Trial Outcomes & Findings for Cisplatin With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer (NCT NCT02196168)

NCT ID: NCT02196168

Last Updated: 2017-05-03

Results Overview

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

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

Up to 1 year

Results posted on

2017-05-03

Participant Flow

Participant milestones

Participant milestones
Measure
Arm I (WEE1 Inhibitor MK-1775, Cisplatin)
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies WEE1 Inhibitor AZD1775: Given PO
Arm II (Placebo, Cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO
Overall Study
STARTED
6
0
Overall Study
COMPLETED
6
0
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Arm I (WEE1 Inhibitor MK-1775, Cisplatin)
n=6 Participants
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies WEE1 Inhibitor AZD1775: Given PO
Arm II (Placebo, Cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO
Total
n=6 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
3 Participants
n=5 Participants
3 Participants
n=5 Participants
Age, Categorical
>=65 years
3 Participants
n=5 Participants
3 Participants
n=5 Participants
Age, Continuous
66 years
n=5 Participants
66 years
n=5 Participants
Sex: Female, Male
Female
1 Participants
n=5 Participants
1 Participants
n=5 Participants
Sex: Female, Male
Male
5 Participants
n=5 Participants
5 Participants
n=5 Participants
Region of Enrollment
Canada
6 participants
n=5 Participants
6 participants
n=5 Participants

PRIMARY outcome

Timeframe: Up to 1 year

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

Outcome measures

Outcome measures
Measure
Arm I (WEE1 Inhibitor MK-1775, Cisplatin)
n=6 Participants
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies WEE1 Inhibitor AZD1775: Given PO
Arm II (Placebo, Cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO
Overall Response Rate (Complete Plus Partial Response) Using RECIST Criteria v1.1
0 Participants

SECONDARY outcome

Timeframe: Up to 1 year

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

Outcome measures

Outcome measures
Measure
Arm I (WEE1 Inhibitor MK-1775, Cisplatin)
n=6 Participants
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies WEE1 Inhibitor AZD1775: Given PO
Arm II (Placebo, Cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO
Incidence of Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
13 adverse events

SECONDARY outcome

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

Population: No data are available as decision was made by PI not to do the analysis due to small number of patients

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.

Outcome measures

Outcome measures
Measure
Arm I (WEE1 Inhibitor MK-1775, Cisplatin)
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies WEE1 Inhibitor AZD1775: Given PO
Arm II (Placebo, Cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO
Levels of Pharmacodynamic Biomarkers
0
0

SECONDARY outcome

Timeframe: Up to day 4 of course 1

Population: No data are available as decision was made by PI not to do the analysis due to small number of patients.

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.

Outcome measures

Outcome measures
Measure
Arm I (WEE1 Inhibitor MK-1775, Cisplatin)
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies WEE1 Inhibitor AZD1775: Given PO
Arm II (Placebo, Cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO
Levels of Predictive Biomarkers
0
0

SECONDARY outcome

Timeframe: 12 months

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.

Outcome measures

Outcome measures
Measure
Arm I (WEE1 Inhibitor MK-1775, Cisplatin)
n=6 Participants
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies WEE1 Inhibitor AZD1775: Given PO
Arm II (Placebo, Cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO
Overall Survival
0.21 months
Interval 0.01 to 0.6

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure
Arm I (WEE1 Inhibitor MK-1775, Cisplatin)
n=6 Participants
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies WEE1 Inhibitor AZD1775: Given PO
Arm II (Placebo, Cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO
Progression Free Survival
2.88 months
Interval 0.99 to
The upper limit for Measure of Dispersion was 'not reached' for this study

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure
Arm I (WEE1 Inhibitor MK-1775, Cisplatin)
n=6 Participants
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies WEE1 Inhibitor AZD1775: Given PO
Arm II (Placebo, Cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO
Progression Free Survival
2.88 months
Interval 0.99 to
The upper limit for Measure of Dispersion was 'not reached' for this study

Adverse Events

Arm I (WEE1 Inhibitor MK-1775, Cisplatin)

Serious events: 4 serious events
Other events: 6 other events
Deaths: 0 deaths

Arm II (Placebo, Cisplatin)

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Arm I (WEE1 Inhibitor MK-1775, Cisplatin)
n=6 participants at risk
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies WEE1 Inhibitor AZD1775: Given PO
Arm II (Placebo, Cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO
Blood and lymphatic system disorders
Febrile Neutropenia
16.7%
1/6
0/0
Investigations
lymphocyte count decreased
16.7%
1/6
0/0
Blood and lymphatic system disorders
Anemia
50.0%
3/6
0/0
Investigations
white blood cell decreased
33.3%
2/6
0/0
Investigations
neutrophil count decreased
33.3%
2/6
0/0
Musculoskeletal and connective tissue disorders
Generalized Muscle weakness
33.3%
2/6
0/0
Nervous system disorders
Dizziness
16.7%
1/6
0/0
Metabolism and nutrition disorders
Dehydration
16.7%
1/6
0/0
Respiratory, thoracic and mediastinal disorders
Lung infection
16.7%
1/6
0/0

Other adverse events

Other adverse events
Measure
Arm I (WEE1 Inhibitor MK-1775, Cisplatin)
n=6 participants at risk
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies WEE1 Inhibitor AZD1775: Given PO
Arm II (Placebo, Cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO
Blood and lymphatic system disorders
Anemia
66.7%
4/6
0/0
Investigations
Lymphocyte count decreased
33.3%
2/6
0/0
Investigations
Neutrophil count decreased
33.3%
2/6
0/0
Investigations
white blood cell decreased
33.3%
2/6
0/0
Investigations
hypophosphatemia
33.3%
2/6
0/0
Metabolism and nutrition disorders
alkalosis
16.7%
1/6
0/0
Metabolism and nutrition disorders
Dehydration
16.7%
1/6
0/0
Gastrointestinal disorders
Diarrhea
16.7%
1/6
0/0
Blood and lymphatic system disorders
Febrile Neutropenia
16.7%
1/6
0/0
Musculoskeletal and connective tissue disorders
Generalized Muscle weakness
16.7%
1/6
0/0
Metabolism and nutrition disorders
Hyponatremia
16.7%
1/6
0/0
Infections and infestations
Lung infection
16.7%
1/6
0/0
Investigations
Platelet count decreased
16.7%
1/6
0/0

Additional Information

Dr.Eric Winquist

London Health Sciences centre

Phone: 519-685-8500

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60