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Trial record 5 of 23 for:    cancer | Studies received from 04/22/2016 to 04/22/2016

Phase Ib Study of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin in Patients With Recurrent Mesothelin-expressing Platinum-resistant Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Bayer
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT02751918
First received: April 22, 2016
Last updated: March 16, 2017
Last verified: March 2017
  Purpose
Anetumab ravtansine is developed for the treatment of patients with recurrent platinum-resistant ovarian cancer. The purpose of the proposed trial is to identify the maximum tolerated dose of anetumab ravtansine that could be safely combined with pegylated liposomal doxorubicin in this indication.

Condition Intervention Phase
Ovarian Neoplasms
Drug: Anetumab ravtansine (BAY94-9343)
Drug: Pegylated Liposomal Doxorubicin
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: An Open-label Phase Ib Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Maximum Tolerated Dose of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin 30 mg/m2 Given Every 3 Weeks in Subjects With Mesothelin-expressing Platinum-resistant Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of Anetumab ravtansine in combination with pegylated liposomal doxorubicin (at 30 mg/m2 of body surface area) when given every three weeks [ Time Frame: Up to 6 months, minimum: 1 cycle (=21days) ]
    MTD is defined as the highest dose of anetumab ravtansine administered in combination with pegylated liposomal doxorubicin (at 30 mg/m2 of body surface area) that can be given such that not more than 1 of 6 subjects at a given dose level experiences a dose-limiting toxicity (DLT).

  • Incidence of serious and non-serious adverse events (AEs) [ Time Frame: Up to 6 months ]

Secondary Outcome Measures:
  • AUC (area under the plasma concentration vs. time curve from zero to infinity after single (first) dose) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me) [ Time Frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h post-dose, beginning on day 1 of cycle 1 ]
  • AUC(0-tlast) (AUC from time zero to the last data point > lower limit of quantification) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me) [ Time Frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h post-dose, beginning on day 1 of cycle 1 ]
  • Cmax (maximum drug concentration in plasma after first dose administration) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me) [ Time Frame: At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h post-dose, beginning on day 1 of cycle 1 ]
  • AUC of total pegylated liposomal doxorubicin [ Time Frame: At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose , beginning on day 1 of cycle 1 ]
  • AUC(0-tlast) of total pegylated liposomal doxorubicin [ Time Frame: At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose , beginning on day 1 of cycle 1 ]
  • Cmax of total pegylated liposomal doxorubicin [ Time Frame: At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose, beginning on day 1 of cycle 1 ]
  • Incidence of patients with CR, PR, SD or PD according to RECIST 1.1 [ Time Frame: Up to 17 months or until discontinuation of study, whichever comes first ]
    CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease)

  • Incidence of positive anti-drug antibody titer [ Time Frame: Up to 17 months or until discontinuation of study, whichever comes first ]
  • Incidence of positive neutralizing antibody titer [ Time Frame: Up to 17 months or until discontinuation of study, whichever comes first ]

Estimated Enrollment: 40
Actual Study Start Date: June 8, 2016
Estimated Study Completion Date: June 1, 2018
Estimated Primary Completion Date: February 28, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anetumab ravtansine
Anetumab ravtansine in combination with pegylated liposomal doxorubicin 30 mg/m2 of body surface area in subjects with mesothelin-expressing platinum-resistant recurrent ovarian, fallopian tube, or primary peritoneal cancer. Increase/Decrease of Anetumab ravtansine until maximum tolerated dose identified.
Drug: Anetumab ravtansine (BAY94-9343)
Anetumab ravtansine will be administered by 1-hour IV infusion on Day 1 of every 21-day treatment cycle. The starting dose of anetumab ravtansine in the first dose cohort in Part 1 will be 5.5 mg/kg of body weight.
Drug: Pegylated Liposomal Doxorubicin
Pegylated liposomal doxoribicin will be administered by 1-hour IV infusion on Day 1 of every 21-day treatment cycle at a dosage of 30 mg/m2 of body surface area. Application will be after anetumab ravtansine infusion.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject must provide a signed informed consent before any screening procedures.
  • Subject must be female and aged ≥18 years.
  • Subject must have histologically confirmed, locally invasive or metastatic, predominantly epithelial platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer.
  • Subject must have recurrent, platinum-resistant cancer
  • Subjects must provide samples of archival tumor tissue (tissue block or at least 5 formalin-fixated, paraffin-embedded [FFPE] slides) at any time during the study.
  • Subject must have a life expectancy of at least 12 weeks.
  • Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Subject must have adequate bone marrow, kidney and liver function and coagulation, as assessed by the standard laboratory test results
  • Women of reproductive potential must have a negative serum beta human chorionic gonadotropin (beta HCG) pregnancy test obtained within 7 days before the start of anetumab ravtansine. Women not of reproductive potential are female subjects who are postmenopausal or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy).
  • Women of reproductive potential must agree to consistently use adequate contraception / birth control between signing of the informed consent and 60 days after the last administration of the last study drug. The investigator or a designated associate should advise the subject how to achieve adequate contraception. Due to the lack of adequate reproductive toxicity data on anetumab ravtansine, subjects must concomitantly use 2 forms of adequate contraception.

Exclusion Criteria:

  • Subjects who have a previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study.
  • Subjects who have a history or current evidence of bleeding disorder within 4 weeks before the start of anetumab ravtansine.
  • Subjects who have new or progressive brain or meningeal or spinal metastases.
  • Subjects who have QTc (QT interval corrected for heart rate) >480 ms, or heart rate >/=100 bpm, or LVEF (left ventricular ejection fraction) <50%, or a history or current evidence of uncontrolled cardiovascular disease.
  • Women who are pregnant or breastfeeding.
  • Subjects who had a major surgery or significant trauma within 4 weeks before the start of anetumab ravtansine.
  • Subjects who have had organ allograft or hematopoietic transplantation.
  • Subjects who have a history of hypersensitivity to any of the study drugs, or any other antigen.
  • Subjects who have a history of human immunodeficiency virus (HIV) infection, or an active hepatitis B or C virus infection requiring treatment.
  • Subjects with a non-healing serious wound, ulcer, or bone fracture unrelated to the primary tumor.
  • Subjects with corneal epitheliopathy or any eye disorder that may predispose the subjects to drug-induced corneal epitheliopathy.
  • Subjects who have received systemic antitumor therapy or radiotherapy to target lesions within 4 weeks before the start of anetumab ravtansine
  • Subjects who have unresolved CTCAE (Common Terminology Criteria for Adverse Events, v4.03) Grade >1 toxicity of previous anticancer therapy.
  • Subjects who have received G-CSF (granulocyte colony-stimulating factor(s)), or GM-CSF (granulocyte macrophage-stimulating factor(s)), or erythropoietin-stimulating agents within 3 weeks before the start of screening.
  • Subjects who have received chemotherapy with anthracycline agents at the cumulative dose of 550 mg/m2.
  • Subjects who have received any investigational drug treatment outside of this study within 4 weeks before the start of anetumab ravtansine.
  • Use of strong CYP3A4 inhibitors or strong CYP3A4 inducers oral or parenteral anticoagulation therapy started within 2 weeks before the start of anetumab ravtansine until the EoT (end of treatment) visit.
  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: NCT02751918

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
Recruiting
New Haven, Connecticut, United States, 06520-8064
United States, Oklahoma
Recruiting
Oklahoma City, Oklahoma, United States, 73104
Moldova, Republic of
Recruiting
Chisinau, Moldova, Republic of, 2025
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02751918     History of Changes
Other Study ID Numbers: 18326
Study First Received: April 22, 2016
Last Updated: March 16, 2017

Keywords provided by Bayer:
Mesothelin-expressing platinum-resistant cancer

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Endocrine System Diseases
Gonadal Disorders
Doxorubicin
Liposomal doxorubicin
Maytansine
Immunoconjugates
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 27, 2017