CancerPhase 1NCT02317419
A Study of RO6927005 Either As Monotherapy (Part A) or in Combination With Gemcitabine and Nab-Paclitaxel (Part B) to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Clinical Activity in Patients With Mesothelin-positive Metastatic and/or Locally Advanced Malignant Solid Tumors
A Phase 1 study testing RO6927005, gemcitabine and nab-paclitaxel in people with Cancer, run by Hoffmann-La Roche at 6 sites in 4 countries.
Trial summary
This is a first-in-human, open-label, multi-center, Phase 1 study of RO6927005. The study will establish the safety and tolerability profile of RO6927005 and will be conducted in two parts. In Part A, the first dose escalations will be carried out using cohorts of 1 patient. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- RO6927005, gemcitabine and nab-paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 6 sitesin 4 countries
- Study dates
- Dec 2014to Aug 2015
- 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
- Written informed consent
- Age >/= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
- Patients for whom no standard curable therapy exists
- Life expectancy of >/= 12 weeks
- Last dose of systemic anti-neoplastic therapy > 21 days prior to first RO6927005 infusion
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- Palliative radiotherapy is allowed up to 2 weeks before the first RO6927005 infusion; palliative 8 Gy radiotherapy is allowed during therapy.
- All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade </= 1, except alopecia (any grade) and Grade 2 peripheral neuropathy
- Adequate hematological, liver, and renal function
- Negative serum or urine pregnancy test within 7 days prior to study treatment in premenopausal women and women </= 2 years after menopause (menopause is defined as amenorrhea for >/= 2 years)
- Agreement to use adequate contraceptive methods per protocol
- Measurable and/or evaluable disease as per the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1) [Groups 1, 2 of Part A and Group 3 of Part B]
- Metastatic and/or locally advanced malignant solid tumors enriched in tumor types known to be mesothelin expressing
- Archival sample or fresh biopsy or tumor effusion must be available for retrospective mesothelin analysis
- Inclusion Criteria Part A: MAD and Extension Phase (Group 1 and Group 2)
- Histologically confirmed metastatic and/or advanced malignant mesothelin-positive solid tumors as determined by central pathology lab review
- Patients must be willing to provide a screening and post-dose biopsy for biomarker analysis (extension phase only)
- Mesothelin-positive refractory/recurrent solid tumors, other than malignant pleural mesothelioma (MPM) and pancreatic ductal adenocarcinoma (PDA) (Group 1 only)
- Mesothelin-positive refractory/recurrent MPM (Group 2 only)
- Histologically confirmed metastatic and/or advanced mesothelin-positive PDA as determined by central pathology lab review
- In the extension phase, patients must be willing to provide a screening and post-dose biopsy for biomarker analysis
Who cannot join
- Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days
- Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results, including significant pulmonary disease other than primary cancer, uncontrolled diabetes mellitus, and/or significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, unstable angina, or clinically significant pericardial effusion)
- Active or uncontrolled infections
- Known HIV or known active HBV or HCV infection
- Patients with extrapleural pneumonectomy (EPP)
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
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- Major surgery or significant traumatic injury < 28 days prior to the first RO6927005 infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
- Dementia or altered mental status that would prohibit informed consent
- Live attenuated vaccinations 14 days prior to treatment
- Pregnant or breast-feeding women
- Known hypersensitivity to any of the components of RO6927005
- High doses of systemic corticosteroids within 7 days prior to first dosing. High dose is considered as > 20 mg of dexamethasone a day (or equivalent) for > 7 consecutive days
- Patients with contra-indication and/or history of severe hypersensitivity reactions to gemcitabine and/or nab-paclitaxel as mentioned in the locally approved label
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
France3 sites
Study site
Bordeaux, 33076
Study site
Toulouse, 31059
Study site
Villejuif, 94805
About this study
Official title: PHASE IA/IB, OPEN-LABEL, MULTICENTER, MULTIPLE ASCENDING DOSE STUDY FOLLOWED BY AN EXTENSION PHASE TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND ACTIVITY OF RO6927005, AN ANTI-MESOTHELIN (MSLN) RECOMBINANT CYTOLYTIC FUSION PROTEIN (cFP), ADMINISTERED EITHER ALONE (PART A) OR IN COMBINATION WITH GEMCITABINE AND NAB-PACLITAXEL (PART B) IN PATIENTS WITH MESOTHELIN-POSITIVE METASTATIC AND/OR LOCALLY ADVANCED MALIGNANT SOLID TUMORS
This is a first-in-human, open-label, multi-center, Phase 1 study of RO6927005. The study will establish the safety and tolerability profile of RO6927005 and will be conducted in two parts.
In Part A, the first dose escalations will be carried out using cohorts of 1 patient. Single patient cohorts will be used to investigate increasing doses until a first dose-limiting toxicity (DLT) is reached or until grade-2 related toxicity (except infusion-related reactions), whichever comes first. At least 3 patients will be enrolled in each cohort thereafter, which, if required, can be expanded with additional patients. Part B of the study will consist of a multiple ascending dose phase (multiple patients cohorts - >/= 3 patients) followed by an extension phase of RO6927005 given in combination with gemcitabine/nab-paclitaxel.
Preliminary clinical activity will be explored throughout the study. Patients will be treated until disease progression and/or lack of clinical benefit, unacceptable toxicities, withdrawal from treatment for other reasons, death, pregnancy or termination of the study by the Sponsor, whichever comes first.
- Conditions
- Cancer
- Being tested
- RO6927005, gemcitabine, nab-paclitaxel
- Keywords
- Solid Cancers
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RO6927005Drug
RO6927005 administered intravenously on Days 1, 3, and 5 of each 21-day treatment cycle (QOD x 3).
RO6927005Drug
RO6927005 administered intravenously on Days 1, 3, and 5 of each 28-day treatment cycle (QOD x 3).
gemcitabineDrug
gemcitabine administered according to local label on Days 1, 8, and 15 of each 28-day cycle.
nab-paclitaxelDrug
nab-paclitaxel administered according to the local label on Days 1, 8, and 15 of each 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Part A MAD Phase RO6927005 Monotherapy | Experimental | RO6927005 given as a single agent in participants with tumors known to be mesothelin expressing and with mesothelin-positive tumors. MAD = multiple ascending dose. Receives: Drug: RO6927005 |
| Part A Extension Phase Group 1 | Experimental | RO6927005 given as a single agent in participants with mesothelin-positive refractory/recurrent solid tumors, other than malignant pleural mesothelioma (MPM) and pancreatic ductal adenocarcinoma (PDA) Receives: Drug: RO6927005 |
| Part A Extension Phase Group 2 | Experimental | RO6927005 given as a single agent in participants with mesothelin-positive metastatic and/or advanced PDA Receives: Drug: RO6927005 |
| Part B MAD Phase | Experimental | RO6927005 with gemcitabine/nab-paclitaxel in participants with mesothelin-positive metastatic and/or advanced PDA Receives: Drug: RO6927005; Drug: gemcitabine; Drug: nab-paclitaxel |
| Part B Extension Phase | Experimental | RO6927005 with gemcitabine/nab-paclitaxel in participants with PDA Receives: Drug: RO6927005; Drug: gemcitabine; Drug: nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: incidence of dose-limiting toxicities, adverse events, laboratory abnormalities; incidence of anti-drug antibodies, abnormal findings on physical examination, infusion-related reactions (composite outcome measure)
Measured: Until disease progression, unacceptable toxicities, withdrawal for other reasons, death, or termination of the study by the Sponsor, whichever comes first, up to 2 years 8 months
Secondary outcomes (3)
Pharmacokinetic profile of RO6927005 monotherapy based on free and total plasma RO6927005 concentrations over time (area under the curve)
Measured: Up to 2 years 8 months
Pharmacokinetic profile of RO6927005 in combination with gemcitabine/nab-paclitaxel, based on free and total plasma RO6927005 concentrations over time (area under the curve)
Measured: Up to 2 years 8 months
Efficacy: objective response rate, disease control rate, duration of response, progression-free survival, overall survival (composite outcome measure)
Measured: Up to 2 years 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2014 (estimated)
- Study startDec 2014
- Primary completionAug 2015
- Study completionAug 2015
Why it stopped: The study was prematurely terminated because the emerging benefit:risk ratio did not justify continuing dosing patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02317419
- Sponsor's protocol ID
- BP29387
- Other IDs
- 2014-002935-32, 2014
- Status last verified
- Jul 2016
- First submitted
- 11 Dec 2014
- Last updated
- 26 Jul 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PHASE IA/IB, OPEN-LABEL, MULTICENTER, MULTIPLE ASCENDING DOSE STUDY FOLLOWED BY AN EXTENSION PHASE TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND ACTIVITY OF RO6927005, AN ANTI-MESOTHELIN (MSLN) RECOMBINANT CYTOLYTIC FUSION PROTEIN (cFP), ADMINISTERED EITHER ALONE (PART A) OR IN COMBINATION WITH GEMCITABINE AND NAB-PACLITAXEL (PART B) IN PATIENTS WITH MESOTHELIN-POSITIVE METASTATIC AND/OR LOCALLY ADVANCED MALIGNANT SOLID TUMORS
- ClinicalTrials.gov ID
- NCT02317419
- Acronym / sponsor ID
- BP29387
- Conditions
- Cancer
- Keywords
- Solid Cancers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was prematurely terminated because the emerging benefit:risk ratio did not justify continuing dosing patients.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Dec 2014
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 16 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a first-in-human, open-label, multi-center, Phase 1 study of RO6927005. The study will establish the safety and tolerability profile of RO6927005 and will be conducted in two parts.
In Part A, the first dose escalations will be carried out using cohorts of 1 patient. Single patient cohorts will be used to investigate increasing doses until a first dose-limiting toxicity (DLT) is reached or until grade-2 related toxicity (except infusion-related reactions), whichever comes first. At least 3 patients will be enrolled in each cohort thereafter, which, if required, can be expanded with additional patients. Part B of the study will consist of a multiple ascending dose phase (multiple patients cohorts - >/= 3 patients) followed by an extension phase of RO6927005 given in combination with gemcitabine/nab-paclitaxel.
Preliminary clinical activity will be explored throughout the study. Patients will be treated until disease progression and/or lack of clinical benefit, unacceptable toxicities, withdrawal from treatment for other reasons, death, pregnancy or termination of the study by the Sponsor, whichever comes first.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part A MAD Phase RO6927005 Monotherapy | Experimental | Drug: RO6927005RO6927005 given as a single agent in participants with tumors known to be mesothelin expressing and with mesothelin-positive tumors. MAD = multiple ascending dose. |
| Part A Extension Phase Group 1 | Experimental | Drug: RO6927005RO6927005 given as a single agent in participants with mesothelin-positive refractory/recurrent solid tumors, other than malignant pleural mesothelioma (MPM) and pancreatic ductal adenocarcinoma (PDA) |
| Part A Extension Phase Group 2 | Experimental | Drug: RO6927005RO6927005 given as a single agent in participants with mesothelin-positive metastatic and/or advanced PDA |
| Part B MAD Phase | Experimental | Drug: RO6927005, Drug: gemcitabine, Drug: nab-paclitaxelRO6927005 with gemcitabine/nab-paclitaxel in participants with mesothelin-positive metastatic and/or advanced PDA |
| Part B Extension Phase | Experimental | Drug: RO6927005, Drug: gemcitabine, Drug: nab-paclitaxelRO6927005 with gemcitabine/nab-paclitaxel in participants with PDA |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Written informed consent
- Age >/= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
- Patients for whom no standard curable therapy exists
- Life expectancy of >/= 12 weeks
Key exclusion criteria (13 listed)
- Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases; history or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days
- Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results, including significant pulmonary disease other than primary cancer, uncontrolled diabetes mellitus, and/or significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, unstable angina, or clinically significant pericardial effusion)
- Active or uncontrolled infections
- Known HIV or known active HBV or HCV infection
- Patients with extrapleural pneumonectomy (EPP)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RO6927005RO6927005 administered intravenously on Days 1, 3, and 5 of each 21-day treatment cycle (QOD x 3). | Drug | Part A Extension Phase Group 1, Part A Extension Phase Group 2, Part A MAD Phase RO6927005 Monotherapy |
| RO6927005RO6927005 administered intravenously on Days 1, 3, and 5 of each 28-day treatment cycle (QOD x 3). | Drug | Part B Extension Phase, Part B MAD Phase |
| gemcitabinegemcitabine administered according to local label on Days 1, 8, and 15 of each 28-day cycle. | Drug | Part B Extension Phase, Part B MAD Phase |
| nab-paclitaxelnab-paclitaxel administered according to the local label on Days 1, 8, and 15 of each 28-day cycle. | Drug | Part B Extension Phase, Part B MAD Phase |
Primary outcome
Safety: incidence of dose-limiting toxicities, adverse events, laboratory abnormalities; incidence of anti-drug antibodies, abnormal findings on physical examination, infusion-related reactions (composite outcome measure)
Time frame: Until disease progression, unacceptable toxicities, withdrawal for other reasons, death, or termination of the study by the Sponsor, whichever comes first, up to 2 years 8 months
3 secondary outcomes
Pharmacokinetic profile of RO6927005 monotherapy based on free and total plasma RO6927005 concentrations over time (area under the curve)
Time frame: Up to 2 years 8 months
Pharmacokinetic profile of RO6927005 in combination with gemcitabine/nab-paclitaxel, based on free and total plasma RO6927005 concentrations over time (area under the curve)
Time frame: Up to 2 years 8 months
Efficacy: objective response rate, disease control rate, duration of response, progression-free survival, overall survival (composite outcome measure)
Time frame: Up to 2 years 8 months
Results and safety
The study was stopped early (reason given: The study was prematurely terminated because the emerging benefit:risk ratio did not justify continuing dosing patients.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RO6927005, gemcitabine and nab-paclitaxel in people with Cancer, run by Hoffmann-La Roche at 6 sites in 4 countries.
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 21 inclusion and 13 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: stopped early, as of the sponsor's last update on 26 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in France, United States, Canada, Denmark. 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 was stopped early (reason given: The study was prematurely terminated because the emerging benefit:risk ratio did not justify continuing dosing patients.). Results are not available in the source record.
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?
Safety: incidence of dose-limiting toxicities, adverse events, laboratory abnormalities; incidence of anti-drug antibodies, abnormal findings on physical examination, infusion-related reactions (composite outcome measure) (time frame: Until disease progression, unacceptable toxicities, withdrawal for other reasons, death, or termination of the study by the Sponsor, whichever comes first, up to 2 years 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Jul 2016; AzTrials last refreshed its copy on 6 Nov 2026.