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Recurrent Hypopharyngeal Squamous Cell CarcinomaPhase 2NCT02196168

Cisplatin With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

A Phase 2 study testing Cisplatin, Laboratory Biomarker Analysis and Pharmacological Study in people with Recurrent Hypopharyngeal Squamous Cell Carcinoma and Recurrent Laryngeal Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 3 sites in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
Cisplatin, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
6 participants
Where
3 sitesCanada
Study dates
Mar 2014to Apr 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%)
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  • 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 × 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
  • Cardiac function: 12-lead electrocardiogram (ECG) with normal tracing, or non-clinically significant changes that do not require medical intervention; corrected QT (QTc) interval is to be < 470 msec
  • Women of childbearing potential and men must be surgically sterilized, practicing abstinence, or agree to use 2 birth control methods prior to study entry and for the duration of study participation including up to 30 days after the last dose of MK-1775; the 2 methods of birth control can be either 2 barrier methods or a barrier method plus a hormonal method to prevent pregnancy; the following are considered adequate barrier methods of contraception: diaphragm or sponge, and condom; other methods of contraception such as copper intrauterine device or spermicide may be used; appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents); should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • 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
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  • 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

Trial locations and contacts

3 sites in 1 country.

Canada3 sites

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Randomized Phase II Trial of Cisplatin With or Without Wee1 Kinase Inhibitor AZD1775 (MK-1775) for First-line Treatment of Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck (RM-SCCHN)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To compare the overall response rate assess the efficacy of MK-1775 (WEE1 inhibitor MK-1775) in combination with cisplatin to cisplatin alone in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) as per overall response rate (using Response Evaluation Criteria in Solid Tumors [RECIST] criteria version [v]1.1).

SECONDARY OBJECTIVES:

  1. Assess secondary measures of efficacy (progression free survival at 6 months and 12 months, overall survival rate at 12 months).

II. Assess measures of efficacy by tumor protein (p)53 status. III. Evaluate safety and tolerability. IV. Explore predictive and pharmacodynamic biomarkers.

OUTLINE:

SAFETY RUN-IN: Patients receive WEE1 inhibitor MK-1775 orally (PO) twice daily (BID) for 5 doses beginning on day 1 and cisplatin intravenously (IV) over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are randomized to 1 of 2 treatment arms.

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

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

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 1 year.

Being tested
Cisplatin, Laboratory Biomarker Analysis, Pharmacological Study, Placebo, WEE1 Inhibitor AZD1775
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Lymphoid Interstitial Pneumonia, Tongue Neoplasms

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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • PlaceboOther

    Also called placebo therapy, PLCB, sham therapy

    Given PO

  • WEE1 Inhibitor AZD1775Drug

    Also called AZD-1775, AZD1775, MK-1775, MK1775

    Given PO

Study groups in NCT02196168
Study groupRoleWhat they receive
Arm I (WEE1 inhibitor MK-1775, cisplatin)ExperimentalPatients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.
Receives: Drug: Cisplatin; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: WEE1 Inhibitor AZD1775
Arm II (placebo, cisplatin)Active comparatorPatients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.
Receives: Drug: Cisplatin; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo

What is being measured

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

  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

    Measured: Up to 1 year

Secondary outcomes (6)

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

    Gr 3, Gr 4 and Gr 5 AEs at least possibly related to study drug

    Measured: Up to 1 year

  2. Levels of Pharmacodynamic Biomarkers

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

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

  3. Levels of Predictive Biomarkers

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

    Measured: Up to day 4 of course 1

  4. Overall Survival

    Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.

    Measured: 12 months

  5. Progression Free Survival

    Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression (20% increase in the sum of the longest diameter of target lesions or a measurable increase in a non-target lesion, or the appearance of new lesions) or death, whichever occurs first.

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

  6. Progression Free Survival

    Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.

    Measured: Time from start of treatment to time of progression or death, whichever occurs first, assessed at 12 months

Timeline

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

  1. First posted21 Jul 2014 (estimated)
  2. Study startMar 2014
  3. Primary completionApr 2016
  4. Study completionApr 2016

Why it stopped: Inadequate accrual rate

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02196168
Sponsor's protocol ID
NCI-2014-00759
Other IDs
NCI-2014-00759, PHL-088, NCI 9416, PHL-088, 9416, N01CM00032
Status last verified
Mar 2017
First submitted
18 Jul 2014
Last updated
3 May 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cisplatin, Laboratory Biomarker Analysis and Pharmacological Study in people with Recurrent Hypopharyngeal Squamous Cell Carcinoma and Recurrent Laryngeal Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 3 sites in Canada.

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 18 inclusion and 14 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: stopped early, as of the sponsor's last update on 3 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Response Rate (Complete Plus Partial Response) Using RECIST Criteria v1.1 (time frame: Up to 1 year). 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 NCT02196168.

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 3 May 2017.

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