Evaluation of Pembrolizumab in Lymphopenic Metastatic Breast Cancer Patients Treated With Metronomic Cyclophosphamide (CHEMOIMMUNE)
|ClinicalTrials.gov Identifier: NCT03139851|
Recruitment Status : Active, not recruiting
First Posted : May 4, 2017
Last Update Posted : June 18, 2019
The investigators hypothesize that the administration of pembrolizumab combined to metronomic cyclophosphamide may be an interesting therapeutic option for female patients breast cancer with lymphopenia.
Include only patients with breast cancer with lymphopenia is based on the particularly poor prognosis of these patients. The approach suggested here is to deplete and active the immune response of these immunosuppressed patients. The combination of pembrolizumab and cyclophosphamide would provide a higher gain in anti-tumor response in these patients than in those without lymphopenia and in chemotherapy alone.
The investigators proposal is to conduct a multicentric, non-comparative, single arm, two-stage, Phase II trial in lymphopenic patients with metastatic breast cancer.
The study is divided in 2 parts:
- a safety run-in Phase aiming to evaluate the safety of the combination therapy pembrolizumab + metronomic cyclophosphamide based on the occurrence of severe toxicities.
- a two-stage Phase II aiming to evaluate the clinical activity of the combination therapy pembrolizumab + metronomic cyclophosphamide.
In both parts of the study, patients will receive cyclophosphamide (50 mg/day, daily, per os) and pembrolizumab (200 mg every 3 weeks, intravenously [IV]). The adverse events of the two drugs are well known.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Breast Cancer||Drug: Cyclophosphamide 50mg Drug: Pembrolizumab 100 MG in 4 ML Injection||Phase 2|
The initiation of different stage of the study depend on the occurrences of severe toxicities in safety run-in phase and Clinical Benefit rate after 24 weeks in the two-stage Phase II of the study.
Both study drugs will continue to be administered as long as patient experience clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||CHEMOIMMUNE - A Phase II Study Evaluating an Anti-PD1 Monoclonal Antibody (Pembrolizumab) in Lymphopenic Metastatic Breast Cancer Patients Treated With Metronomic Cyclophosphamide|
|Actual Study Start Date :||June 27, 2017|
|Estimated Primary Completion Date :||February 2020|
|Estimated Study Completion Date :||February 2020|
Cyclophosphamide and Pembrolizumab
The treatments received are:
Drug: Cyclophosphamide 50mg
One tablet per day. Cyclophosphamide will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.
Drug: Pembrolizumab 100 MG in 4 ML Injection
IV infusion every 3 weeks. Pembrolizumab will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.
Other Name: Keytruda
- Severe Toxicities (ST) in Run-In Phase Part [ Time Frame: First 6 weeks of treatment ]
Number of severe toxicities occurring during the first 6 weeks of treatment and defined as following events evaluated as related to study drugs, using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4.03:
- any Grade ≥ 3 non hematological toxicity including in particular events of special interest
- any Grade ≥4 hematological and non-hematological Adverse Event (AE) including.
- 24-week Clinical Benefit Rate (CBR24w) in Phase II part [ Time Frame: 24 weeks of treatment ]CBR24w, defined as the percentage of Complete Response (CR), (Partial Response) PR or prolonged Stable Disease (SD) i.e. SD lasting ≥ 24 weeks (pSD) within the evaluable population of patient. Response will be evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 and the CBR24w will be summarized by a proportion together with its 95% confidence interval.
- ECI (Events of Clinical Interest) [ Time Frame: From 7 weeks to 15 months of treatment ]All AE meeting the ST definition but occurring after the first 6 weeks of treatment will be considered as an ECI.
- Overall response Rate (ORR) at 24 weeks [ Time Frame: 24 weeks of treatment ]The objective response rate (ORR) will be defined as the proportion of patients (described on the efficacy-evaluable population) who achieve complete response (CR) or partial response (PR) as best overall response at 24 weeks of treatment. ORR is based on tumor assessments (measurements according to RECIST 1.1 and irRC criteria).
- Duration of response (DoR) [ Time Frame: 15 months ]Calculated from date of first documented objective response (i.e., CR or PR) until date of first documented progression disease (measurements according to RECIST 1.1 and irRC criteria).
- Progression-Free Survival (PFS) [ Time Frame: 15 months ]Measured from the date of study drugs start to the date of the first objective radiological disease progression using RECIST 1.1 or death.
- Overall Survival (OS) [ Time Frame: 15 months ]Defined as the duration of time from start of treatment to time of death.
- Adverse events reporting [ Time Frame: 15 months ]Adverse Events (AE), vital signs, ECG, physical examination, laboratory safety assessments (hematological and biochemical parameters).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03139851
|ICO - Paul Papin|
|Angers, France, 49055|
|Centre Léon Bérard|
|Lyon, France, 69003|
|Hôpital Privé Jean Mermoz|
|Lyon, France, 69008|
|ICO - René Gauducheau|
|Saint-Herblain, France, 44805|
|Institut de cancérologie Lucien Neuwirth|
|Saint-Priest-en-Jarez, France, 42270|
|Principal Investigator:||Olivier TREDAN, MD||Centre Leon Berard|