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Metastatic Breast CancerPhase 1/2NCT03411161

S 81694 Plus Paclitaxel in Metastatic Breast Cancer

A Phase 1/2 study testing Combination therapy (S81694 + paclitaxel) phase I, Paclitaxel and Combination therapy (S81694 + paclitaxel) phase II in people with Metastatic Breast Cancer and Metastatic Triple Negative Breast Cancer, run by Institut de Recherches Internationales Servier at 6 sites in 4 countries.

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

The purpose of this study is to determine the safety profile, the maximum tolerated dose (MTD) and the associated dose-limiting toxicities (DLTs) of S 81694 in combination with paclitaxel in metastatic breast cancer (mBC) patients, and to investigate the antitumour activity of the combination in metastatic triple… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Combination therapy (S81694 + paclitaxel) phase I, Paclitaxel and Combination therapy (S81694 + paclitaxel) phase II
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
6 sitesin 4 countries
Study dates
4 Jan 2018to 8 Jun 2020
Phase
Phase 1/2
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

  • For Phase I :
  • Histologically or cytologically confirmed metastatic breast cancer, refractory to any standard therapy or for which the standard therapy is considered unsuitable;
  • Patient must have at least one evaluable or measurable metastatic lesion (lesions as defined by revised Response Evaluation Criteria in Solid Tumors).
  • For Phase II :
  • Histologically or cytologically confirmed advanced inoperable triple negative breast cancer with no prior anticancer therapy regimen in metastatic setting;
  • Patient with a minimum washout period of 12 months following previous taxane based adjuvant therapy;
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  • Patient must have at least one measurable metastatic lesion. Ascites, pleural effusion, and bone metastases are not considered measurable;
  • Acceptance of pre-treatment metastatic biopsies for all patients and on-treatment metastatic biopsies in selected centres.
  • For the whole study:
  • Male or female subjects aged ≥ 18 years old, or legal age of the majority in the country;
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
  • Estimated life expectancy of at least 3 months;
  • Adequate haematological function based on the last assessment performed within 7 days prior to the first IMP (investigational medicinal product) administration;
  • Adequate renal function based on the last assessment performed within 7 days prior to the first IMP administration;
  • Adequate hepatic function based on the last assessment performed within 7 days prior to the first IMP administration;
  • Female participant of childbearing potential must have a negative pregnancy test (serum) within 7 days prior to the first day of test drug administration. Effective contraception both for female patients of childbearing potential and male patients with parteners of childbearing potential.

Who cannot join

  • Other active malignancy within the last 3 years (except for basal cell carcinoma or a non-invasive/in situ cervical cancer or intra-mucosal gastro-intestinal cancers that were treated curatively);
  • Presence of grade ≥ 2 toxic effects (excluding alopecia) due to prior cancer therapy;
  • Known hypersensitivity to the IMP (S 81694 and paclitaxel) or their excipients;
  • Evidence of peripheral neuropathy of grade 2 or higher;
  • Participant previously received paclitaxel and discontinued due to toxicity related to paclitaxel;
  • Participant known as refractory to taxanes;
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  • Any prior cancer therapy within 4 weeks or 5 half-life (whichever is the shorter) before the first IMP administration;
  • Participant with current, serious, uncontrolled infections;
  • Participant with brain metastasis or leptomeningeal metastasis (except patients with brain metastasis that have been stable post-radiation therapy and who are off steroids for > 2 months);
  • History of cardiac disease;
  • Uncontrolled arterial hypertension;
  • Presence of risk factors for torsades de pointes (e.g. heart failure, hypokalaemia, family history of long QT syndrome);
  • Any clinically significant medical condition (e.g. organ dysfunction) or laboratory abnormality likely to jeopardize the patient's safety or to interfere with the conduct of the study, in the investigator's opinion.

Trial locations and contacts

6 sites in 4 countries.

6 sites in 4 countries

Belgium2 sites
  • Institut Jules Bordet Clinique Oncologie Médicale

    Brussels, 1000

  • UZ Leuven Campus Gasthuisberg Dept. of General Medical

    Leuven, 3000

Other trials in Belgium

Japan2 sites
  • Chiba cancer center Breast surgery

    Chiba, 2608717

  • Osaka International Cancer Institute

    Osaka, 5418567

Other trials in Japan

France1 site
  • Institut de Cancérologie de l'Ouest site Saint Herblain

    Saint-Herblain, 44805

Other trials in France

Netherlands1 site
  • Erasmus MC Section Clinical Pharmacology

    Rotterdam, 30145

Other trials in Netherlands

About this study

Official title: Phase I/II Trial of S 81694 Administered Intravenously in Combination With Paclitaxel to Evaluate the Safety, Pharmacokinetic and Efficacy in Metastatic Breast Cancer

The purpose of this study is to determine the safety profile, the maximum tolerated dose (MTD) and the associated dose-limiting toxicities (DLTs) of S 81694 in combination with paclitaxel in metastatic breast cancer (mBC) patients, and to investigate the antitumour activity of the combination in metastatic triple negative breast cancer (mTNBC) patients.

Being tested
Combination therapy (S81694 + paclitaxel) phase I, Paclitaxel, Combination therapy (S81694 + paclitaxel) phase II
Keywords
Mps1, Mps1i, S81694, breast cancer, triple negative breast cancer, phase I, phase II
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms, Mucopolysaccharidosis I

What participants receive

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

  • Combination therapy (S81694 + paclitaxel) phase IDrug

    Dose escalation S 81694 (IV); paclitaxel started at 80 mg/m²,(IV)

  • PaclitaxelDrug

    Paclitaxel (IV) at 80 mg/m²/week

  • Combination therapy (S81694 + paclitaxel) phase IIDrug

    S 81694 (IV) at RP2D; paclitaxel (IV) at 80 mg/m²/week

Study groups in NCT03411161
Study groupRoleWhat they receive
Combination therapy (S81694 + paclitaxel) phase IExperimentalPhase I: Single arm, non-randomized study in metastatic breast cancer patients. S81694 given intravenously every two weeks at different doses on D1 and D15 last for 28 days. The participants will also receive paclitaxel intravenously on D1, D8 and D15 last for 28 days.
Receives: Drug: Combination therapy (S81694 + paclitaxel) phase I
paclitaxel phase IIActive comparatorPhase II: Randomised phase II part , two-arm, in untreated metastatic triple negative breast cancer patients. Paclitaxel given intravenously on D1, D8, and D15 at 80 mg/m² during a 28-day cycle.
Receives: Drug: Paclitaxel
Combination therapy (S81694 + paclitaxel) phase IIExperimentalPhase II: Randomised phase II part , two-arm, in untreated metastatic triple negative breast cancer patients. S 81694 given intravenously on D1 and D15 at recommended phase 2 dose (RP2D). Paclitaxel given intravenously on D1, D8, and D15 during a 28-day cycle.
Receives: Drug: Combination therapy (S81694 + paclitaxel) phase II

What is being measured

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

  1. Incidence of DLTs (dose-limiting toxicities)

    Safety criterion - A DLT is defined as any toxicity attributable to S81694 or the combination that occurs before the end of Cycle 1

    Measured: Through study completion, an average of 4 years

  2. Safety and tolerability assessed by incidence of Adverse Events

    Safety and tolerability criteria - Incidence of treatment-emergent adverse events (AEs) graded according to NCI CTCAE v4.03

    Measured: Through study completion, an average of 4 years

  3. Abnormalities in laboratory tests (haematology, blood biochemistry and urinalysis)

    Safety and tolerability criteria disease progression according to RECIST v1.1 or death due to any cause

    Measured: Through study completion, an average of 4 years

  4. Abnormalities in physical examination and performance status (ECG) (mm/s)

    Safety and tolerability criteria

    Measured: Through study completion, an average of 4 years

  5. Abnormalities in blood pressure (mmHg)

    Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment

    Measured: Through study completion, an average of 4 years

  6. Abnormalities in heart rate (BPM (beat per minute))

    Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment

    Measured: Through study completion, an average of 4 years

  7. Abnormalities in body temperature (C°degree celsius)

    Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment

    Measured: Through study completion, an average of 4 years

  8. Abnormalities in respiration rate (cycles per minute)

    Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment

    Measured: Through study completion, an average of 4 years

  9. Abnormalities in body weight (Kg)

    Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment

    Measured: Through study completion, an average of 4 years

  10. Progression free survival (PFS) [based on Investigator review of the images according to RECIST 1.1]

    Efficacy criterion - time from the date of first study drug intake until the date of the investigator-assessed disease progression or death due to any cause whichever occurs first.

    Measured: Through study completion, an average of 4 years

Secondary outcomes (6)
  1. The PK (pharmacokinetic) profile of S 81694 and paclitaxel plasma concentration : Area under the plasma concentration-time curve (AUC)

    Safety and tolerability criteria

    Measured: Through study completion, an average of 3 years

  2. The PK profile of S 81694 and paclitaxel plasma concentration : Elimination half-life (T½)

    Safety and tolerability criteria

    Measured: Through study completion, an average of 3 years

  3. The PK profile of S 81694 and paclitaxel plasma concentration : Maximum plasma concentration (Cmax)

    Safety and tolerability criteria

    Measured: Through study completion, an average of 3 years

  4. The PK profile of S 81694 and paclitaxel plasma concentration : Minimum plasma concentration (Cmin)

    Safety and tolerability criteria

    Measured: Through study completion, an average of 3 years

  5. Overall Response Rate (ORR) [ based on Investigator review of the images according to RECIST 1.1]

    Efficacy criterion

    Measured: Through study completion, an average of 4 years

  6. Incidence of treatment-emergent adverse events (AEs) graded according to NCI CTCAE v4.03

    Safety criterion

    Measured: Through study completion, an average of 4 years

Timeline

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

  1. First posted26 Jan 2018
  2. Study start4 Jan 2018
  3. Primary completion8 Jun 2020
  4. Study completion8 Jun 2020

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
This study will be conducted in two successive parts: * a dose escalation phase I part, which is a single arm, non-randomised and non-comparative study in patient with mBC * a randomised phase II part, which is a two-arm, randomised study at RP2D (recommended phase II dose), to evaluate the efficacy and the safety of S 81694 in combination with paclitaxel (experimental arm) versus paclitaxel alone (comparator arm) in untreated mTNBC
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03411161
Sponsor's protocol ID
CL1-81694-003
Other IDs
2017-002459-27, 2017
Status last verified
May 2021
First submitted
13 Dec 2017
Last updated
25 May 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Combination therapy (S81694 + paclitaxel) phase I, Paclitaxel and Combination therapy (S81694 + paclitaxel) phase II in people with Metastatic Breast Cancer and Metastatic Triple Negative Breast Cancer, run by Institut de Recherches Internationales Servier 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 16 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: finished, as of the sponsor's last update on 25 May 2021. 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 Belgium, Japan, France, Netherlands. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 DLTs (dose-limiting toxicities) (time frame: Through study completion, an average of 4 years). The study lists 10 primary outcomes in all. 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 25 May 2021.

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