A Phase II Trial of AZD1775 Plus Carboplatin-Paclitaxel in Squamous Cell Lung Cancer
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.
Determine the progression-free survival of carboplatin-paclitaxel plus AZD1775 in patients with advanced/metastatic SQCLC.
1. Estimate time-to-event variables, such as overall survival time, duration of overall response, and duration of stable disease.
2. Estimate the disease control rates (complete response, partial response, and stable disease).
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 from completion on chemotherapy 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
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.
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 > 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).
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