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

ID: NCT02751918
Status: Recruiting
Phase: Phase 1
Start Date: June 08, 2016
First Submitted: April 22, 2016
Last Updated: February 22, 2018
Results: N/A
Organization: Bayer
Sponsors & Collaborators: Bayer
Location: Belgium, Moldova, Republic of, Spain, United States
Conditions: Ovarian Neoplasms
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Study Description

Brief Summary

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.

Detailed Description

Condition or disease Intervention/treatment Phase

Ovarian Neoplasms

Drug: Anetumab ravtansine (BAY94-9343)
Other Names
Drug: Pegylated Liposomal Doxorubicin
Other Names
Phase 1

Tracking Information

First Submitted DateApril 22, 2016
Last Update Posted DateFebruary 22, 2018
Actual Start DateJune 08, 2016
Anticipated Completion DateSeptember 14, 2019
Actual Primary Completion DateAugust 17, 2019
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

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

  • 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).

Original Primary Outcome Measures

Not Available

Current 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]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitlePhase Ib Study of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin in Patients With Recurrent Mesothelin-expressing Platinum-resistant Cancer
Official TitleAn 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
Brief Summary

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.

Detailed Description

Study TypeInterventional
Study PhasePhase 1
Estimated Enrollment
61
Allocation
Not Available
Interventional Model
Single Group Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Ovarian Neoplasms
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
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.

Other Names
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.

Other Names
Study Groups/Cohorts
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.

Study Arms
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.

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 : 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.

Arm Intervention/Treatment
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)
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 : Pegylated Liposomal Doxorubicin

Recruitment Information

Recruitment Status:Recruiting
Enrollment61
Completion DateSeptember 14, 2019
Eligibility 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 (for subjects in Parts 1 and 2, tissue block or at least 5 formalin-fixated, paraffin-embedded [FFPE] slides; for subjects in Part 3, tissue block or at least 8 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 2 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 metTumor mesothelin expression astases.
- 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 with known 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.
GenderFemale
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Belgium
Moldova, Republic of
Spain
United States

Administrative Information

NCT Number:NCT02751918
Other Study ID Numbers
18326
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Bayer
Collaborators
Not Available
Investigators
Study Director
Bayer Study Director
Bayer