Clinical trial NCT01268059: A Study of Carboplatin and Paclitaxel With or Without MEDI-575 in Untreated, Advanced Non-Small Cell Lung Cancer
Official title: A Phase 1b/2 Randomized Study of MEDI-575 in Combination With Carboplatin Plus Paclitaxel Versus Carboplatin Plus Paclitaxel Alone in Adult Subjects With Previously Untreated, Advanced Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Non-small cell lung cancer
NSCLC
MEDI-575
Platelet-derived growth factor receptor alpha
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2010-12-29
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the dose, antitumor activity, safety and pharmacology of MEDI-575 in combination with carboplatin/paclitaxel in subjects with previously untreated, advanced non-small cell lung cancer (NSCLC).

Detailed description: This is a Phase 1b/2, multicenter, open-label study of MEDI-575 to evaluate the dose, anti-tumor activity, safety, and pharmacology (pharmacokinetics, immunogenicity, and biomarkers) of MEDI-575 in combination with carboplatin/paclitaxel in subjects with previously untreated, advanced non-small cell lung cancer. This study has two phases: dose determination (Phase 1b) and randomization (Phase 2).

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed inoperable Stage IIIB or Stage IV non-small cell lung cancer according to the Seventh Edition of the American Joint Committee on Cancer (AJCC) Tumor Node Metastases (TNM) staging system (only participants with squamous cell carcinoma will be enrolled)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy of greater than or equal to (\>=) 3 months
* Prothrombin time elevation less than or equal to (\<=) Grade 2 by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) criteria (Version 4.0) is acceptable for participants on anticoagulant therapy
* Adequate hematologic function
* Adequate organ function
* Suitable candidates for therapy with carboplatin/paclitaxel
* Participants must have at least 1 lesion that is measurable using Response Evaluation Criteria for Solid Tumors
* Participants must be willing to consent to allow collection of archived NSCLC tumor samples
* Negative serum beta-human chorionic gonadotropin (beta-hCG) test (women of childbearing potential only)
* Females of childbearing potential, unless surgically sterile has a sterile male partner, is premenarchal or at least 2 years postmenopausal, or practices abstinence, must use 2 effective methods of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, or use of a condom with spermicide by the sexual partner) from screening, and must agree to continue using such precautions for 90 days after the final dose of treatment; cessation of birth control after this point should be discussed with a responsible physician
* Males, unless surgically sterile, must use 2 effective methods of birth control with a female partner and must agree to continue using such contraceptive precautions from screening through 90 days after the final dose of treatment

Exclusion Criteria:

* At discretion of the investigator regarding safety of the participants
* Concurrent enrollment in another clinical study
* Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer
* Previous monoclonal antibody (mAb) treatment specifically directed against platelet-derived growth factor (PDGF) or PDGF receptors
* History of serious allergy or reaction to any component of the MEDI-575 formulation
* Receipt of any previous systemic anticancer therapies for advanced or metastatic disease
* Previous adjuvant/neoadjuvant radiotherapy or chemotherapy for treatment of previous nonmetastatic disease is allowed provided that 6 months have elapsed from the end of such therapies to the time of enrollment
* New York Heart Association \>= Class II congestive heart failure
* History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to enrollment
* History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured
* Evidence of active infection requiring the use of systemic antimicrobial treatment within 72 hours prior to initial treatment with MEDI-575
* Use of immunosuppressive medication (inhaled and topical corticosteroids are permitted) within 7 days prior to enrollment
* Systemic immunosuppressive steroid therapy
* Participants may take replacement doses of steroids if on a stable dose for at least 2 weeks prior to enrollment
* History of active human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
* Pregnancy or lactation
* Previous medical history or evidence of an inter-current illness
* Any physical, social, or psychiatric condition which would prevent effective cooperation or participation in the study

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLT): Phase 1b
timeFrame: From Day 1 to Day 21 of first cycle
measure: Progression Free-Survival (PFS)
timeFrame: From randomization until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Secondary outcomes:
measure: Best Overall Response
timeFrame: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
measure: Objective Response Rate (ORR)
timeFrame: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
measure: Time to Response (TTR)
timeFrame: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
measure: Duration of Response (DR)
timeFrame: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
measure: Time to Progression (TTP)
timeFrame: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
measure: Overall Survival (OS)
timeFrame: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)
measure: Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs
timeFrame: From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs
timeFrame: From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)
measure: Maximum Observed Serum Concentration (Cmax) of MEDI-575 After First Dose
timeFrame: Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15
measure: Time of Maximal Observed Concentration (Tmax) of MEDI-575 After First Dose
timeFrame: Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15
measure: Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau) of MEDI-575 After First Dose
timeFrame: Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15
measure: Maximum Serum Concentration at Steady State (Cmax,ss) of MEDI-575
timeFrame: Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)
measure: Time to Maximum Serum Concentration at Steady State (Tmax,ss) of MEDI-575
timeFrame: Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)
measure: Trough Serum Concentration at Steady State (Ctrough,ss) of MEDI-575
timeFrame: Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)
measure: Percentage of Participants With Positive Anti-MEDI-575 Antibodies
timeFrame: Day 1 (prior to infusion) of Cycles 1 to 7 (21-day cycle), end of treatment, 30 and 60 days after the last dose (approximately 3 years)
measure: Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples
timeFrame: Baseline (Screening [Days -28 to -1])
measure: Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples
timeFrame: Baseline (Screening [Days -28 to -1])
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: Research Site
state: California
city: Oxnard
country: United States
facility: Research Site
state: California
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Lafayette
country: United States
facility: Research Site
state: Indiana
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: Annapolis
country: United States
facility: Research Site
state: Maryland
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Danvers
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Lake Success
country: United States
facility: Research Site
state: New York
city: Canton
country: United States
facility: Research Site
state: Ohio
city: Hershey
country: United States
facility: Research Site
state: Pennsylvania
city: Hilton Head Island
country: United States
facility: Research Site
state: South Carolina
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Corpus Christi
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Marseille cedex
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Szombathely
country: Hungary
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Mrozy
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References: