Lung Cancer
Conditions
Keywords
Squamous cell lung cancer
Brief summary
The purpose of this study is to find out what effects (good and bad) AZD1775 used in combination with carboplatin and paclitaxel will have on participants and their cancer.
Interventions
DRUGCarboplatin
Participants will be treated with carboplatin (area under the curve 5 (AUC5) will be used to determine the dosage) twice daily, days 1 and 2 and once a day on day 3 (5 doses) during each 21 day cycle of treatment.
DRUGPaclitaxel
Participants will be treated with paclitaxel 175 mg/m\^2 twice daily, days 1 and 2 and once a day on day 3 (5 doses) during each 21 day cycle of treatment.
DRUGAZD1775
Participants will receive AZD1775 225 mg twice daily, days 1 and 2 and once a day on day 3 (5 doses) during each 21 day cycle of treatment.
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent prior to any study specific procedures * Histologic or cytological diagnosis of Squamous Cell Lung Cancer (SQCLC) with advanced/metastatic stage, with no known curative treatment options. Prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation therapy given for locally advanced disease is considered first line therapy only if recurrent (local or metastatic) disease developed within 6 months of completing therapy. Potential participants with recurrent disease \> 6 months will be eligible. * Female or male aged \>/= 18 years * Eastern Cooperative Oncology Group (ECOG) performance status of 0/1 * Prior chemotherapy in the adjuvant setting is allowed * Prior radiotherapy is allowed * Any prior palliative radiation must have been completed at least 7 days prior to the start of the studies drugs and participants must have been recovered from any acute adverse effects prior to the start of the study treatment * Prior Immunotherapy with PD1i, PDL1i, anti-CTLA -4 or vaccines is allowed * Must have normal organ and marrow function * Have archival tissue available or undergo a fresh biopsy where clinically feasible after discussion with the sponsor * Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation and women who are breast feeding are excluded from the study. Both women and men should be fully informed of the lack of reproductive toxicity testing, and women must have a negative pregnancy test prior to enrollment.
Exclusion criteria
* Progressive, symptomatic untreated brain metastases * Pregnancy or breast feeding * A serious uncontrolled medical disorder or active infection that in the investigator's opinion would impair the participant's ability to receive study treatment * Prior use of platinum or paclitaxel for stage IV Non-small Cell Lung Cancer (NSCLC) or concurrent use of other anticancer approved or investigational agents * Use of anti-cancer treatment drug ?21 days or 5 half-lives (whichever is shorter) prior to the first dose of AZD1775. For drugs for which 5 half-lives is \<21 days, a minimum of 10 days between termination of the prior treatment and administration of AZD1775 treatment is required. * Major surgical procedures ?28 days of beginning study treatment, or minor surgical procedures ?7 days. No waiting period required following port-a-cath or other central venous access placement. * Grade \>1 toxicity from prior therapy EXCEPT: Alopecia, anorexia, and/or endocrinopathies on replacement therapy. * Unable to swallow oral medications. Note: Patient may not have a percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN). * Known Hepatitis B or C or HIV infection * Second primary malignancy, other than in situ malignancies or adequately treated basal cell carcinoma of the skin or other malignancy treated at least 2 years previously with no evidence of recurrence * Any of the following cardiac diseases currently or within the last 6 months: unstable angina pectoris, acute myocardial infarction, congestive heart failure \> Class 2 (as defined by New York Heart Association (NYHA)), conduction abnormality not controlled with pacemaker or medication, significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible) * Have had prescription or non-prescription drugs or other products (i.e., grapefruit juice) known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4, which cannot be discontinued 2 weeks before Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug * Co-administration of aprepitant and fosaprepitant during this study is prohibited * AZD1775 is an inhibitor of breast cancer resistance protein (BCRP). The use of statins including Atorvastatin which are substrates for BCRP are therefore prohibited and patients should be moved on to non-BCRP alternatives * Herbal preparations are not allowed throughout the study. These herbal medications include, but are not limited to: St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng * History of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected * Mean resting corrected QTc interval using the Fridericia formula (QTcF) \>450 msec/male and \>470 msec/female (as calculated per institutional standards) obtained from 1 electrocardiograms (ECGs).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Up to 2 years | PFS is measured from date of first study treatment to death, progression of disease, or the last follow-up data, whichever comes first. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 2 years | OS is defined as the duration of time from the date for first treatment (Cycle 1 Day 1) to the date of death. |
| Duration of Overall Response (OR) | Up to 2 years | The duration of overall response is measured from the time measurement criteria are met for Complete Response (CR) or Partial Response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. |
| Percentage of Participants With Disease Control | Up to 2 years | DCR: Complete Response (CR), Partial Response (PR), and Stable Disease (SD). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJhanelle Gray, M.D.
H. Lee Moffitt Cancer Center and Research Institute
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Carboplatin/Paclitaxel/AZD1775 Treatment: Combination of AZD1775 plus carboplatin and paclitaxel. Participants will be treated with this combination of drugs twice daily on days 1 and 2 and once on day 3 for a total of 5 doses during each 21 day cycle of treatment.
Carboplatin: Participants will be treated with carboplatin (area under the curve 5 (AUC5) will be used to determine the dosage) twice daily, days 1 and 2 and once a day on day 3 (5 doses) during each 21 day cycle of treatment.
Paclitaxel: Participants will be treated with paclitaxel 175 mg/m\^2 twice daily, days 1 and 2 and once a day on day 3 (5 doses) during each 21 day cycle of treatment.
AZD1775: Participants will receive AZD1775 225 mg twice daily, days 1 and 2 and once a day on day 3 (5 doses) during each 21 day cycle of treatment. | 42 |
| Total | 42 |
Baseline characteristics
| Characteristic | Carboplatin/Paclitaxel/AZD1775 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 23 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Region of Enrollment United States | 42 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 42 |
| other Total, other adverse events | 40 / 42 |
| serious Total, serious adverse events | 26 / 42 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS is measured from date of first study treatment to death, progression of disease, or the last follow-up data, whichever comes first. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: Up to 2 years
Population: Evaluable participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel/AZD1775 | Progression Free Survival (PFS) | 4.8 months |
Secondary
Duration of Overall Response (OR)
The duration of overall response is measured from the time measurement criteria are met for Complete Response (CR) or Partial Response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Up to 2 years
Population: Evaluable participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel/AZD1775 | Duration of Overall Response (OR) | 4.4 months |
Secondary
Overall Survival (OS)
OS is defined as the duration of time from the date for first treatment (Cycle 1 Day 1) to the date of death.
Time frame: Up to 2 years
Population: Evaluable participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel/AZD1775 | Overall Survival (OS) | 7.3 months |
Secondary
Percentage of Participants With Disease Control
DCR: Complete Response (CR), Partial Response (PR), and Stable Disease (SD).
Time frame: Up to 2 years
Population: Evaluable participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Carboplatin/Paclitaxel/AZD1775 | Percentage of Participants With Disease Control | 61 percentage |