AZD1775 Plus Carboplatin-Paclitaxel in Squamous Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT02513563
• Recruitment Status: Active, not recruiting
• First Posted: July 31, 2015
• Last Update Posted: February 23, 2023
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Tracking Information

• First Submitted Date: July 30, 2015
• First Posted Date: July 31, 2015
• Last Update Posted Date: February 23, 2023
• Actual Study Start Date: October 30, 2015
• Estimated Primary Completion Date: November 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 30, 2015)

Progression Free Survival (PFS) [ Time Frame: 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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 30, 2015)

• Overall Survival (OS) [ Time Frame: 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) [ Time Frame: 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.
• Duration of Stable Disease (SD) [ Time Frame: Up to 2 years ]
  Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
• Disease Control Rates (DCR) [ Time Frame: Up to 2 years ]
  DCR: Complete Response (CR), Partial Response (PR), and Stable Disease (SD).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lung Cancer

Intervention

• Drug: 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.
  Other Name: Paraplatin®
• Drug: 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.
  Other Name: TAXOL®
• Drug: 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.
  Other Name: MK1775

Study Arms

Experimental: 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.

Interventions:

• Drug: Carboplatin
• Drug: Paclitaxel
• Drug: AZD1775

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 2, 2022): 42
• Original Estimated Enrollment (submitted: July 30, 2015): 60
• Estimated Study Completion Date: November 2023
• Estimated Primary Completion Date: November 2023 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02513563
• Other Study ID Numbers: MCC-18304
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jhanelle Gray, M.D.; H. Lee Moffitt Cancer Center and Research Institute

• PRS Account: H. Lee Moffitt Cancer Center and Research Institute
• Verification Date: February 2023