Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Immune System Diseases

Breast Neoplasms

Recurrence

Hypersensitivity

Breast Diseases

Skin Diseases

Menopause

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Vaccines

Estrogens

Immunomodulating Agents

Progesterone

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Investigational Arm:

* Pretreatment (Single Dose): 300 milligrams per square meter (mg/m\^2) up to a maximum dose of 600 mg of intravenous cyclophosphamide
* tecemotide (L-BLP25) plus Hormonal Therapy (Standard Dose)

Control Arm:

* Pretreatment (Single Dose): sodium chloride (NaCl) 9 grams per liter (g/L) infusion
* Placebo plus Hormonal Therapy (Standard Dose)

Investigational Arm:

Pretreatment (Single Dose) 300 mg/m\^2 of intravenous cyclophosphamide in investigational arm to a maximum of 600 milligrams (mg).

Primary treatment phase:

Hormonal treatment plus 8 consecutive weekly subcutaneous vaccinations with tecemotide (L-BLP25) 1000 micrograms (actual delivered dose was 930 micrograms)\* (Week 1 to 8).

Maintenance treatment phase:

Hormonal treatment plus vaccinations with tecemotide (L-BLP25) 1000 micrograms (actual delivered dose was 930 micrograms)\* at six-week intervals beginning at Week 14 and continued until Progressive Disease (PD).

\*calculated as mass of lipopeptide (antigen)

Tecemotide (L-BLP25) and Hormonal Treatment

Control Arm:

Pretreatment (Single Dose) NaCl 9 g/L infusion as a substitute for cyclophosphamide.

Primary treatment phase:

Hormonal therapy plus 8 consecutive weekly subcutaneous placebo doses (Week 1 to 8).

Maintenance treatment phase:

Hormonal therapy plus placebo doses at six-week intervals beginning at Week 14 and continued until Progressive Disease (PD).

Placebo of tecemotide (L-BLP25) and Hormonal Treatment

300 mg/m\^2 (to a maximum of 600 mg) of intravenous cyclophosphamide.

cyclophosphamide

sodium chloride (NaCl)

Oscar Kashala, MD, PhD, DSc

EMD Serono has decided to permanently terminate the trial EMR 200038-010 (STRIDE) in the indication of breast cancer following the clinical hold on the investigational new drug application for tecemotide (L-BLP25).

The purpose of the study is to determine whether the addition of the experimental mucinous glycoprotein 1 (MUC1) antigen-specific cancer immunotherapy tecemotide (L-BLP25) to hormonal treatment is effective in prolonging progression-free survival in postmenopausal women with endocrine-sensitive inoperable locally advanced, recurrent or metastatic breast cancer.

STRIDE - STimulating Immune Response In aDvanced brEast Cancer

A Randomized, Double-blind, Controlled Phase III Study of Stimuvax® (L-BLP25 or BLP25 Liposome Vaccine) in Combination With Hormonal Treatment Versus Hormonal Treatment Alone for First-line Therapy of Post-menopausal Women With Estrogen Receptor (ER)-Positive and/or Progesterone Receptor (PgR)-Positive, Inoperable Locally Advanced, Recurrent, or Metastatic Breast Cancer

PFS was defined as the duration from randomization to first observation of progressive disease (PD) as confirmed by the independent radiological review or death.

OS time was defined as the time from randomization to death. Participants without event were to be censored at the last date known to be alive or at the clinical cut-off date, whichever was earlier.

Percentage of participants with objective tumor response was to be reported. An objective response (OR) was defined as a participant having a best overall response of either confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST 1.0) as assessed by independent radiological review.

Duration of response is defined as the time from the first assessment of CR or PR until the date of the first occurrence of PD, or until the date of death.

Clinical Benefit is defined as having achieved at least disease stabilization; that is participants with confirmed CR, PR, or stable disease (SD,) lasting for at least 22 weeks.

TTP is defined as the time from date of randomization to the date of radiological diagnosis of PD (censoring for death without progression).

Time to chemotherapy is defined as the time from date of randomization to the start date of chemotherapy.

FACT-B questionnaire consists of 36 questions; 7 in physical well-being (PWB); 7 in social well-being (SWB); 6 in emotional well-being (EWB); 7 in functional well-being (FWB); 9 in breast cancer subscale (BCS). Trial outcome Index (TOI) was calculated by the sum of the physical well-being (PWB), functional well-being (FWB), and breast cancer scale (BCS) subscales of FACT-B. Total score of subscores or TOI is calculated from each score of question. Higher score means better and lower score means worthier. Score range; 0-28 in PWB; 0-28 in SWB; 0-24 in EWB; 0-28 in FWB; 0-36 in BCS; 0-92 in TOI.

EQ-5D questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The optional part of the questionnaire was not applied. EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items are combined to generate health profiles. These profiles were to be converted to a continuous single index score using a one to one matching. The lowest possible score is -0.59 and the highest is 1.00. Higher scores on the EQ-5D represent a better quality of life (QoL) and lower scores on the EQ-5D represent a worst QoL.

Healthcare Resource Utilization (HRU) parameters included direct medical resources (e.g., nonscheduled procedures, unplanned hospitalization, outpatient visits), nonmedical resources (e.g., travel, paid and unpaid assistance), and occupational resources (e.g., occupational changes and concerns).

CA 15-3 is a serum marker for breast cancer which is a possible measure for immune response.

EMD Serono

Adverse event (AE): Any untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug.

Single dose of cyclophosphamide (300 milligrams per square meter \[mg/m\^2\] to a maximum of 600 mg) was administered intravenously, 3 days prior to the start of vaccination, followed by primary treatment phase in which weekly subcutaneous vaccinations with tecemotide (L-BLP25) 1000 micrograms (actual delivered dose was 930 micrograms) along with hormonal treatment were administered for 8 weeks, followed by maintenance treatment phase starting at Week 14 (6 weeks after the last dosing of the primary treatment phase), in which subcutaneous vaccinations with tecemotide (L-BLP25) 1000 micrograms (actual delivered dose was 930 micrograms) along with hormonal treatment were administered every 6 weeks until progressive disease (PD) was documented.

Tecemotide (L-BLP25) + Hormonal Therapy + Cyclophosphamide

Single dose of sodium chloride (NaCl) 9 g/L infusion as substitute for cyclophosphamide was administered intravenously, 3 days prior to the start of vaccination, followed by primary treatment phase in which weekly subcutaneous placebo doses matched to tecemotide (L-BLP25) along with hormonal therapy were administered for 8 weeks, followed by maintenance treatment phase starting at Week 14 (6 weeks after the last dosing of the primary treatment phase), in which subcutaneous placebo doses along with hormonal therapy were administered every 6 weeks until progressive disease (PD) was documented.

Placebo + Hormonal Therapy + NaCl 9 g/L

Total

Less than (<) 65 years

Greater than or equal to (>=) 65 years

Age, Customized

Sex: Female, Male

Safety population included all participants who received at least one dose of any study treatment (L-BLP25, placebo, cyclophosphamide, saline, or any of the three hormonal therapies).

Efficacy data were not analyzed as the trial was prematurely terminated following the clinical hold on the investigational new drug application for tecemotide (L-BLP25)

Merck KGaA Communication Center

Data were not collected as no independent read took place, due to low numbers: the trial was prematurely terminated following the clinical hold on the investigational new drug application for tecemotide (L-BLP25).

Progression-Free Survival (PFS)

Data were not analyzed as the trial was prematurely terminated following the clinical hold on the investigational new drug application for tecemotide (L-BLP25)

Overall Survival (OS) Time

Percentage of Participants With Objective Tumor Response

Duration of Response

Percentage of Participants With Clinical Benefit

Time to Progression (TTP)

Time to Chemotherapy

Functional Assessment of Cancer Therapy-Breast (FACT-B) Questionnaire

European Questionnaire-5 Dimensions (EQ-5D) Questionnaire

Single dose of sodium chloride (NaCl) 9g/L infusion as substitute for cyclophosphamide was administered intravenously, 3 days prior to the start of vaccination, followed by primary treatment phase in which weekly subcutaneous placebo doses matched to tecemotide (L-BLP25) along with hormonal therapy were administered for 8 weeks, followed by maintenance treatment phase starting at Week 14 (6 weeks after the last dosing of the primary treatment phase), in which subcutaneous placebo doses along with hormonal therapy were administered every 6 weeks until progressive disease (PD) was documented.

Number of Participant Utilizing Healthcare Resources

Serum Carcinoma Antigen (CA) 15-3 Levels

Single dose of sodium chloride (NaCl) 9 grams per liter (g/L) infusion as substitute for cyclophosphamide was administered intravenously, 3 days prior to the start of vaccination, followed by primary treatment phase in which weekly subcutaneous placebo doses matched to tecemotide (L-BLP25) along with hormonal therapy were administered for 8 weeks, followed by maintenance treatment phase starting at Week 14 (6 weeks after the last dosing of the primary treatment phase), in which subcutaneous placebo doses along with hormonal therapy were administered every 6 weeks until progressive disease (PD) was documented.

Overall Study

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Ifosfamide

Dacarbazine

Isophosphamide mustard

Mesna

Mechlorethamine

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Control-Arm phase III high-risk CINSARC:

Patients will be treated by doxorubicin (60 or 75mg/m² day or 20- or 25 mg/m² per day from day1 to day 3) + ifosfamide (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices of a 21-days cycle for up to 3 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).

Experimental-Arm phase III high-risk CINSARC:

Patients will be treated by doxorubicin (60 or 75mg/m² day or 20 or 25 mg/m² per day from day1 to day 3) + ifosfamide (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices of a 21-days cycle for up to 6 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).

Patients will be treated at the discretion of the investigator

A treatment cycle consists of 3 weeks. Doxorubicin will be administered from day 1 to day 3 (60 or 75mg/m² day or 20 or 25 mg/m² per day), repeated every 3 weeks, up to 3 cycles.

A treatment cycle consists of 3 weeks. Treatment may continue up to 3 cycles. Ifosfamide will be administered from day 1 to day 3 (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices, repeated every 3 weeks, up to 3 cycles.

Ifosfamide or dacarbazine

A treatment cycle consists of 3 weeks. Doxorubicin will be administered from day 1 to day 3 (60 or 75mg/m² day or 20 or 25 mg/m² per day), repeated every 3 weeks, up to 6 cycles.

A treatment cycle consists of 3 weeks. Ifosfamide will be administered from day 1 to day 3 (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices, repeated every 3 weeks, up to 6 cycles.

Drug at the discretion of the investigator.

At the discretion of the investigator

Antoine ITALIANO, MD, PhD

Simone MATHOULIN-PELISSIER, MD, PhD

Antoine ITALIANO

Nicolas ISAMBERT

Nicolas ISAMBERT, MD

Valérie LEBRUN-LY, MD

Jean-Yves BLAY, MD, PhD

François BERTUCCI, MD, PhD

Nelly FIRMIN, MD

Emmanuelle BOMPAS, MD

Jean-Emmanuel KURTZ, MD, PhD

Christine CHEVREAU

Axel LE CESNE, MD

The primary objective of this trial is to investigate whether the addition of 3 additional neo-adjuvant cycles of chemotherapy (doxorubicin based chemotherapy) to standard management according to the ISG-STS 10-01 study (3 cycles of neoadjuvant doxorubicin based chemotherapy + surgery +/- radiotherapy) improves the outcome of high-risk CINSARC patients with resectable soft-tissue sarcoma (STS). Primary endpoint is metastatic progression-free survival (M-PFS, after 3 years of follow-up).

For high-risk CINSARC patients, this is a multicenter randomized two-arm phase III trial, with a ratio 1:1:

* Arm A: standard management (3 cycles of neoadjuvant doxorubicin based chemotherapy + surgery +/- radiotherapy)
* Arm B: experimental arm (6 cycles of neoadjuvant doxorubicin based chemotherapy + surgery +/- radiotherapy)

For low-risk CINSARC patients, this a multicenter prospective cohort with treatment at the discretion of the investigator.

This is a multicenter trial with:

* An open randomized two-arm phase III trial for high-risk CINSARC patients assessing whether the addition of 3 additional neo-adjuvant cycles of chemotherapy (doxorubicin based chemotherapy) to standard management (3 cycles of neoadjuvant anthracycline based chemotherapy + surgery +/- radiotherapy) improves the outcome of patients
* a prospective cohort for low-risk CINSARC patients.

Benefit of Intensified Peri-operative Chemotherapy Within High-risk CINSARC Patients With Resectable Soft-tissue Sarcomas

Phase III Trial Investigating the Potential Benefit of Intensified Peri-operative Chemotherapy With in High-risk CINSARC Patients With Resectable Soft-tissue SARComas

Metastasis progression-free survival (M-PFS) defined as the time interval between the date of randomization and the date of death or distant progression.

Loco-regional relapse-free survival (LR-RFS) defined as the time interval between the randomization date and the date of death or loco-regional progression.

Progression-free survival (PFS) defined as the time interval between the randomization date and the date of death or progression (as per RECIST v1.1).

Overall survival (OS) defined as the time interval between the randomization date and the date of death.

Best overall response under treatment as per RECIST v1.1.

Histological response defined as the proportion of recognizable cells on the tumor sample.

Toxicity graded using the common toxicity criteria from the NCI v5.

Progression-free survival defined as the time interval between the randomization date and the date of death or progression (as per RECIST v1.1).

Metastasis progression-free survival defined as the time interval between the inclusion date and the date of death or distant progression.

Description of the treatment efficacy in terms of 3-years loco-regional progression-free survival defined as the time interval between the randomization date and the date of death or loco-regional progression.

Overall survival defined as the time interval between the inclusion date and the date of death.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
STRIDE - STimulating Immune Response In aDvanced brEast Cancer	NCT00925548	Breast Cancer	Tecemotide (L-B... Placebo of tece... cyclophosphamid... sodium chloride...	18 Years -	EMD Serono
Benefit of Intensified Peri-operative Chemotherapy Within High-risk CINSARC Patients With Resectable Soft-tissue Sarcomas	NCT03805022	Non-metastatic ... Resectable	Doxorubicin Ifosfamide or d... Doxorubicin Ifosfamide or d... At the discreti...	18 Years -	Institut Bergonié
Benefit of Intensified Peri-operative Chemotherapy Within High-risk CINSARC Patients With Resectable Soft-tissue Sarcomas	NCT03805022	Non-metastatic ... Resectable	Doxorubicin Ifosfamide or d... Doxorubicin Ifosfamide or d... At the discreti...	18 Years -	Institut Bergonié
Benefit of Intensified Peri-operative Chemotherapy Within High-risk CINSARC Patients With Resectable Soft-tissue Sarcomas	NCT03805022	Non-metastatic ... Resectable	Doxorubicin Ifosfamide or d... Doxorubicin Ifosfamide or d... At the discreti...	18 Years -	Institut Bergonié
STRIDE - STimulating Immune Response In aDvanced brEast Cancer	NCT00925548	Breast Cancer	Tecemotide (L-B... Placebo of tece... cyclophosphamid... sodium chloride...	18 Years -	EMD Serono

Spots Global Cancer Trial Database for phase iii trial