Phase I Study to Determine the Maximum Tolerable Dose of BAY94-9343 in Patients With Advanced Solid Tumors.

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Bayer
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01439152
First received: September 1, 2011
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

BAY94-9343 is an antibody-drug conjugate (ADC) directed against the cancer antigen mesothelin on tumor cells. This study will attempt to answer the following questions:

  • What are the side effects of BAY94-9343 when given at different dose levels and schedules?
  • What dose level and schedule of BAY94-9343 should be tested in future clinical research studies?
  • How much BAY94-9343 is in the blood at specific times after administration?
  • Does the treatment with BAY94-9343 show any effect on the tumor growth?
  • Are there specific biomarkers that might be able to explain why some patients respond to treatment and others do not?

Condition Intervention Phase
Oncology
Drug: BAY94-9343
Drug: BAY94-9343 (Expansion)
Drug: BAY94-9343 (1.8 mg/kg)
Drug: BAY94-9343 (2.2 mg/kg)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Phase I Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Maximum Tolerated Dose of the Anti-mesothelin Antibody Drug Conjugate BAY94-9343 in Subjects With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Number of participants with treatment emergent adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Determination of the Pharmakokinetic profile of BAY94-9343 and its metabolites [ Time Frame: C1D1/C3D1: pre-dose, 30min, 60min, 1.5, 2, 3, 5, 8, 24, 48 and 168h after start of infusion; C2D1: pre-dose, 30min, 60min, 2, 5, 24 and 168h after start of infusion; C4, 6, 8 etc.: pre-dose and immediately after the end of infusion on D1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Biomarker evaluation: mesothelin plasma and Cytokeratin 18 (CK18) levels [ Time Frame: C1D1: pre-dose, 24, 48, and 168h after start of infusion; C2D1: pre-dose, 4 and 168h after start of infusion; C3D1: pre-dose, 24, 48, and 168h after start of infusion; C4 and every even cycle: pre-dose ] [ Designated as safety issue: No ]
  • Tumor response: assessment of best response, TTP (time to progression), and PFS (progression free survival) according to RECIST (Response Evaluation Criteria in Solid Tumours) 1.1 [ Time Frame: 1 year/Screening; Within 5 days before the end of every even cycle until Cycle 8 (Cycle 2, Cycle 4, etc.); Within 5 days before the end of every 4th cycle after Cycle 8 (Cycle 12, 16, etc.); end of treatment ] [ Designated as safety issue: No ]
  • Immunogenicity assessment: assessment of anti BAY 94-9343 antibodies [ Time Frame: 1 year / Cycle 1, 2 and 3 Day 1: pre-dose; Day 1 of every even cycle starting from Cycle 4 (Cycle 4, 6, 8 etc.): pre-dose ] [ Designated as safety issue: No ]
  • Biomarker evaluation - Levels of mesothelin expression in tumor tissue [ Time Frame: Anytime prior to general screening ] [ Designated as safety issue: No ]

Estimated Enrollment: 141
Study Start Date: September 2011
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BAY94-9343 (Dose-Escalation)
ENROLLMENT CLOSED
Drug: BAY94-9343
BAY94-9343 will be administered intravenously in this study. The starting dose for this first-in-man study is 0.15 mg/kg administered as a 1 hour infusion every 21 days.
Experimental: BAY94-9343 (Expansion)
After Maximum tolerated dose (MTD) has been defined, expansion cohorts will be conducted at the MTD dose. Overall up to 32 subjects are planned to be enrolled in the expansion cohort: - Ovarian Carcinoma, 20 subjects - Mesothelioma, 6-12 subjects (ENROLLMENT CLOSED)
Drug: BAY94-9343 (Expansion)
BAY94-9343 will be administered intravenously in this study. The dose for this expansion cohort is 5.5mg/kg administered as a 1 hour infusion every 21 days
Experimental: BAY94-9343 (1.8 mg/kg)
This part of study will be randomized and open-label. BAY94-9343 in two parallel dose cohorts of twenty (20) patients with recurrent platinum-resistant or platinum partially-sensitive ovarian cancer and up to four (4) patients with advanced malignant epithelioid peritoneal mesothelioma.
Drug: BAY94-9343 (1.8 mg/kg)
BAY94-9343 will be administered intravenously in this study. The dose for this cohort is 1.8 mg/kg administered as a 1 hour infusion every week for 3 weeks.
Experimental: BAY94-9343 (2.2 mg/kg)
This part of study will be randomized and open-label. BAY94-9343 in two parallel dose cohorts of twenty (20) patients with recurrent platinum-resistant or platinum partially-sensitive ovarian cancer and up to four (4) patients with advanced malignant epithelioid peritoneal mesothelioma.
Drug: BAY94-9343 (2.2 mg/kg)
BAY94-9343 will be administered intravenously in this study. The dose for this cohort is 2.2 mg/kg administered as a 1 hour infusion every week for 3 weeks.

  Eligibility

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

Inclusion Criteria:

  • All subjects must be ≥ 18 years at the first screening examination / visit
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
  • Life expectancy of at least 12 weeks
  • Histologically or cytologically documented invasive epithelial ovarian, primary peritoneal, or fallopian tube cancer (tumors with pseudomyxomatous or mucinous histology are excluded) or advanced predominantly epithelioid peritoneal mesothelioma.

    -- Ovarian cancer must have relapsed >0 months and ≤ 12 months of the prior platinum-based chemotherapy regimen (platinum resistant and partially platinum sensitive).

  • All patients must provide the tumor tissue sample [Formalin Fixed Paraffin Embedded (FFPE) slides] from archival tissue or fresh biopsy collected any time before the general screening under the separate informed consent.
  • Mesothelin expression in the tumor tissue from archival or fresh biopsy samples defined as the membrane intensity score of 2+ or 3+ (on the 0-3 scale) expressed on at least 30% of tumor cells.

    -- Mesothelin expression must be determined by the validated Investigational Use Only (IUO) assay for ovarian cancer or the prototype immunohistochemistry (IHC) assay for mesothelioma at Ventana at any time before the general screening in patients who had signed a separate informed consent for tumor tissue analysis for mesothelin expression.

  • No more than 3 prior lines of systemic cytotoxic therapy for patients with advanced peritoneal or pleural mesothelioma
  • No more than 5 prior lines of systemic cytotoxic therapy for patients with ovarian cancer
  • Possible intraperitoneal administration of cytotoxics during surgery will not count as systemic cytotoxic therapy in either case.
  • Measurable disease with at least one lesion that can be accurately measured in at least one dimension according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

exclusion Criteria:

  • - More than 3 prior lines of systemic cytotoxic therapy for patients with advanced peritoneal or pleural mesothelioma
  • More than 5 prior lines of systemic cytotoxic therapy for patients with ovarian cancer
  • Other systemic anticancer therapies (molecular-targeted, immunotherapy etc.) may be acceptable after the consultation between the Investigator and the Bayer Medical Expert.
  • Intraperitoneal administration of cytotoxic anticancer agents during tumor surgery will not count as systemic cytotoxic therapy in this context.
  • Prior local radiotherapy is allowed if it is completed at least 4 weeks prior to the first dose of study drug and the subject has evaluable lesions not previously irradiated.
  • Anticancer chemotherapy, experimental cancer therapy, or immunotherapy within 2 weeks of start of first dose. Anticancer therapy is defined as any agent or combination of agents with clinically proven anti tumor activity administered by any route with the purpose of affecting the malignancy, either directly or indirectly, including palliative and therapeutic endpoints.
  • Radiotherapy to the target lesions within 4 weeks prior to the first BAY94-9343 infusion, if the subject has evaluable tumor lesions not previously irradiated.
  • Use of strong inhibitors of P-glycoprotein (transporter) (P-gp) (e.g., ritonavir, cyclosporine, verapamil, and dronedarone) is prohibited from Day -14 and for the duration of the study.
  • Impaired cardiac function or clinically significant cardiac disease [i.e., congestive heart failure (CHF) New York Heart Association (NYHA) Class III or IV].
  • Left ventriculat ejection fraction (LVEF) <50 % [as measured at screening by Multiple Gated Acquisition scan (MUGA) or echocardiogram].
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 90 mmHg, despite optimal medical management.
  • Mild blurry vision, either age-related or due to ocular or systemic disorder (e.g. diabetes, dry eyes, cataracts, uncorrected refraction abnormality) may be allowed at the discretion of the ophthalmologist if deemed as no constituting a predisposition to drug-induced corneal deposits and blurry vision.
  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: NCT01439152

Contacts
Contact: Bayer Clinical Trials Contact clinical-trials-contact@bayerhealthcare.com
Contact: For trial location information (Phone Menu Options '3' or '4') (+)1-888-84 22937

Locations
United States, Connecticut
Not yet recruiting
New Haven, Connecticut, United States, 06520-8063
United States, Illinois
Not yet recruiting
Chicago, Illinois, United States, 60637
United States, Maryland
Recruiting
Bethesda, Maryland, United States, 20892
United States, Michigan
Not yet recruiting
Detroit, Michigan, United States, 48201
United States, Oklahoma
Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Not yet recruiting
Dallas, Texas, United States, 75246
Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01439152     History of Changes
Obsolete Identifiers: NCT01479335
Other Study ID Numbers: 15051
Study First Received: September 1, 2011
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Oncology
solid tumors
Antibody drug conjugate
Maximum tolerable dose
mesothelin

ClinicalTrials.gov processed this record on July 23, 2014