EMD 525797 in Colorectal and Ovarian Cancer Patients With Liver Metastases

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00848510
First received: February 19, 2009
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

This study is intended to test an experimental drug called EMD 525797 (Study Drug). This drug is not yet approved for sale and has only been tested in a small number of people to date (prior to this study starting another research study was carried out involving 37 healthy volunteers receiving the Study Drug). Until more is known about this Study Drug, it can only be used in research studies.

This research study is planned to answer important questions about how the Study Drug is tolerated and how it may work in patients with ovarian and colorectal cancer which has spread to the liver (i.e. metastatic cancer). The Sponsor (Merck KGaA) of this study is developing the Study Drug.


Condition Intervention Phase
Colorectal and Ovarian Cancer Patients With Liver Metastasis
Biological: EMD 525797
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Dose-escalation Study to Investigate the Safety, Tolerability, PD and PK of EMD 525797 Using DCE-MRI as a PK Measure of Response in Colorectal and Ovarian Cancer Patients With Liver Metastases After Failure of Standard Therapy

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Number of Subjects With Dose Limiting Toxicities (DLTs) [ Time Frame: Up to beginning of Week 5 ] [ Designated as safety issue: Yes ]
  • Change from Baseline in Vascular and Volumetric Response as Measured by Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) Parameters at Beginning of Week 3 [ Time Frame: Baseline, Beginning of Week 3 ] [ Designated as safety issue: No ]
    The DCE-MRI parameters included tumor K(trans) (volume transfer coefficient of contrast agent across the capillary wall, reflecting endothelial permeability and blood flow), Ve (extracellular, extravascular volume), Vp (blood plasma volume), initial area under the time-concentration curve (IAUC60) (non specific measure of the amount of contrast agent delivered and retained in the tumor), tumor volume and enhancing fraction of the tumor.


Secondary Outcome Measures:
  • Number of Subjects With Adverse Events (AEs), Serious AEs and Drug Related Reactions [ Time Frame: Up to Week 6 ] [ Designated as safety issue: Yes ]
  • Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
    Response rate is defined as the percentage of subjects achieving complete response (CR) or partial response (PR) according to RECIST Version 1.0 criteria. CR: disappearance of all target and non-target lesions and/or normalization of serum levels of tumor markers. PR: at least a 30 percent decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD of target lesions.

  • Number of Subjects With Best Overall Response [ Time Frame: Weeks 6, 11, 17, 23 and thereafter every 12 weeks until 4 weeks after last dose administration ] [ Designated as safety issue: No ]
  • Eastern Cooperative Oncology Group (ECOG) Performance Status Score [ Time Frame: Screening, Day 1 of Weeks 1, 3, 5, 7, 11, 17, 23 and thereafter every 12 weeks until 4 weeks after last dose administration ] [ Designated as safety issue: No ]
  • Immunogenicity, as characterized by Serum Levels of Anti EMD 525797 Antibodies [ Time Frame: Day 1 of Weeks 1, 3, 5, 6, 7, 11, 17, 23 and end of study (4 weeks after last dose administration) ] [ Designated as safety issue: No ]

Enrollment: 61
Study Start Date: February 2009
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EMD 525797 Biological: EMD 525797
EMD 525797 will be administered as an intravenous infusion at a dose range of 250 to 1500 milligram as defined in the protocol every 2 weeks. Subjects demonstrating clinical benefit at the beginning of Week 7 may continue treatment at the same dose until disease progression, intolerance to treatment, or withdrawal of consent.

  Eligibility

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

Inclusion Criteria:

  1. Provision of signed written informed consent;
  2. Male or female subjects, aged at least 18 years;
  3. Subjects with liver metastases (3 to 10 cm diameter) from colorectal and ovarian cancers;
  4. failure of standard cancer therapy;
  5. ECOG performance status of 0 to 1 at study entry and an estimated life expectancy of at least 3 months;
  6. Adequate hematological function, defined by absolute neutrophil count (ANC) ≥ 1.5 x .109 / L, platelet count ≥ 100 x .109 / L, and hemoglobin concentration ≥ 9 g / dL;
  7. As subjects with documented liver metastases are treated in this trial, liver function test values are accepted as followed: up to the upper limit of Grade 2 as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0. This includes total bilirubin level ≤3 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤5 x ULN.
  8. Adequate renal function defined by serum creatinine ≤1.5 x ULN or a creatinine clearance of ≥50 mL/min calculated by Cockcroft-Gault;
  9. Effective contraception (e.g., double barrier method) for both male and female subjects if the risk of conception exists. These subjects must be willing to avoid pregnancy during the study (screening to EOS) as well as for at least 3 months after the last dosing.

Exclusion Criteria:

  1. Any systemic cancer treatment within 30 days before treatment with EMD 525797;
  2. Thrombolytics or oral or parenteral anticoagulants (except to maintain patency of pre existing, permanent indwelling IV catheters) within 10 days prior to study start and during treatment;
  3. Radiotherapy, chemotherapy, surgery, or any investigational drug in the 30 days before the start of treatment in this study, and/or diagnostic biopsies within 2 weeks before the start of treatment in this study;
  4. Previous treatment with anti integrin therapy or anti angiogenic therapy within the last 6 months;
  5. Confirmed or clinically suspected brain metastases;
  6. Known hypersensitivity reactions to the study medication;
  7. History of allergic reactions to other monoclonal antibody (mAb) therapy;
  8. Uncontrolled hypertension (systolic blood pressure >180 mmHg, diastolic >100 mmHg);
  9. Current history of chronic daily aspirin therapy (ASS at doses ≤ 150 mg is permitted), bleeding disorders, and/or history of thromboembolic events;
  10. Severe peripheral vascular disease or ulceration;
  11. Unstable angina pectoris, or myocardial infarction within 6 months before start of study treatment, clinical significant abnormal ECG at screening;
  12. In women of childbearing potential, pregnancy (absence to be confirmed by beta human chorionic gonadotropin [β HCG] test, unless a subject has previously undergone hysterectomy or bilateral ovariectomy), or lactation period;
  13. Known alcohol or drug abuse;
  14. Participation in another clinical trial within the past 30 days before start of study treatment;
  15. All other significant diseases which, in the opinion of the PI, might impair the patient's tolerance of study treatment;
  16. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
  17. Legal incapacity or limited legal capacity (not applicable only in rare cases);
  18. Known HIV infection and/or active hepatitis B or C virus infections;
  19. Ongoing uncontrolled infections;
  20. Contraindications to MRI
  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: NCT00848510

Locations
United Kingdom
Christie Hospital
Manchester, United Kingdom
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Prof Sonia Quaratino, MD, PhD, Medical Responsible Merck KGaA
Principal Investigator: Prof. Gordon Jayson Christie Hospital, Cancer Research UK Dept. Medical Oncology
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00848510     History of Changes
Other Study ID Numbers: EMR 62242-003, 2008-001820-30
Study First Received: February 19, 2009
Last Updated: July 7, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee
United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasm Metastasis
Ovarian Neoplasms
Liver Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on July 31, 2014