Onalespib in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin
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
5 other identifiers
interventional
2
2 countries
2
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Oct 2015
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 5, 2015
CompletedFirst Posted
Study publicly available on registry
March 6, 2015
CompletedStudy Start
First participant enrolled
October 22, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 24, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
April 24, 2020
CompletedFebruary 11, 2025
February 1, 2025
4.5 years
March 5, 2015
February 8, 2025
Conditions
Outcome Measures
Primary Outcomes (3)
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
8 weeks
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.
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
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.
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)
Incidence of non-DLT adverse events (AEs)
Up to 2 years
Antitumor activity
Up to 2 years
Predictive biomarkers for individual cancer patients utilizing biopsies and genomic sequencing technologies
Up to week 7
Study Arms (1)
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.
Interventions
Given IV
Undergo IMRT
Given IV
Eligibility Criteria
You may qualify if:
- 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
- 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
- +2 more criteria
You may not qualify if:
- 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
- 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)
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Yale University
New Haven, Connecticut, 06520, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew J Hope
University Health Network Princess Margaret Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 5, 2015
First Posted
March 6, 2015
Study Start
October 22, 2015
Primary Completion
April 24, 2020
Study Completion
April 24, 2020
Last Updated
February 11, 2025
Record last verified: 2025-02