NCT02196168

Brief Summary

This randomized phase II trial studies how well cisplatin with or without WEE1 inhibitor MK-1775 works in treating patients with head and neck cancer that has come back or has spread to other parts of the body. Drugs used in chemotherapy, such as cisplatin, may prevent tumor cells from multiplying by damaging their deoxyribonucleic acid (DNA), which in turn stops the tumor from growing. WEE1 inhibitor MK-1775 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cisplatin is more effective with or without WEE1 inhibitor MK-1775 in treating patients with head and neck cancer.

Trial Health

57
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Mar 2014

Geographic Reach
1 country

3 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2014

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

July 18, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 21, 2014

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2016

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

May 3, 2017

Completed
Last Updated

May 3, 2017

Status Verified

March 1, 2017

Enrollment Period

2.1 years

First QC Date

July 18, 2014

Results QC Date

November 18, 2016

Last Update Submit

March 22, 2017

Conditions

Outcome Measures

Primary Outcomes (1)

  • Overall Response Rate (Complete Plus Partial Response) Using RECIST Criteria v1.1

    Per Response Evaluation Criteria in solid Tumors (RECIST1.1) Target lesions are assessed as Complete Response(CR), Disappearance of all target lesions; Partial Response (PR),30% decrease in the sum of the diameters of target lesions; Progressive Disease (PD), At least a 20% increase (minimum 5 mm) from smallest sum (nadir); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Nontarget lesions are assessed as Complete Response (CR), Disappearance of all non-target lesions; Non-CR/Non-PD, Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits; Progressive Disease (PD),Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions; Overall Response(OR); PR=CR+non-CR/non-PD,SD=SD+non-PD; PD=PD+presence of any non-target lesions

    Up to 1 year

Secondary Outcomes (6)

  • Incidence of Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

    Up to 1 year

  • Levels of Pharmacodynamic Biomarkers

    Pre-dose, at 4-8 hours on day 3 or 20-24 hours on day 4

  • Levels of Predictive Biomarkers

    Up to day 4 of course 1

  • Overall Survival

    12 months

  • Progression Free Survival

    Time from start of treatment to time of progression or death, whichever occurs first, assessed at 6 months

  • +1 more secondary outcomes

Study Arms (2)

Arm I (WEE1 inhibitor MK-1775, cisplatin)

EXPERIMENTAL

Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.

Drug: CisplatinOther: Laboratory Biomarker AnalysisOther: Pharmacological StudyDrug: WEE1 Inhibitor AZD1775

Arm II (placebo, cisplatin)

ACTIVE COMPARATOR

Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.

Drug: CisplatinOther: Laboratory Biomarker AnalysisOther: Pharmacological StudyOther: Placebo

Interventions

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
Arm I (WEE1 inhibitor MK-1775, cisplatin)Arm II (placebo, cisplatin)

Correlative studies

Arm I (WEE1 inhibitor MK-1775, cisplatin)Arm II (placebo, cisplatin)

Correlative studies

Arm I (WEE1 inhibitor MK-1775, cisplatin)Arm II (placebo, cisplatin)
PlaceboOTHER

Given PO

Also known as: placebo therapy, PLCB, sham therapy
Arm II (placebo, cisplatin)

Given PO

Also known as: AZD-1775, AZD1775, MK-1775, MK1775
Arm I (WEE1 inhibitor MK-1775, cisplatin)

Eligibility Criteria

Age19 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must have histologically or cytologically confirmed SCCHN that is recurrent and/or metastatic and not amendable to curative therapy by surgery or radiation; SCCHN originating from the following sites are eligible: oral cavity, oropharynx, larynx, hypopharynx and paranasal sinus; for patients with a diagnosis of SCCHN of unknown origin, their eligibility must be reviewed and approved by the principal investigator
  • No prior systemic chemotherapy or WEE1 kinase inhibitor therapy for metastatic or recurrent disease will be allowed; patients are permitted to have received prior systemic chemotherapy as a part of the initial multimodality treatment for locally advanced disease if this treatment was completed more than 6 months prior to enrollment
  • Patients must have disease amenable to biopsy and must be medically fit to undergo a biopsy
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> 10 mm with computed tomography (CT) scan; indicator lesions must not have been previously treated with surgery, radiation therapy or radiofrequency ablation unless there is documented progression after therapy
  • Patients must have completed any previous surgery or radiotherapy \>= 4 weeks prior to enrollment
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky \> 60%)
  • Life expectancy of greater than 12 weeks
  • Leukocytes \>= 3,000/mcL
  • Absolute neutrophil count \>= 1,500/mcL
  • Platelets \>= 100,000/mcL
  • Hemoglobin \>= 9 g/dL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 Ă— institutional upper limit of normal
  • Prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized ratio (INR) =\< 1.5 upper limit of normal (ULN)
  • Creatinine within normal institutional limits OR calculated creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with levels above institutional normal using modified Cockcroft-Gault
  • +3 more criteria

You may not qualify if:

  • Past or current malignancy other than SCCHN, except for:
  • Cervical carcinoma stage 1B or less
  • Non-invasive basal cell and squamous cell skin carcinoma
  • Malignant melanoma with a complete response of a duration of \> 10 years
  • Radically treated prostate cancer (prostatectomy or radiotherapy) with normal prostate specific antigen (PSA), and not requiring ongoing anti-androgen hormonal therapy
  • Other cancer diagnosis with a complete response of duration of \> 5 years
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-1775 or cisplatin
  • Patients who are unable to take oral medications and/or who have a clinical or radiological diagnosis of bowel obstruction are ineligible
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, active peptic ulcer disease, myocardial infarction within 6 months prior to entry, congestive heart failure, symptomatic congestive heart failure, active cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MK-1775
  • Human immunodeficiency virus (HIV)-positive patients are ineligible
  • Patients taking the following prescription or non-prescription drugs or other products (i.e. grapefruit juice) are ineligible: sensitive cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates, CYP3A4 substrates with a narrow therapeutic index, moderate to potent inhibitors/inducers of CYP3A4; patients would be eligible if the medications can be discontinued two weeks prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and NeckLymphoid Interstitial PneumoniaTongue Neoplasms

Interventions

Cisplatin1,2-diaminocyclohexaneplatinum II citratePlatinumadavosertib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsHead and Neck NeoplasmsNeoplasms by SiteMouth NeoplasmsMouth DiseasesStomatognathic DiseasesTongue Diseases

Intervention Hierarchy (Ancestors)

Chlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsMetals, HeavyElementsTransition ElementsMetals

Results Point of Contact

Title
Dr.Eric Winquist
Organization
London Health Sciences centre

Study Officials

  • Eric Winquist

    University Health Network Princess Margaret Cancer Center P2C

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 18, 2014

First Posted

July 21, 2014

Study Start

March 1, 2014

Primary Completion

April 1, 2016

Study Completion

April 1, 2016

Last Updated

May 3, 2017

Results First Posted

May 3, 2017

Record last verified: 2017-03

Locations