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OncologyPhase 1NCT01439152

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

A Phase 1 study testing BAY94-9343, BAY94-9343 (Expansion) and BAY94-9343 (1.8 mg/kg) in people with Oncology, run by Bayer at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

BAY94-9343 was an antibody-drug conjugate (ADC) directed against the cancer antigen mesothelin on tumor cells. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Oncology
What is being tested?
BAY94-9343, BAY94-9343 (Expansion) and BAY94-9343 (1.8 mg/kg)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
148 participants
Where
8 sitesUnited States
Study dates
7 Sep 2011to 30 Jul 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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 or
  • 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.

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Study site

    Bethesda, Maryland, 20892

  • Study site

    Chicago, Illinois, 60637

  • Study site

    Dallas, Texas, 75251

  • Study site

    Detroit, Michigan, 48201

  • Study site

    Houston, Texas, 77030

  • Study site

    Nashville, Tennessee, 37203

  • Study site

    New Haven, Connecticut, 06520-8063

  • Study site

    Oklahoma City, Oklahoma, 73104

Other trials in United States

About this study

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

BAY94-9343 was an antibody-drug conjugate (ADC) directed against the cancer antigen mesothelin on tumor cells.

Conditions
Oncology
Being tested
BAY94-9343, BAY94-9343 (Expansion), BAY94-9343 (1.8 mg/kg), BAY94-9343 (2.2 mg/kg)
Keywords
Oncology, Solid tumors, Antibody drug conjugate (ADC), Treatment Emergent Adverse Events, Mesothelin
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BAY94-9343Drug

    BAY94-9343 was administered intravenously in this study. The starting dose for this first-in-man study was 0.15 mg/kg administered as a 1 hour infusion every 21 days.

  • BAY94-9343 (Expansion)Drug

    BAY94-9343 was administered intravenously in this study. The dose for this expansion cohort was 5.5mg/kg administered as a 1 hour infusion every 21 days.

  • BAY94-9343 (1.8 mg/kg)Drug

    BAY94-9343 was administered intravenously in this study. The dose for this cohort was 1.8 mg/kg administered as a 1 hour infusion every week for 3 weeks.

  • BAY94-9343 (2.2 mg/kg)Drug

    BAY94-9343 was administered intravenously in this study. The dose for this cohort was 2.2 mg/kg administered as a 1 hour infusion every week for 3 weeks.

Study groups in NCT01439152
Study groupRoleWhat they receive
BAY94-9343 (Dose-Escalation)ExperimentalBAY94-9343 was administered intravenously in this study. The starting dose for this first-in-man study was 0.15 mg/kg administered as a 1 hour infusion every 21 days. (ENROLLMENT CLOSED).
Receives: Drug: BAY94-9343
BAY94-9343 (Expansion)ExperimentalAfter Maximum tolerated dose (MTD) had been defined, expansion cohorts were conducted at the MTD dose. Overall up to 32 subjects were planned to be enrolled in the expansion cohort: * Ovarian Carcinoma, 20 subjects * Mesothelioma, 6-12 subjects (ENROLLMENT CLOSED).
Receives: Drug: BAY94-9343 (Expansion)
BAY94-9343 (1.8 mg/kg)ExperimentalThis part of study was 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 and eight (8) patients with advanced pleural mesothelioma.
Receives: Drug: BAY94-9343 (1.8 mg/kg)
BAY94-9343 (2.2 mg/kg)ExperimentalThis part of study was 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 and eight (8) patients with advanced pleural mesothelioma.
Receives: Drug: BAY94-9343 (2.2 mg/kg)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of DLT (dose limiting toxicity) of BAY 94-9343

    Measured: At the end of Cycle 1 Day21

  2. Determination of the Pharmacokinetic profile of BAY94-9343 and its metabolites (ADC, Total Antibody, DM4 and DM4-Me)

    Q3W Arm: Cmax, AUC (0-504), AUC (0-tlast), tmax, t1/2 and AUC (Cycle 1 only) Q3W: Cycle 1 and Cycle 3: pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, (24), 48, (96), 168, 336 and 504 hours after start of infusion QW Arm:Cmax, AUC(0-168) and tmax) QW: Cycle 1 and Cycle 3: pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, 24, 48 and 168 hours after start of infusion

    Measured: Cycle 1 and Cycle 3: pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, (24), 48, (96), 168, 336 and 504 hours after start of infusion

Secondary outcomes (4)

  1. Biomarker evaluation: Plasma concentrations of soluble mesothelin and Cytokeratin 18 (CK18)

    Measured: 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 until Implementation of Am 6

  2. Tumor response: assessment of best response and PFS (progression free survival) according to RECIST (Response Evaluation Criteria in Solid Tumours) 1.1

    Measured: 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

  3. Immunogenicity assessment: assessment of Anti-drug antibody (ADA) formation and neutralizing antibodies (NAs) against anetumab ravtansine

    Measured: 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 until implementation of Am 6

  4. Biomarker evaluation - Levels of mesothelin expression in tumor tissue

    Measured: Anytime prior to general screening

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2011 (estimated)
  2. Study start7 Sep 2011
  3. Primary completion31 Dec 2016
  4. Study completion30 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
148 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01439152
Sponsor's protocol ID
15051
Status last verified
Jul 2021
First submitted
1 Sep 2011
Last updated
9 Jul 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Hassan R, Blumenschein GR Jr, Moore KN, Santin AD, Kindler HL, Nemunaitis JJ, Seward SM, Thomas A, Kim SK, Rajagopalan P, Walter AO, Laurent D, Childs BH, Sarapa N, Elbi C, Bendell JC. First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody-Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors. J Clin Oncol. 2020 Jun 1;38(16):1824-1835. doi: 10.1200/JCO.19.02085. Epub 2020 Mar 26.

    PubMed 32213105

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BAY94-9343, BAY94-9343 (Expansion) and BAY94-9343 (1.8 mg/kg) in people with Oncology, run by Bayer at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of DLT (dose limiting toxicity) of BAY 94-9343 (time frame: At the end of Cycle 1 Day21). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01439152, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2021.

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