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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02196168
Other study ID # NCI-2014-00759
Secondary ID NCI-2014-00759PH
Status Terminated
Phase Phase 2
First received July 18, 2014
Last updated August 4, 2016
Start date March 2014

Study information

Verified date August 2016
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical 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. 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.


Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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.


Other known NCT identifiers
  • NCT01935037

Recruitment information / eligibility

Status Terminated
Enrollment 6
Est. completion date
Est. primary completion date April 2016
Accepts healthy volunteers No
Gender Both
Age group 19 Years and older
Eligibility Inclusion Criteria:

- 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 × 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

Exclusion Criteria:

- 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment


Related Conditions & MeSH terms

  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms
  • Neoplasms, Unknown Primary
  • Recurrent Hypopharyngeal Squamous Cell Carcinoma
  • Recurrent Laryngeal Squamous Cell Carcinoma
  • Recurrent Laryngeal Verrucous Carcinoma
  • Recurrent Lip and Oral Cavity Squamous Cell Carcinoma
  • Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary
  • Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma
  • Recurrent Oral Cavity Verrucous Carcinoma
  • Recurrent Oropharyngeal Squamous Cell Carcinoma
  • Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary
  • Stage IV Hypopharyngeal Squamous Cell Carcinoma
  • Stage IVA Laryngeal Squamous Cell Carcinoma
  • Stage IVA Laryngeal Verrucous Carcinoma
  • Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma
  • Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma
  • Stage IVA Oral Cavity Verrucous Carcinoma
  • Stage IVA Oropharyngeal Squamous Cell Carcinoma
  • Stage IVB Laryngeal Squamous Cell Carcinoma
  • Stage IVB Laryngeal Verrucous Carcinoma
  • Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma
  • Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma
  • Stage IVB Oral Cavity Verrucous Carcinoma
  • Stage IVB Oropharyngeal Squamous Cell Carcinoma
  • Stage IVC Laryngeal Squamous Cell Carcinoma
  • Stage IVC Laryngeal Verrucous Carcinoma
  • Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma
  • Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma
  • Stage IVC Oral Cavity Verrucous Carcinoma
  • Stage IVC Oropharyngeal Squamous Cell Carcinoma
  • Tongue Carcinoma

Intervention

Drug:
Cisplatin
Given IV
Other:
Laboratory Biomarker Analysis
Correlative studies
Pharmacological Study
Correlative studies
Placebo
Given PO
Drug:
WEE1 Inhibitor AZD1775
Given PO

Locations

Country Name City State
Canada Juravinski Cancer Centre at Hamilton Health Sciences Hamilton Ontario
Canada London Regional Cancer Program London Ontario
Canada University Health Network-Princess Margaret Hospital Toronto Ontario

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Overall response rate (complete plus partial response) using RECIST criteria v1.1 All analyses will be performed with an intention to treat. The one-sided Z test will be used to compare the response rate between the treatment and control groups. Up to 1 year No
Secondary Incidence of adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Up to 1 year Yes
Secondary 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. Pre-dose, at 4-8 hours on day 3 or 20-24 hours on day 4 No
Secondary 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. Up to day 4 of course 1 No
Secondary 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. 12 months No
Secondary 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. Time from start of treatment to time of progression or death, whichever occurs first, assessed at 6 months No
Secondary 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. Time from start of treatment to time of progression or death, whichever occurs first, assessed at 12 months No
See also
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Recruiting NCT04862650 - Cemiplimab, Low-Dose Paclitaxel and Carboplatin for the Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck Phase 2
Completed NCT01256385 - Temsirolimus With or Without Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Cancer Who Did Not Respond to Previous Therapy Phase 2
Completed NCT03032250 - Prepare to Care, A Supported Self-Management Intervention for Head and Neck Cancer CaregiversHead and Neck Cancer N/A
Recruiting NCT04754321 - Combining Immunotherapy Salvage Surgery & IORT Tx Persistent/Recurrent Head & Neck Cancer Phase 1
Terminated NCT02388932 - Stereotactic Body Radiation Therapy in Treating Patients With High Risk Locally Advanced Head and Neck Cancer N/A
Recruiting NCT05063552 - Testing the Use of Investigational Drugs Atezolizumab and/or Bevacizumab With or Without Standard Chemotherapy in the Second-Line Treatment of Advanced-Stage Head and Neck Cancers Phase 2/Phase 3
Recruiting NCT04588038 - NT-I7 for the Treatment of Recurrent Squamous Cell Carcinoma of Head and Neck Undergoing Surgery Phase 1
Active, not recruiting NCT04576091 - Testing the Addition of an Anti-cancer Drug, BAY 1895344, With Radiation Therapy to the Usual Pembrolizumab Treatment for Recurrent Head and Neck Cancer Phase 1
Recruiting NCT05172258 - Testing the Addition of an Anti-cancer Drug, Ipatasertib, to the Usual Immunotherapy Treatment (Pembrolizumab) in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck Phase 2
Active, not recruiting NCT02007200 - Soy Isoflavones in Preventing Head and Neck Cancer Recurrence in Patients With Stage I-IV Head and Neck Cancer Undergoing Surgery Phase 2
Completed NCT01064479 - Combination Chemotherapy With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck Phase 2
Completed NCT00458978 - Cediranib Maleate in Treating Patients With Recurrent or Newly Diagnosed Metastatic Head and Neck Cancer Phase 2
Completed NCT01254617 - Lenalidomide and Cetuximab in Treating Patients With Advanced Colorectal Cancer or Head and Neck Cancer Phase 1
Active, not recruiting NCT01267240 - Capecitabine and Vorinostat in Treating Patients With Recurrent and/or Metastatic Head and Neck Cancer Phase 2
Active, not recruiting NCT00588770 - Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Phase 3
Recruiting NCT04671667 - Testing What Happens When an Immunotherapy Drug (Pembrolizumab) is Given by Itself Compared to the Usual Treatment of Chemotherapy With Radiation After Surgery for Recurrent Head and Neck Squamous Cell Carcinoma Phase 2
Active, not recruiting NCT00494182 - Sorafenib in Combination With Carboplatin and Paclitaxel in Treating Participants With Metastatic or Recurrent Head and Neck Squamous Cell Cancer Phase 2
Terminated NCT02068157 - Interstitial Photodynamic Therapy in Treating Patients With Recurrent Head and Neck Cancer Phase 2