S 81694 Plus Paclitaxel in Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03411161
• Other study ID #: CL1-81694-003
• Secondary ID: 2017-002459-27
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 4, 2018
• Est. completion date: June 8, 2020

Study information

• Verified date: May 2021
• Source: Servier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 negative breast cancer (mTNBC) patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: June 8, 2020
• Est. primary completion date: June 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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;
• 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.

Exclusion Criteria:

• 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;
• 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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer
• Metastatic Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Combination therapy (S81694 + paclitaxel) phase I
Dose escalation S 81694 (IV); paclitaxel started at 80 mg/m²,(IV)
• Paclitaxel
Paclitaxel (IV) at 80 mg/m²/week
• Combination therapy (S81694 + paclitaxel) phase II
S 81694 (IV) at RP2D; paclitaxel (IV) at 80 mg/m²/week

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet Clinique Oncologie Médicale	Bruxelles
Belgium	UZ Leuven Campus Gasthuisberg Dept. of General Medical	Leuven
France	Institut de Cancérologie de l'Ouest site Saint Herblain	Saint Herblain
Japan	Chiba cancer center Breast surgery	Chiba
Japan	Osaka International Cancer Institute	Osaka
Netherlands	Erasmus MC Section Clinical Pharmacology	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Recherches Internationales Servier	ADIR, a Servier Group company

Countries where clinical trial is conducted

Belgium,  France,  Japan,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Through study completion, an average of 4 years
Primary	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	Through study completion, an average of 4 years
Primary	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	Through study completion, an average of 4 years
Primary	Abnormalities in physical examination and performance status (ECG) (mm/s)	Safety and tolerability criteria	Through study completion, an average of 4 years
Primary	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	Through study completion, an average of 4 years
Primary	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	Through study completion, an average of 4 years
Primary	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	Through study completion, an average of 4 years
Primary	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	Through study completion, an average of 4 years
Primary	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	Through study completion, an average of 4 years
Primary	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.	Through study completion, an average of 4 years
Secondary	The PK (pharmacokinetic) profile of S 81694 and paclitaxel plasma concentration : Area under the plasma concentration-time curve (AUC)	Safety and tolerability criteria	Through study completion, an average of 3 years
Secondary	The PK profile of S 81694 and paclitaxel plasma concentration : Elimination half-life (T½)	Safety and tolerability criteria	Through study completion, an average of 3 years
Secondary	The PK profile of S 81694 and paclitaxel plasma concentration : Maximum plasma concentration (Cmax)	Safety and tolerability criteria	Through study completion, an average of 3 years
Secondary	The PK profile of S 81694 and paclitaxel plasma concentration : Minimum plasma concentration (Cmin)	Safety and tolerability criteria	Through study completion, an average of 3 years
Secondary	Overall Response Rate (ORR) [ based on Investigator review of the images according to RECIST 1.1]	Efficacy criterion	Through study completion, an average of 4 years
Secondary	Incidence of treatment-emergent adverse events (AEs) graded according to NCI CTCAE v4.03	Safety criterion	Through study completion, an average of 4 years

External Links

•   Lay Summary
•   Results Summary