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Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7Phase 1NCT02381535

Onalespib in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin

A Phase 1 study testing Cisplatin, Intensity-Modulated Radiation Therapy and Laboratory Biomarker Analysis in people with Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7 and Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7, run by National Cancer Institute (NCI) at 2 sites in 2 countries.

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 phase I trial studies the side effects and best dose of onalespib when given together with intensity-modulated radiation therapy (IMRT) and cisplatin in treating patients with squamous cell carcinoma of the head and neck that has spread from where it started to nearby tissue or lymph nodes. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Cisplatin, Intensity-Modulated Radiation Therapy and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
2 sitesin 2 countries
Study dates
22 Oct 2015to 24 Apr 2020
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have a histologically or cytologically confirmed, previously untreated squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
  • Tumors must be staged T1-4, N2b-3, M0 (human papillomavirus positive [HPV]+ or HPV negative [-]); patients with HPV+ tumors should have at least one high risk feature such as T4, N3, or smoking history of > 10 pack years
  • The disease must be considered to be potentially curable by combined radiotherapy and cisplatin based chemotherapy
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Life expectancy of greater than 6 months
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
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  • Hemoglobin >= 9 g/dL
  • Platelets >= 100 x 10^9/L
  • Serum creatinine =< 1.5 mg/dL (=< 120 umol/L) OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min
  • Bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN
  • Alanine aminotransferase (ALT) =< 2.5 x ULN
  • Proteinuria =< +1 on dipstick or =< 1 gram/24 hours
  • Corrected QT using the Fridericia formula (QTcF) < 470 msec
  • 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, during the study participation, and for three months after the last dose of the drug; women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to registration and agree to use effective contraception throughout the treatment period and for 3 months after the last dose of study treatment; 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; men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception; males should avoid fathering children during and for at least three months after therapy is completed
  • Ability to understand and the willingness to sign a written informed consent document
  • Available for long-term follow-up of their disease after treatment

Who cannot join

  • Patients with nasopharyngeal, paranasal sinus, skin, or unknown primary site disease
  • Presence of distance metastases (M1)
  • History of another malignancy; exception: patients who have been disease-free for > 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible; consult the Cancer Therapy Evaluation Program (CTEP) Medical Monitor if unsure whether second malignancies meet the requirements specified above
  • Previous head and neck radiation therapy
  • Symptomatic peripheral neuropathy > grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) criteria
  • Clinically significant sensorineural hearing impairment which may be worsened via cisplatin exposure (audiometric abnormalities without corresponding clinical deafness are not grounds for exclusion)
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  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to AT13387
  • Current use of a prohibited medication; the following medications or non-drug therapies are prohibited: the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra [ma huang], ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng)
  • History or current evidence/risk of visual loss syndromes, including but not limited to retinal vein occlusion (RVO), retinal detachment, macular degeneration, or visual migraine headaches
  • History or evidence of cardiovascular risk including any of the following:
  • History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)
  • History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization
  • History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system
  • Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy
  • Patients with intra-cardiac defibrillators
  • Known hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible); patients with known human immunodeficiency virus (HIV) infection are eligible if not on antiviral agents and cluster of differentiation (CD)4 counts are adequate (>= 500)
  • HIV-positive patients on combination antiretroviral therapy are ineligible
  • Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Any condition or medical problem in addition to the underlying malignancy and organ dysfunction which the investigator feels would pose unacceptable risk
  • Breastfeeding patients are ineligible

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • Yale University

    New Haven, Connecticut, 06520

Other trials in United States

Canada1 site

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase I Trial of AT13387 in Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck (LA-SCCHN) Receiving Concurrent Radiation and Cisplatin

This phase I trial studies the side effects and best dose of onalespib when given together with intensity-modulated radiation therapy (IMRT) and cisplatin in treating patients with squamous cell carcinoma of the head and neck that has spread from where it started to nearby tissue or lymph nodes. Onalespib works by blocking a protein called HSP90. HSP90 helps protect cells from stress and supports many other proteins that cause cell growth. When HSP90 is blocked, tumor cell growth may be slowed or stopped and may die more easily when treated with chemotherapy and radiation. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. IMRT is a specialized radiation therapy that delivers beams of radiation of different intensities aimed at the tumor from many angles and may kill more tumor cells and cause less damage to normal tissue. Giving onalespib with cisplatin and IMRT may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety and recommended phase II dose (RP2D) of onalespib (AT13387) in combination with concurrent cisplatin and radiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). (Dose Escalation Phase) II. To preliminarily evaluate the safety and preliminary efficacy of AT13387 in combination with concurrent cisplatin and radiotherapy in patients with LA-SCCHN. (Dose Expansion Phase)

SECONDARY OBJECTIVES:

  1. To evaluate the pharmacokinetics of AT13387 in combination with cisplatin and radiotherapy.

II. To evaluate the pharmacokinetics of cisplatin in combination with AT13387 and radiotherapy.

III. To assess for pharmacodynamics biomarkers for proof-of-mechanism. IIV. To assess for potential predictive biomarkers of efficacy. V. To document the toxicities associated with the administration of AT13387 in combination with cisplatin and radiotherapy in patients with LA-SCCHN.

VI. To explore and characterize predictive biomarkers for individual cancer patients utilizing genomic sequencing technologies.

VII. To provide preliminary disease-free survival, locoregional control, distant metastases-free survival, and overall survival.

OUTLINE: This is a dose-escalation study of onalespib.

Patients receive onalespib intravenously (IV) over 1 hour on days -7, 3, 10, 24, 31, and 38 and cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, 36, and 43. Patients also undergo IMRT once daily (QD), 5 days a week over 7 weeks for a total of 35 fractions. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 8 weeks, every 3 months for 1 year, and then every 6 months for 1 year. Beyond the first 2 years, patients may be followed up every 6 months for up to 3 years per institutional standards.

Being tested
Cisplatin, Intensity-Modulated Radiation Therapy, Laboratory Biomarker Analysis, Onalespib, Pharmacological Study
Medical subject headings
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.

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy

    Undergo IMRT

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • OnalespibDrug

    Also called AT 13387, AT-13387, AT13387

    Given IV

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT02381535
Study groupRoleWhat they receive
Treatment (onalespib, cisplatin, IMRT)ExperimentalPatient receive onalespib IV over 1 hour on days -7, 3, 10, 24, 31, and 38 and cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, 36 and 43. Patients also undergo IMRT QD, 5 days a week over 7 weeks for a total of 35 fractions. Treatment continues in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cisplatin; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Onalespib; Other: Pharmacological Study

What is being measured

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

  1. Maximum tolerated dose determined by dose-limiting toxicity (DLT) of onalespib in combination with concurrent cisplatin and radiation therapy graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0

    Measured: 8 weeks

  2. Pharmacokinetic (PK) profile of onalespib in combination with cisplatin and radiation therapy

    Attempts to model associations between pharmacokinetic data with toxicity profiles will be performed primarily using descriptive statistics; however, logistic regression may be used if warranted.

    Measured: Baseline, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours on day -7; baseline, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours on day 9; and baseline on day 24

  3. PK profile of cisplatin in combination with concurrent onalespib and radiotherapy

    Attempts to model associations between pharmacokinetic data with toxicity profiles will be performed primarily using descriptive statistics; however, logistic regression may be used if warranted.

    Measured: Baseline, at end of cisplatin infusion, at 2, 4, 6, and 8-9 on day 8, and 24 hours on day 9, and at baseline on days 22 and 29

Secondary outcomes (3)

  1. Incidence of non-DLT adverse events (AEs)

    Frequency and severity of AEs will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. AEs will be summarized using all AEs experienced, although a sub-analysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to one or both study treatments. Attempts to model associations between pharmacokinetic data with toxicity profiles will be performed primarily using descriptive statistics; however, logistic regression may be used if warranted.

    Measured: Up to 2 years

  2. Antitumor activity

    Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Potential predictors include clinical predictors and molecular correlates. Descriptive statistics and plotting of data will also be used to better understand potential relationships.

    Measured: Up to 2 years

  3. Predictive biomarkers for individual cancer patients utilizing biopsies and genomic sequencing technologies

    Measured: Up to week 7

Timeline

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

  1. First posted6 Mar 2015 (estimated)
  2. Study start22 Oct 2015
  3. Primary completion24 Apr 2020
  4. Study completion24 Apr 2020

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
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02381535
Sponsor's protocol ID
NCI-2015-00256
Other IDs
NCI-2015-00256, PJC-017, 9874, 9874, UM1CA186644, UM1CA186709
Status last verified
Feb 2025
First submitted
5 Mar 2015
Last updated
11 Feb 2025
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cisplatin, Intensity-Modulated Radiation Therapy and Laboratory Biomarker Analysis in people with Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7 and Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7, run by National Cancer Institute (NCI) at 2 sites in 2 countries.

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 17 inclusion and 20 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 11 Feb 2025. 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, Canada. 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 determined by dose-limiting toxicity (DLT) of onalespib in combination with concurrent cisplatin and radiation therapy graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (time frame: 8 weeks). The study lists 3 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 NCT02381535.

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 11 Feb 2025.

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