WEE1 Inhibitor MK-1775, Docetaxel, and Cisplatin Before Surgery in Treating Patients With Borderline Resectable Stage III-IVB Squamous Cell Carcinoma of the Head and Neck

NCT02508246 | Completed Phase 1

• 3 other identifiers: 9168NCI-2015-01064P30CA015704
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and the best dose of WEE1 inhibitor MK-1775 when given together with docetaxel and cisplatin in treating patients with stage III-IVB squamous cell carcinoma of the head and neck that may or may not be able to be removed by surgery (borderline resectable). WEE1 inhibitor MK-1775 may block the growth of tumor cells by blocking some of enzymes that are needed for tumor growth and may also help docetaxel and cisplatin work better by making tumor cells more sensitive to the drug. Drugs used in chemotherapy, such as docetaxel and 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. Giving WEE1 inhibitor MK-1775 with docetaxel and cisplatin before surgery may kill more tumor cells and shrink the tumor, allowing patients to undergo surgery to remove it.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events graded according to the NCI CTCAE version 4.03

  Summary tables and graphic displays, as appropriate, will be prepared to examine the distribution of these toxicities per cycle.

  Up to 2 years post-treatment

• MTD of AZD1775, based on the incidence of dose limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

  DLT is defined as any adverse event judged by the investigator to be drug-related (i.e., causality rated as possible or greater) that is assessed as grade 3 or worse. Summary tables and graphic displays, as appropriate, will be prepared to examine the distribution of these toxicities per cycle.

  28 days

Secondary Outcomes (4)

• Objective response (complete response, partial response, stable disease or progressive disease) according to Response Evaluation Criteria In Solid Tumors

  Up to 5 years post-treatment

• Pharmacodynamic profile of AZD1775

  Time of surgery or up to day 29

• PK profile of WEE1 inhibitor MK-1775 with docetaxel and cisplatin

  Pre-dose and at 1, 2, 4, 6, and 8-10 hours on days 2 and 4 of course 1, and pre-dose on day 3 of course 1

• Progression-free survival (PFS) duration

  Up to 5 years post-treatment

Study Arms (1)

Treatment (WEE1 inhibitor MK-1, cisplatin, docetaxel, surgery)

EXPERIMENTAL

Patients receive WEE1 inhibitor MK-1775 PO BID on days 2-4, 9-11, and 16-18, and day -7 prior to course 1, day 1 for PD assessment. Patients also receive cisplatin IV on days 1 (or up to two days after last dose of WEE1 inhibitor MK-1775 lead-in is completed), 8 (or 7 days after first chemotherapy dose), and 15, and docetaxel IV on days 1, 8, and 15. Patients experiencing progressive disease undergo surgical resection. Patients not deemed surgically resectable proceed to chemoradiation as clinically indicated. Patients experiencing stable disease or partial response may receive 2 additional courses of treatment every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cisplatin; Drug: Docetaxel; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery; Drug: WEE1 Inhibitor AZD1775

Interventions

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Treatment (WEE1 inhibitor MK-1, cisplatin, docetaxel, surgery)

Docetaxel DRUG

Given IV

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Treatment (WEE1 inhibitor MK-1, cisplatin, docetaxel, surgery)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (WEE1 inhibitor MK-1, cisplatin, docetaxel, surgery)

Pharmacological Study OTHER

Correlative studies

Treatment (WEE1 inhibitor MK-1, cisplatin, docetaxel, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (WEE1 inhibitor MK-1, cisplatin, docetaxel, surgery)

WEE1 Inhibitor AZD1775 DRUG

Given PO

Also known as: AZD-1775, AZD1775, MK-1775, MK1775

Treatment (WEE1 inhibitor MK-1, cisplatin, docetaxel, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• Current diagnosis of histological or cytopathological HNSCC malignancy borderline resectable stage III up to stage IVb (T1-4, N0-2, M0) or unresectable stage IV with high nodal status defined as \>= N2b (by the American Joint Committee on Cancer \[AJCC\] 7th Edition Staging) that is amenable or appropriate for curative treatment; borderline resectability is assessed; NOTE: surgical unresectability will be defined as the combination of the treating surgeon's judgment of unresectability plus one of the following objective criteria:
• Encasement of tumor or nodes to the carotid artery or 3/4 encasement of the carotid artery
• Involvement of prevertebral musculature
• Need for glossectomy or extensive glossal resection where functional outcome is considered unacceptable to surgeon or patient
• Involvement of the cervical spine
• Severe, unacceptable functional deficit that would result from any proposed definitive surgical resection
• NOTE: the principal investigator (PI) of the study, Dr. Mendez, is a surgical ear, nose and throat (ENT) (head and neck) oncologist and all HNSCC cases will be discussed at the University of Washington/Seattle Cancer Care Alliance weekly tumor conference where two other ENT surgical oncologists, and co-investigators in this study, will help assess resectability; as surgical unresectability may vary from patient to patient based on individual anatomy, treating physicians may, with the approval of the surgical team, declare a tumor not meeting the above criteria to be unresectable; in this case, the reason for unresectability should be documented in the medical record; medical co-morbidity and poor performance status may not be used to declare a patient unresectable
• Patients must all have available tumor tissue for biopsy and not have any bleeding diathesis and/or chronic anticoagulation that cannot be stopped for the biopsy
• Eastern Cooperative Oncology Group (ECOG) 0-2
• Absolute neutrophil count (ANC) \> 1500/uL
• Hemoglobin \> 9 g/dL
• Platelets \> 100,000/uL
• Total bilirubin within 1.5 times the institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 times ULN

You may not qualify if:

• Non-squamous cell carcinomas of the head and neck region i.e. nasopharyngeal carcinoma (World Health Organization \[WHO\] type II and III) and salivary gland carcinomas
• Severe uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, uncontrollable hypertension or any other condition or circumstance that could interfere with adherence to the study's procedures or requirements, or otherwise compromise the study's objectives
• Prior treatment with any of the chemotherapy medications (cisplatin or docetaxel) for HNSCC or with AZD1775
• Prior bone marrow transplant or history of organ transplant requiring the need for any chronic immunosuppressive medications
• Prior radiation to any of the field required to treat the tumor
• Any distant metastatic disease
• Major psychiatric disorders which would limit compliance
• Neuropathy grade 2 or higher
• History of prolonged QT syndrome or electrocardiogram (ECG) at screening QT interval corrected for heart rate (QTc) of \> 470 ms with Bazett's or Fridericia's formula
• Active infection requiring systemic antibiotic therapy or causing fever (temp \> 100.5 degrees Fahrenheit \[F\] or 38.1 degrees Celsius \[C\]) within 1 week prior to dosing with AZD1775
• Pregnant or breast-feeding females
• Second primary malignancy within 3 years (not including in situ carcinoma of the cervix, non-melanoma skin cancer or low-grade \[Gleason score =\< 6\] localized prostate cancer) at the time of consideration for study enrollment
• Known prior severe allergic/hypersensitivity to the chemotherapy or any of the components of the study treatment
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow and retain the formulated oral product or previous significant bowel resection that would preclude adequate absorption of AZD1775
• Inability or unwillingness to abstain from taking any medications or herbal supplements that are moderate or strong inducers of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) at least 1 week prior dosing with AZD1775 and while on study treatment

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Docetaxel; adavosertib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Eduardo Mendez

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2015
• First Posted: July 24, 2015
• Study Start: July 22, 2015
• Primary Completion: April 26, 2018
• Study Completion: April 26, 2018
• Last Updated: March 13, 2019

Record last verified: 2019-03

Locations

US (1)