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

NCT ID: NCT01447732

Last Updated: 2024-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2015-01-31

Brief Summary

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.

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).

Conditions

Solid Tumour; Adenocarcinoma of the Colorectal; Adenocarcinoma of the Pancreas

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1

Dose escalation in subjects with advanced solid tumors with Part 1 which includes intervention of CEP-37250/KHK2804

Group Type: EXPERIMENTAL

CEP-37250/KHK2804

Intervention Type: DRUG

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 1 includes intervention of CEP-37250/KHK2804.

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

Part 2

Subjects with colorectal or pancreatic cancer Part 2 which includes intervention of CEP-37250/KHK2804

Group Type: EXPERIMENTAL

CEP-37250/KHK2804

Intervention Type: DRUG

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 1 includes intervention of CEP-37250/KHK2804.

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

Interventions

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 1 includes intervention of CEP-37250/KHK2804.

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

Intervention Type: DRUG

Other Intervention Names

KHK2804

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Teva Pharma

INDUSTRY

Sponsor Role: collaborator

Kyowa Hakko Kirin Pharma, Inc.

INDUSTRY

Sponsor Role: collaborator

Kyowa Kirin Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Tirgan, MD

Role: STUDY_DIRECTOR

Kyowa Hakko Kirin Pharma, Inc.

References

Mita MM, Nemunaitis J, Grilley-Olson J, El-Rayes B, Bekaii-Saab T, Harvey RD, Marshall J, Zhang X, Strout V. Phase 1 Study of CEP-37250/KHK2804, a Tumor-specific Anti-glycoconjugate Monoclonal Antibody, in Patients with Advanced Solid Tumors. Target Oncol. 2016 Dec;11(6):807-814. doi: 10.1007/s11523-016-0449-2.

Reference Type: DERIVED

PMID: 27457707 (View on PubMed)

Other Identifiers

CEP-37250/KHK2804-001

Identifier Type: -

Identifier Source: org_study_id