Phase 1 Study of CEP-37250/KHK2804 in Subjects With Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Kyowa Hakko Kirin Pharma, Inc.
Sponsor:
Collaborator:
Teva Pharma
Information provided by (Responsible Party):
Kyowa Hakko Kirin Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT01447732
First received: September 30, 2011
Last updated: January 22, 2014
Last verified: January 2014
  Purpose

This is a two-part, Phase 1 open label, multi-center, dose escalation study of CEP-37250/KHK2804 as monotherapy in subjects with advanced solid tumors who no longer respond to standard therapy or for whom no standard therapy is available.


Condition Intervention Phase
Solid Tumour
Adenocarcinoma of the Colorectal
Adenocarcinoma of the Pancreas
Drug: CEP-37250/KHK2804
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Two-Part, Open-Label, Multi-Center Phase 1 Study of Monoclonal Antibody CEP-37250/KHK2804 in Subjects With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Kyowa Hakko Kirin Pharma, Inc.:

Primary Outcome Measures:
  • Adverse Event collection and assessment will be done for all 74 potentially treated subjects. [ Time Frame: at least 30 days or up to 12 weeks ] [ Designated as safety issue: Yes ]
    The safety of CEP-37250/KHK2804 will be determined by reported adverse events (AEs), changes in the physical examinations, vital laboratory evaluations, and treatment discontinuations due to toxicity.


Secondary Outcome Measures:
  • To assess PK parameters which include: area under the plasma concentration versus time curve (AUC), peak plasma concentration (Cmax), t 1/2 and CL of CEP-37250/KHK2804. [ Time Frame: at least 30 days or up to 12 weeks ] [ Designated as safety issue: No ]
    Participating subjects will have serial blood samples taken to determine the PK profile of study drug.

  • To screen for the development of antibodies against CEP-37250/KHK2804 (immunogenicity) [ Time Frame: at least 30 days or up to 12 weeks ] [ Designated as safety issue: Yes ]
    Subjects will have serial blood samples to check for the developments of anti-CEP-37250/KHK2804 antibodies.

  • To evaluate preliminary efficacy (overall response (Objective response rate(ORR; Complete Response(CR)+Partial Response(PR) and clinical benefit rate(CR+PR+stable disease(SD)). [ Time Frame: up to 30 days or up to 12 weeks ] [ Designated as safety issue: Yes ]
    Tumor measurements and disease response assessments will be performed on all participating subjects.


Estimated Enrollment: 74
Study Start Date: October 2011
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1
Dose escalation in subjects with advanced solid tumors
Drug: CEP-37250/KHK2804

Part 1 is based on the CEP-37250/KHK2804 tolerability and safety data from three subjects enrolled in a cohort, enrollment at the next dose level or additional subjects into the ongoing cohort will occur based upon the number subjects with DLT at a given dose level. Dose depends on subject's body weight.

Part 2 will receive CEP-37250/KHK2804 at a dose to be determined following completion of Part 1.

Other Name: KHK2804
Experimental: Part 2
Subjects with colorectal or pancreatic cancer
Drug: CEP-37250/KHK2804

Part 1 is based on the CEP-37250/KHK2804 tolerability and safety data from three subjects enrolled in a cohort, enrollment at the next dose level or additional subjects into the ongoing cohort will occur based upon the number subjects with DLT at a given dose level. Dose depends on subject's body weight.

Part 2 will receive CEP-37250/KHK2804 at a dose to be determined following completion of Part 1.

Other Name: KHK2804

Detailed Description:

The study will be conducted in two parts. In Part 1, a standard 3+3 designed dose escalation phase, subjects will receive CEP-37250/KHK2804, administered iv, once every week. A treatment cycle will consists of total of four doses per cycle. Part 2 of the study will enroll subjects with either colon cancer or pancreatic cancer to receive CEP-37250/KHK2804 at a dose to be determined following completion of Part 1.

All subjects will receive study therapy until disease progression, the development of unacceptable toxicity, noncompliance or withdrawal of consent by the subject, or Investigator decision, up to a maximum of six cycles (approximately six months). After six cycles of CEP-37250/KHK2804 therapy, the subject may continue to receive CEP-37250/KHK2804 after discussion with the Sponsor and determination that the subject is experiencing a best response of at least stable disease (SD) and is not experiencing any unacceptable toxicities or dose limiting toxicities (DLTs).

  Eligibility

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

Inclusion Criteria:

  • Adequate hepatic, renal, and hematologic function;
  • Life expectancy > 3 months;
  • Part 1 and 2: The subject has histopathologically or cytologically documented, measurable, unresectable, locally advanced primary or recurrent, metastatic solid tumor, locally advanced primary or recurrent, metastatic pancreatic adenocarcinoma and must have received at least one prior treatment regimen containing gemcitabine or 5-FU, and locally advanced primary or recurrent, metastatic colon adenocarcinoma.

Exclusion Criteria:

  • Parts 1 and 2:

    1. Malignant melanoma, Merkel cell cancer, small cell lung cancer, lymphoepithelial carcinoma, malignant mesothelioma, GIST, Hodgkin and NHL, thymoma, neuroendocrine, neuronal tumors, and sarcomas. This list of excluded tumors may be modified as additional research findings become available on target antigen expression;
    2. The subject has received anti-cancer chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks (6 weeks for mitomycin C and nitrosoureas) prior to the first dose of CEP-37250/KHK2804;
    3. The subject has received monoclonal antibodies of any type or for any form of disease within 4 weeks of the first dose of CEP-37250/KHK2804;
    4. Major surgery within 4 weeks prior to the first dose;
    5. Known symptomatic brain metastases (screening magnetic resonance imaging (MRI) of the brain is only required when there is clinical suspicion of central nervous system [CNS] involvement or past history of treated brain metastasis). Subjects with treated brain metastasis (radiotherapy and/or surgery) will be eligible if they:
  • Have completed treatment for their brain metastasis > 4 weeks prior to scheduled study treatment start date;
  • Are neurologically stable;
  • Are on corticosteroids in doses no greater than physiological replacement (e.g., dexamethasone < 1.5 mg/day); and
  • Have a screening MRI scan of the brain that specifically verifies no evidence of CNS hemorrhage and no active gadolinium enhancing lesions;
  • Subjects with primary brain/CNS malignancy (e.g., gliomas, lymphomas) are excluded.

    • Hypersensitivity reaction to monoclonal antibodies, other therapeutic proteins, or allergy to any component of the CEP-37250/KHK2804 finished drug and the reaction could not be controlled or prevented on subsequent infusion with standard therapies such as antihistamines, 5-HT3 antagonists, or corticosteroids.
  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: NCT01447732

Contacts
Contact: Mei M Hentrup, BSN, BS 609.580.7414 mhentrup@kyowa-kirin-pharma.com
Contact: Vincent Strout, MBA 609.919.1100 vstrout@kyowa-kirin-pharma.com

Locations
United States, California
Cedars Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
United States, District of Columbia
Georgetown University Medical Center Not yet recruiting
Washington, District of Columbia, United States, 20007
Principal Investigator: John Marshall, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
United States, North Carolina
UNC - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
United States, Texas
Mary Crowley Cancer Center Recruiting
Dallas, Texas, United States, 75201
Sponsors and Collaborators
Kyowa Hakko Kirin Pharma, Inc.
Teva Pharma
Investigators
Study Director: Michael Tirgan, MD Kyowa Hakko Kirin Pharma, Inc.
  More Information

No publications provided

Responsible Party: Kyowa Hakko Kirin Pharma, Inc.
ClinicalTrials.gov Identifier: NCT01447732     History of Changes
Other Study ID Numbers: CEP-37250/KHK2804-001
Study First Received: September 30, 2011
Last Updated: January 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Kyowa Hakko Kirin Pharma, Inc.:
Monoclonal antibody (Mab)
Antibody dependent cellular cytotoxicity (ADCC)
Complement-dependent toxicity (CDC)
Non-fucosylated immunoglobulin G

Additional relevant MeSH terms:
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014