A Study of Carboplatin and Paclitaxel With or Without MEDI-575 in Adults With Previously Untreated, Advanced Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01268059
First received: December 17, 2010
Last updated: March 5, 2014
Last verified: March 2014
  Purpose

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).


Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: Carboplatin/Paclitaxel/MEDI-575
Drug: Carboplatin/Paclitaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Evaluate safety profile of MEDI-575 when used in combination with carboplatin/paclitaxel [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    Subjects will be evaluated while receiving carboplatin/paclitaxel plus MEDI-575 to evaluate dose.


Secondary Outcome Measures:
  • Evaluate the progression-free survival of subjects following treatment [ Time Frame: 126 days ] [ Designated as safety issue: Yes ]
    Subjects will be randomized into two arms and receive either carboplatin/paclitaxel or carboplatin/paclitaxel plus MEDI-575.


Enrollment: 123
Study Start Date: December 2010
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: MEDI-575 Dose Determination Drug: Carboplatin/Paclitaxel/MEDI-575
Subjects will receive carboplatin/paclitaxel and MEDI-575 every 21 days for up to 6 cycles. MEDI-575 may continue alone after 6 cycles unless there is evidence of disease progression or intolerance of study treatment.
Active Comparator: Arm A Drug: Carboplatin/Paclitaxel
Subjects will receive carboplatin/paclitaxel (paclitaxel 200 mg/m2 and carboplatin AUC=6 mg/mL*min) for up to 6 cycles unless there is evidence of disease progression or intolerance of study treatment.
Active Comparator: Arm B Drug: Carboplatin/Paclitaxel/MEDI-575
Subjects will receive carboplatin/paclitaxel (paclitaxel 200 mg/m2 and carboplatin AUC=6mg/mL*min) plus MEDI-575 at dose determined in the Dose Determination Phase. Carboplatin/paclitaxel and MEDI-575 to be given once every 21 days as an IV infusion for up to 6 cycles. MEDI-575 may continue alone after 6 cycles unless there is evidence of disease progression or intolerance of study treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Age 18 years or older (20 years or older for subjects in the Japanese cohort) at the time of screening
  2. Written informed consent and any locally required authorization (eg, HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
  3. 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 subjects with squamous cell carcinoma will be enrolled)
  4. ECOG PS of 0 or 1 (see, Appendix 2)
  5. Life expectancy of ≥ 3 months
  6. Prothrombin time elevation ≤ Grade 2 by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) criteria (Version 4.0) is acceptable for subjects on anticoagulant therapy
  7. Adequate hematologic function defined as:
  8. Hemoglobin ≥ 9 g/dL
  9. Absolute neutrophil count (ANC) ≥ 1500/mm3
  10. Platelet count ≥ 100,000/mm3
  11. Adequate organ function defined as follows:
  12. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)

    ≤ 5 × institutional upper limit of normal (ULN) for cases involving liver metastasis and ≤ 2 × institutional ULN for all other cases

  13. Bilirubin ≤ 1.5 × ULN except in the case of subjects with documented or suspected Gilbert's disease ≤ 5 × ULN
  14. Calculated creatinine clearance (CrCl) ≥ 50 mL/min as determined by the Cockroft-Gault equation (Cockroft and Gault, 1976)
  15. Suitable candidates for therapy with carboplatin/paclitaxel
  16. Subjects must have at least 1 lesion that is measurable using RECIST (v1.1). Other nonmeasurable lesions are allowed.
  17. Subjects must be willing to consent to allow collection of archived NSCLC tumor samples
  18. Negative serum beta-human chorionic gonadotropin (β-hCG) test (women of childbearing potential only)
  19. Females of childbearing potential, unless surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy), 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
  20. 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
  21. Normal potassium at baseline
  22. Normal magnesium at baseline

Exclusion Critieria

Any of the following would exclude the subject from participation in the study:

  1. Any condition that, in the opinion of the investigator, would interfere with evaluation of the treatment or interpretation of subject safety or study results
  2. Concurrent enrollment in another clinical study
  3. Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals
  4. Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer
  5. Previous mAb treatment specifically directed against PDGF or PDGF receptors
  6. History of serious allergy or reaction to any component of the MEDI-575 formulation
  7. Receipt of any previous systemic anticancer therapies for advanced or metastatic disease including chemotherapy regimens, hormonal therapy, TKIs, radiotherapy, investigational agents, or any biological or immunological based therapies (including, but not limited to mAb therapy such as bevacizumab)
  8. 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.
  9. New York Heart Association ≥ Class II congestive heart failure (see Appendix 3) MedImmune Protocol CD-ON-MEDI-575-1031
  10. History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to enrollment
  11. History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), nonmelanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured
  12. Evidence of active infection requiring the use of systemic antimicrobial treatment within 72 hours prior to initial treatment with MEDI-575
  13. Use of immunosuppressive medication (inhaled and topical corticosteroids are permitted) within 7 days prior to enrollment
  14. Systemic immunosuppressive steroid therapy. Subjects may take replacement doses of steroids (defined as ≤ 30 mg day hydrocortisone or the equivalent) if on a stable dose for at least 2 weeks prior to enrollment
  15. History of active human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  16. Pregnancy or lactation
  17. Previous medical history or evidence of an intercurrent illness that may, in the opinion of the investigator, compromise the safety of the subject in the study
  18. Clinically significant abnormality on ECG
  19. Any physical, social, or psychiatric condition which would prevent effective cooperation or participation in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01268059

  Show 29 Study Locations
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Naimish Pandya, MD MedImmune LLC
  More Information

Additional Information:
No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01268059     History of Changes
Other Study ID Numbers: CD-ON-MEDI-575-1031
Study First Received: December 17, 2010
Last Updated: March 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
Non-small cell lung cancer
NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014