Clinical trial NCT02513563: AZD1775 Plus Carboplatin-Paclitaxel in Squamous Cell Lung Cancer
Official title: A Phase II Trial of AZD1775 Plus Carboplatin-Paclitaxel in Squamous Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: Squamous cell lung cancer
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
First posted: 2015-07-31
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Duration of Overall Response (OR)
timeFrame: Up to 2 years
measure: Percentage of Participants With Disease Control
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Jhanelle Gray, M.D.
role: PRINCIPAL_INVESTIGATOR
References: