetuximabDrug

    ~ 1 week prior to the initiation of radiation therapy and continuing for a grand total of 12 weeks.

  • RadiotherapyRadiation

    Radiotherapy will be administered in 2-Gy fractions, 5 days a week to a total dose of ~70 Gy.

What is being measured

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

  1. Number of Adverse Events

Timeline

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

  1. First posted29 Feb 2012 (estimated)
  2. Study startFeb 2012
  3. Primary completionNov 2015

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
Enrolment
9 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01540682
Sponsor's protocol ID
UPCC 10311
Status last verified
Aug 2018
First submitted
9 Feb 2012
Last updated
29 Aug 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MLN8237, Cetuximab and Radiotherapy in people with Head and Neck Cancer, run by Abramson Cancer Center at Penn Medicine 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 11 inclusion and 21 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 29 Aug 2018. 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?

Number of Adverse Events. 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 NCT01540682.

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 29 Aug 2018.

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