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

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:

MedlinePlus related topics: Cancer

U.S. FDA Resources

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:	January 2014
Estimated Primary Completion Date:	December 2013 (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

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

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: Nehal Mohamed, PhD	609.919.1100	nmohamed@kyowa-kirin.pharma.com

Locations

United States, California
Cedars Sinai Medical Center	Not yet recruiting
Los Angeles, California, United States, 90048
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	Not yet 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:

Bruce Silvers, 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:	August 21, 2012
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:

Adenocarcinoma
Adenocarcinoma, Mucinous
Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

Neoplasms, Cystic, Mucinous, and Serous
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013