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

NCT01268059 | Terminated Phase 1 Results DMC

• 1 other identifier: CD-ON-MEDI-575-1031
• Study Type: interventional
• Target: 99
• Locations: 7 countries
• Sites: 29

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).

Conditions

Non-small Cell Lung Cancer

Keywords

Non-small cell lung cancer; NSCLC; MEDI-575; Platelet-derived growth factor receptor alpha

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities (DLT): Phase 1b

  A DLT was defined as: 1. Any treatment-related Grade 3 or higher non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions: 1. Grade 3 fever (in the absence of neutropenia) defined as more than (\>) 40.0 degree Celcius (\> 104.0 degree Fahrenheit) that resolved to normal or baseline within 24 hours of treatment and was not considered a serious adverse event (SAE); or 2. Grade 3 rigors/chills that responded to optimal therapy. 2. Any treatment-related Grade 3 or higher hematologic toxicity.

  From Day 1 to Day 21 of first cycle

• Progression Free-Survival (PFS)

  Progression-free survival defined as the time from randomization (randomization referred to the date of treatment assignment) to disease progression (defined according to Response Evaluation Criteria for Solid Tumors \[RECIST\] version 1.1 guidelines) or death due to any cause, whichever occurs first. Participants without progression or death at the time of analysis were censored at their last date of tumor evaluation. PFS was assessed only in North America/European Union (EU) participants. Progression-free survival was evaluated using Kaplan-Meier method.

  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 (18)

• Best Overall Response

  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)

• Objective Response Rate (ORR)

  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)

• Time to Response (TTR)

  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)

• Duration of Response (DR)

  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)

• Time to Progression (TTP)

  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)

Study Arms (2)

Carboplatin/Paclitaxel

ACTIVE COMPARATOR

Carboplatin/paclitaxel regimen (carboplatin area under the plasma concentration-time curve \[AUC\] of 6 milligram per milliliter into minute \[mg/mL\*min\], and paclitaxel 200 milligram per square meter \[mg/m\^2\]) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. Subjects were enrolled from North America/European Union (EU) and Japan regions.

Drug: Carboplatin; Drug: Paclitaxel

Carboplatin/Paclitaxel + MEDI-575

EXPERIMENTAL

Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL\*min, and paclitaxel 200 mg/m\^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. MEDI-575 alone continued in those participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575. Subjects were enrolled from North America/European Union (EU) and Japan regions.

Drug: Carboplatin; Drug: Paclitaxel; Drug: MEDI-575

Interventions

Carboplatin DRUG

Carboplatin (carboplatin area under the plasma concentration-time curve \[AUC\] of 6 milligram per milliliter into minute \[mg/mL\*min\] administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) until unacceptable toxicity, disease progression, or other reasons for participant withdrawal.

Carboplatin/Paclitaxel; Carboplatin/Paclitaxel + MEDI-575

Paclitaxel DRUG

Paclitaxel 200 milligram per square meter (mg/m\^2) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) until unacceptable toxicity, disease progression, or other reasons for participant withdrawal.

Carboplatin/Paclitaxel; Carboplatin/Paclitaxel + MEDI-575

MEDI-575 DRUG

MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. MEDI-575 alone continued in those participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575.

Carboplatin/Paclitaxel + MEDI-575

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (29)

Research Site

Fountain Valley, California, 92708, United States

Location

Research Site

Oxnard, California, 93030, United States

Location

Research Site

Chicago, Illinois, 60637, United States

Location

Research Site

Lafayette, Indiana, 47905, United States

Location

Research Site

Baton Rouge, Louisiana, 70809, United States

Location

Research Site

Annapolis, Maryland, 21401, United States

Location

Research Site

Baltimore, Maryland, 21204, United States

Location

Research Site

Baltimore, Maryland, 21231, United States

Location

Research Site

Boston, Massachusetts, 02114, United States

Location

Research Site

Danvers, Massachusetts, 01923, United States

Location

Research Site

Detroit, Michigan, 48201, United States

Location

Research Site

Omaha, Nebraska, 68144, United States

Location

Research Site

Lake Success, New York, 11042, United States

Location

Research Site

Canton, Ohio, 44718, United States

Location

Research Site

Hershey, Pennsylvania, 17033-0850, United States

Location

Research Site

Hilton Head Island, South Carolina, 29926, United States

Location

Research Site

Chattanooga, Tennessee, 37404, United States

Location

Research Site

Corpus Christi, Texas, 78404, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Ottawa, Ontario, K1H 8L6, Canada

Location

Research Site

Marseille, 13915, France

Location

Research Site

Berlin, 12351, Germany

Location

Research Site

Szombathely, 9700, Hungary

Location

Research Site

Fukuoka, 811-1347, Japan

Location

Research Site

Sunto-gun, 411-8777, Japan

Location

Research Site

Gdansk, 80-952, Poland

Location

Research Site

Lodz, 90-242, Poland

Location

Research Site

Mrozy, 05-320, Poland

Location

Research Site

Szczecin, 70-891, Poland

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Carboplatin; Paclitaxel; Tovetumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Limitations and Caveats

In conjunction with the overall risk-benefit assessment, study was terminated prematurely due to safety concerns. Change in tumor size outcome measure was not analyzed as per changed planned analysis due to premature termination of the study.

Results Point of Contact

• Title: Mohammed Dar, MD, Vice President & Head, Clinical Development, Oncology
• Organization: MedImmune, LLC

information.center@astrazeneca.com

+1 301-398-0000

Study Officials

• MedImmune LLC

  MedImmune LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2010
• First Posted: December 29, 2010
• Study Start: December 16, 2010
• Primary Completion: September 11, 2013
• Study Completion: September 11, 2013
• Last Updated: December 23, 2020
• Results First Posted: December 23, 2020

Record last verified: 2020-11

Locations

HU (1); JP (2); PL (4); FR (1); CA (1); US (19); DE (1)