Solid TumorsPhase 1/2METROmaJXNCT02630368
A Study of Metronomic CP and JX-594 in Patients With Advanced Breast Cancer and Advanced Soft-tissue Sarcoma (METROmaJX)
A Phase 1/2 study testing Cyclophosphamide and JX-594 dose escalation, Cyclophosphamide and JX-594 and Cyclophosphamide in people with Solid Tumors and Soft-tissue Sarcoma, run by Institut Bergonié at 1 site in France.
Trial summary
Assessment of the efficacy and safety of JX-594 and metronomic cyclophosphamide in patients with advanced soft-tissue sarcoma and advanced breast cancer, once the Maximum Tolerated Dose have been determined (phase I trial). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Soft-tissue Sarcoma, Breast Cancer
- What is being tested?
- Cyclophosphamide and JX-594 dose escalation, Cyclophosphamide and JX-594 and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 197 participants
- Where
- 1 siteFrance
- Study dates
- 18 Sep 2015to Nov 2024
- 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
Main Inclusion Criteria:
- Histology:
- Phase Ib : Patient with histologically confirmed solid tumor
- Phase II :
- Patients with histologically confirmed HER2 negative breast cancer (treatment by CP+JX-594), or triple negative (treatment by avelumab + CP+JX-594)
- Patients with histologically confirmed soft tissue sarcoma confirmed by the RRePS Network, b)Progressive disease or relapse, after standard therapy according to RECIST v1.1 criteria diagnosed on the basis of two CT scan or MRI obtained at an interval less than 6 months in the period of 12 months prior to inclusion and confirmed by central review
- Metastatic or unresectable locally advanced disease
- Age ≥ 18 years
- ECOG ≤ 1 (Phase Ib), ≤ 2 (Phase II JX+CP) and ≤ 1 (Phase II avelumab+JX+CP).
- Life expectancy > 3 months,
- Measurable disease according to RECIST v1.1 outside any previously irradiated field. For patients treated by avelumab+JX+CP, at least one injectable site ≥ 2 cm and ≤ 8 cm in diameter and one distant non-injected measurable site (target site)
- At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy.
- Adequate hematological, renal, metabolic and hepatic functions.
- Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment.
- Patients informed of risks regarding drug interactions: patients receiving any substances that are inhibitors or inducers of CYP450 2B6 are ineligible
- Voluntarily signed and dated written informed consent prior to any study specific procedure.
- Patients with a social security in compliance with the French law.
Main Exclusion Criteria:
- Previous treatment with JX-594 or other vaccina vector based treatment .
- Concomitant diseases/conditions (non exhaustive list):
- Clinically significant immunodeficiency, such as HIV or active Hepatite B or C
- Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
- History of severe exfoliative skins condition requiring systemic treatment for more than 4 weeks in the last two years.
- active autoimmune disease for patients treated by avelumab
- Active central nervous system metastasis (CNS)
- Participation to a study involving a medical or therapeutic intervention in the last 30 days.
- Previous enrolment in the present study.
- Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons.
- Known hypersensitivity to any involved study drug or any of its formulation components.
- Use of steroids (any route of administration), interferon/pegylated interferon or ribavirin that cannot be discontinued within 14 days prior to any JX-594 dose.
- No prior malignancy except for the following: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage 1 or Stage 2 cancer from which the patient is currently in complete remission or any other cancer from which the patient has been disease-free for 3 years.
- Active cardiovascular disease, including but not limited to significant coronary artery disease (e.g. requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months. (treatment by CP+JX)
- Inability to suspend treatment with anti-hypertensive medication for 48 hours prior to and 48 hours after all JX-594 treatments.
- Pulse oximetry O2 saturation < 90% at rest on room air.
- Experienced a severe systemic reaction or side-effect as result of previous smallpox vaccination.
- Cardiac disease: LVEF out of normal limits ; cumulative dose of anthracyclines in excess of 450 mg/m²
- Known urinary tract obstruction
- Household contact exclusions for patients enrolled: children< 1 year old ; People with skin disease (e.g., eczema, atopic dermatitis and related diseases…), Immunocompromised hosts (severe deficiencies in cell-mediated immunity, including AIDS, organ transplant recipients, hematologic malignancies)
- Vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivated vaccines.
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Institut Bergonie
Bordeaux, 33076
Antoine ITALIANO, MD, PhD, +33 524071947, a.italiano@bordeaux.unicancer.fr
About this study
Official title: A Phase I/II Study of Metronomic Cyclophosphamide and Oncolytic Poxvirus JX-594 in Patients With Advanced Hormone-receptor Positive and Triple Negative Breast Cancer and Advanced Soft Tissue Sarcoma (METROmaJX)
Assessment of the efficacy and safety of JX-594 and metronomic cyclophosphamide in patients with advanced soft-tissue sarcoma and advanced breast cancer, once the Maximum Tolerated Dose have been determined (phase I trial).
Phase I study: this is a prospective open-labeled phase I trial based on a dose escalating study design assessing two dose levels of JX594 when prescribed in combination with metronomic cyclophosphamide.
Read more
Phase II trials with two treatments strategies:
Metronomic CP + JX-594: phase II study sarcoma: this is a monocentric, randomized two-arm non comparative phase 2 study assessing efficacy and safety of JX-594 in association with metronomic cyclophosphamide in patients with advanced soft-tissue sarcoma.
Metronomic CP + JX-594: phase II study breast cancer: this is a monocentric, single-arm phase II study, assessing efficacy and safety of JX-594 in association with metronomic cyclophosphamide in patients with advanced breast cancer.
Metronomic CP + JX-594 + Avelumab: phase II study sarcoma: this is a monocentric, single arm phase II study assessing efficacy and safety of avelumab in combination with IT JX-594 and metronomic cyclophosphamide in patients with advanced soft-tissue sarcoma.
Metronomic CP + JX-594 + Avelumab:: phase II study breast cancer: this is a monocentric, single-arm phase II study, assessing efficacy and safety of avelumab in combination with IT JX-594 and metronomic cyclophosphamide in patients with advanced breast cancer.
Read the detailed description
For the phase I study, this is a prospective open-label phase I trial based on a dose escalating study design assessing two dose level of JX-594 when associated to metronomic cyclophosphamide.
For the phase II study, two distincts treatment strategies will be evaluated.
First, treatment by JX-594 and metronomic cyclophosphamide:
- stratum soft-tissue sarcoma, this is a monocenter, randomized non comparative phase II clinical trial. This phase II trial was based on an optimal 2-stage Simon's design. Randomization 2:1 with 2 patients randomized in experimental arm n°1 (association of metronomic cyclophosphamide and JX-594) and 1 patient randomized in control arm n°2 (treatment by metronomic cyclophosphamide alone).
- stratum breast cancer, this is a monocenter, one-arm phase II clinical trial, based on two-stage optimal Simon's design (association of metronomic cyclophosphamide and JX-594).
Second, treatment by Avelumab, intratumoral JX-594 and metronomic cyclophosphamide:
- stratum soft-tissue sarcoma, this is a monocenter, single arm phase II clinical trial based on an optimal 2-stage Simon's design.
- stratum breast cancer, this is a monocenter, one-arm phase II clinical trial, based on two-stage optimal Simon's design).
- Conditions
- Solid Tumors, Soft-tissue Sarcoma, Breast Cancer
- Being tested
- Cyclophosphamide and JX-594 dose escalation, Cyclophosphamide and JX-594, Cyclophosphamide, Avelumab and JX-594 and Cyclophosphamide
- Keywords
- Advanced Soft-tissue Sarcoma, Advanced Breast Cancer, Maximum Tolerated Dose, Efficacy and safety, Immunotherapy
- Medical subject headings
- Sarcoma, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclophosphamide and JX-594 dose escalationDrug
Also called Brand name : ENDOXAN, Brand name: Pexa-Vec
Metronomic cyclophosphamide will be administered orally, 50 mg twice daily, one week on/one week off. JX-594 will be administered, as designated by assigned dose-level, intraveinously, on Days 8 and 22 of cycle 1, and on days 8 of each subsequent cycles. One cycle consits of 28 days.
Cyclophosphamide and JX-594Drug
Also called Brand name : ENDOXAN, Brand name: Pexa-Vec
Metronomic cyclophosphamide will be administered orally, 50 mg twice daily, one week on/one week off. JX-594 will be administered, as the dose recommended in the experimental phase I dose escalating study, intraveinously, on Days 8 and 22 of cycle 1, and on days 8 of each subsequent cycles. One cycle consits of 28 days.
CyclophosphamideDrug
Also called Brand name : ENDOXAN
Metronomic cyclophosphamide will be administered orally, 50 mg twice daily, one week on/one week off.
Avelumab and JX-594 and CyclophosphamideDrug
Also called Brand name: ENDOXAN, Brand name: Pexa-Vec, Brand name: Avelumab
Avelumab will be administered by intravenous infusion (10 mg/kg) every 2 weeks, starting at Day 15 of cycle 1.
Cyclophosphamide wil be administered bi-daily (50 mg x 2), starting 7 days prior to cycle 1 day 1 ("impregnation phase") and given on a week on/week off schedule.
JX-594 will be administered by intratumoral injection (1 x109 p.f.u) on day 1 of cycle 1, every 2 weeks, for a maximum of 4 injections .
| Study group | Role | What they receive |
|---|---|---|
| Experimental phase I dose escalating | Experimental | Prospective open-labeled phase I trial.
Combination of cyclophosphamide and JX-594 dose escalation. Metronomic cyclophosphamide will be administered orally, 50 mg twice daily, one week on/one week off. JX-594 will be administered, as designated by assigned dose-level, intraveinously, on Days 8 and 22 of cycle 1, and on days 8 of each subsequent cycles. One cycle consits of 28 days.
Number of subjects : 14 Receives: Drug: Cyclophosphamide and JX-594 dose escalation |
| Experimental group soft-tissue sarcoma, treatment by JX-594 + Metronomic cyclophosphamide | Experimental | Randomized non comparative phase II clinical trial : Arm 1.
Experimental phase II soft-tissue sarcoma :
Combination of cyclophosphamide and JX-594. Metronomic cyclophosphamide will be administered orally, 50 mg twice daily, one week on/one week off. JX-594 will be administered, as the dose recommended in the experimental phase I dose escalating study, intraveinously, on Days 8 and 22 of cycle 1, and on days 8 of each subsequent cycles. One cycle consits of 28 days.
Number of subjects : 48 Receives: Drug: Cyclophosphamide and JX-594 |
| Control group soft-tissue sarcoma, treatment by JX-594 + Metronomic cyclophosphamide | Experimental | Randomized non comparative phase II clinical trial : Arm 2.
Control-arm phase II soft-tissue sarcoma :
Patients will be treated by metronomic cyclophosphamide. Cyclophosphamide will be administered 50 mg twice daily orally, one week on/one week off. One cycle consits of 28 days.
Number of subjects : 24 Receives: Drug: Cyclophosphamide |
| Experimental group breast cancer, treatment by JX-594 + Metronomic cyclophosphamide | Experimental | Single-arm phase II clinical trial.
Experimental phase II Group breast cancer :
Combination of cyclophosphamide and JX-594. Metronomic cyclophosphamide will be administered orally, 50 mg twice daily, one week on/one week off. JX-594 will be administered, as the dose recommended in the experimental phase I dose escalating study, intraveinously, on Days 8 and 22 of cycle 1, and on days 8 of each subsequent cycles. One cycle consits of 28 days.
Number of subjects : 32 Receives: Drug: Cyclophosphamide and JX-594 |
| Experimental group soft-tissue sarcoma, treatment by Avelumab + ITJX-594 + Metronomic CP | Experimental | Experimental phase II soft-tissue sarcoma :
Combination of avelumab in combination with intratumoral JX-594 and metronomic cyclophosphamide.
Avelumab will be administered by intravenous infusion every 2 weeks, starting at Day 15 of cycle 1.
Cyclophosphamide wil be administered orally, 50 mg twice daily, one Week on/one Week off, starting 7 days prior to cycle 1 day 1 ("impregnation phase").
JX-594 will be administered by intratumoral injection on day 1 of cycle 1, every 2 weeks, for a maximum of 4 injections.
Number of subjects : 47 Receives: Drug: Avelumab and JX-594 and Cyclophosphamide |
| Experimental group breast cancer, treatment by Avelumab + IT JX-594 + Metronomic CP | Experimental | Experimental phase II breast cancer :
Combination of avelumab in combination with intratumoral JX-594 and metronomic cyclophosphamide.
Avelumab will be administered by intravenous infusion every 2 weeks, starting at Day 15 of cycle 1.
Cyclophosphamide wil be administered orally, 50 mg twice daily, one Week on/one Week off, starting 7 days prior to cycle 1 day 1 ("impregnation phase").
JX-594 will be administered by intratumoral injection on day 1 of cycle 1, every 2 weeks, for a maximum of 4 injections.
Number of subjects : 32 Receives: Drug: Avelumab and JX-594 and Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ib : Maximum Tolerated Dose evaluated on the first cycle (D1 to D28) of the combination of JX-594 And metronomic cyclophosphamide
the MTD is defined as the highest dose at which no more than 1 in 6 of the patients in the cohort experienced a DLT in the first treatment cycle
Measured: during the first cycle (28 days)
Phase II : Advanced soft-tissue sarcoma: Assessment of the antitumor activity of the association of JX-594 and metronomic cyclophosphamide based on 6 month non-progression (CR, PR or SD more than 24 weeks) following RECIST v1.1 criteria
Non-progression is defined as complete or partial response or stable disease, as per RECIST v1.1
Measured: Phase II : 6 months after the beginning of treatment
Phase II : Advanced Breast cancer: Assessment of the antitumor activity of the association of JX-594 and metronomic cyclophosphamide Efficacy will be defined based on objective response under treatment (CR or PR) following RECIST v1.1 criteria
Objective response is defined as complete or partial response as per RECIST v1.1
Measured: Phase II : 6 months after the beginning of treatment
Phase II : Advanced soft-tissue sarcoma: Assessment of the antitumor activity of Avelumab in combination with IT JX-594 and metronomic cyclophosphamide based on 6 month non-progression (CR, PR or SD more than 24 weeks) following RECIST v1.1 criteria
Non-progression is defined as complete or partial response or stable disease, as per RECIST v1.1
Measured: Phase II : 6 months after the beginning of treatment
Phase II : Advanced Breast cancer: Assessment of the antitumor activity of avelumab in combination with IT JX-594 and metronomic cyclophosphamide Efficacy will be defined based on objective response under treatment following RECIST v1.1 criteria
Objective response is defined as complete or partial response as per RECIST v1.1
Measured: Phase II : 6 months after the beginning of treatment
Secondary outcomes (41)
Phase Ib : Recommended Phase II dose (RP2D) of the association of JX-594 and metronomic cyclophosphamide
Data from all cycles will be used to define the dose level of JX-594 to be recommended for further investigations in phase II
Measured: Phase Ib : Throughout the 6 months of treatment period
Phase Ib: Objective response under treatment as per RECIST V1.1
Objective response is defined as complete or partial response as per RECIST v1.1
Measured: an average of 6 months
Phase Ib: Best overall response as per RECIST V1.1
- Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation (as per RECIST v1.1).
Measured: an average of 6 months
Phase Ib: 6-months non-progression as per RECIST V1.1
Non-progression is defined as complete or partial response or stable disease, as per RECIST v1.1
Measured: 6-months after the beginning of treatment
Phase Ib: 1-year progression-free survival as per RECIST V1.1
PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)
Measured: 1-year after the beginning of treatment
Phase Ib: 2-year progression-free survival as per RECIST V1.1
PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)
Measured: 2-year after the beginning of treatment
Phase Ib : Pharmacokinetics (PK): PK measurements expressed as Area Under the curve forJX-594
Measured: Day 8 of cycle 1, Day 15 of cycle 1, Day 22 of cycle 1, Day 1 of cycle 2, Day 8 of cycle 2, Day 22 of cycle 2, Day 8 of cycle 3, Day 8 of cycle 4, Day 8 of cycle 6 (Each cycle = 28 days)
Phase Ib : Pharmacokinetics (PK): PK measurements expressed as half-life forJX-594
Measured: Day 8 of cycle 1, Day 15 of cycle 1, Day 22 of cycle 1, Day 1 of cycle 2, Day 8 of cycle 2, Day 22 of cycle 2, Day 8 of cycle 3, Day 8 of cycle 4, Day 8 of cycle 6 (Each cycle = 28 days)
Phase Ib : Pharmacokinetics (PK): PK measurements expressed as Concentration peak forJX-594
Measured: Day 8 of cycle 1, Day 15 of cycle 1, Day 22 of cycle 1, Day 1 of cycle 2, Day 8 of cycle 2, Day 22 of cycle 2, Day 8 of cycle 3, Day 8 of cycle 4, Day 8 of cycle 6 (Each cycle = 28 days)
Phase Ib : Dose-Limiting toxicity of the association of JX-594 and metronomic cyclophosphamide
Measured: during the first cycle (cycle = 28 days)
Phase Ib : Predictive biomarkers analysis (cytokines levels)
Measured: baseline, day 8 of cycle 1, day 22 of cycle 1, day 8 of cycle 2, day 8 of cycle 4, day 8 of cycle 6. Each cycle = 28 days
Phase Ib : Predictive biomarkers analysis (lymphocytes levels)
Measured: baseline, day 8 of cycle 1, day 22 of cycle 1, day 8 of cycle 2, day 8 of cycle 4, day 8 of cycle 6. Each cycle = 28 days
Phase II : Best overall response defined as per RECIST v1.1 criteria
Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation (as per RECIST v1.1).
Measured: an average of 6 months
Phase II : For sarcoma only: objective response following CHOI criteria
Measured: an average of 6 months
Phase II : For sarcoma only: best overall response following CHOI criteria
Measured: an average of 6 months
Phase II : For sarcoma only: 6- month non-progression following CHOI criteria
Measured: 6-months after the beginning of treatment
Phase II : 1-year Progression-Free Survival (PFS) defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause), whichever occurs first
PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)
Measured: one year after the beginning of treatment
Phase II : 2-year Progression-Free Survival (PFS) defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause), whichever occurs first
PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)
Measured: two years the beginning of treatment
Phase II : 1-year Overall Survial (OS) defined as the time from study treatment initiation to death (of any cause)
OS defined as the time from study treatment initiation to death (of any cause)
Measured: one year after the beginning of treatment
Phase II : 2-year Overall Survial (OS) defined as the time from study treatment initiation to death (of any cause)
OS defined as the time from study treatment initiation to death (of any cause)
Measured: two year after the beginning of treatment
Phase II : Toxicity graded using the common toxicity criteria from the NCI v4.0
assessef with NCI-CTCAE V4
Measured: an average of 6 months
Predictive biomarkers (cytokines level)
Measured: baseline, day 8 of cycle 1, day 22 of cycle 1, day 8 of cycle 2, day 8 of cycle 4, day 8 of cycle 6. Each cycle = 28 days
Predictive biomarkers (lymphocytes level)
Measured: baseline, day 8 of cycle 1, day 22 of cycle 1, day 8 of cycle 2, day 8 of cycle 4, day 8 of cycle 6. Each cycle = 28 days
Phase II : Relationship between levels of anti-JX-594 antibodies and efficacy of CP + JX-594 in terms of 6-month non progression for sarcoma (as per RECIST V1.1)
Measured: Six months after the beginning of treatment
Phase II : Relationship between levels of anti-JX-594 antibodies and efficacy of CP + JX-594 in terms of objective response for breast cancer (as per RECIST V1.1)
Measured: an average of 6 months
Phase II : Relationship between activation of the pRB/E2F/TK pathway and efficacy of CP + JX-594 on available archived tumor tissue in terms of 6- month non progression for sarcoma (as per RECIST V1.1)
Measured: Phase II : Six months after the beginning of treatment
Phase II : Relationship between activation of the pRB/E2F/TK pathway and efficacy of CP + JX-594 on available archived tumor tissue in terms objective response for breast cancer (as per RECIST V1.1)
Measured: an average of 6 months
Phase II Soft-tissue sarcoma: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of best overall response
- Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation (as per RECIST v1.1)
Measured: an average of 6 months
Phase II Breast cancer: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of best overall response
- Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation (as per RECIST v1.1)
Measured: an average of 6 months
Phase II Breast cancer: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of 6-month non-progression
Non-progression is defined as complete or partial response or stable disease, as per RECIST v1.1
Measured: 6 months
Phase II Soft-tissue sarcoma: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of objective response Under treatment
Objective response is defined as complete or partial response as per RECIST v1.1
Measured: an average of 6 months
Phase II Soft-tissue sarcoma: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of 1-year progression-free survival
PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)
Measured: 1 year
Phase II Breast cancer: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of 1-year progression-free survival
PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)
Measured: 1 year
Phase II Soft-tissue sarcoma: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of 2-year progression-free survival
PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)
Measured: 2 years
Phase II Breast cancer: antitumor activity of avelumab in combination with IT JX-594 and metronomic CP in terms of 2-year progression-free survival
PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)
Measured: 2 years
Phase II Soft-tissue sarcoma: antitumor activity of avelumab in combination with IT JX-594 and metronomic CP in terms of 1-year overall survival
OS defined as the time from study treatment initiation to death (of any cause)
Measured: 1 year
Phase II Breast cancer: antitumor activity of avelumab in combination with IT JX-594 and metronomic CP in terms of 1-year overall survival
OS defined as the time from study treatment initiation to death (of any cause)
Measured: 1 year
Phase II Soft-tissue sarcoma: antitumor activity of avelumab in combination with IT JX-594 and metronomic CP in terms of 2-year overall survival
OS defined as the time from study treatment initiation to death (of any cause)
Measured: 2 year
Phase II Breast cancer: antitumor activity of avelumab in combination with IT JX-594 and metronomic CP in terms of 2-year overall survival
OS defined as the time from study treatment initiation to death (of any cause)
Measured: 2 year
Phase II Soft-tissue sarcoma: safety profile of avelumab in combination with IT JX-594 and metronomic CP
Safety profile will be assessed as per NCI-CTCAE v5
Measured: throughout the treatment period, an expected average of 6 months
Phase II breast cancer: safety profile of avelumab in combination with IT JX-594 and metronomic CP
Safety profile will be assessed as per NCI-CTCAE v5
Measured: throughout the treatment period, an expected average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2015 (estimated)
- Study start18 Sep 2015
- Primary completionMay 2023 (estimated)
- Study completionNov 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 197 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut Bergonié
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute, France, Fondation ARC, Merck Sharp & Dohme LLC, Transgene
- Responsible party
- Sponsor
- Investigators
- Antoine ITALIANO, MD, PhD, Study chair, Institut Bergonié
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02630368
- Sponsor's protocol ID
- IB 2014-02
- Other IDs
- 2014-001078-33, 2014
- Acronym
- METROmaJX
- Status last verified
- Jan 2022
- First submitted
- 19 Nov 2015
- Last updated
- 2 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Metronomic Cyclophosphamide and Oncolytic Poxvirus JX-594 in Patients With Advanced Hormone-receptor Positive and Triple Negative Breast Cancer and Advanced Soft Tissue Sarcoma (METROmaJX)
- ClinicalTrials.gov ID
- NCT02630368
- Acronym / sponsor ID
- METROmaJX / IB 2014-02
- Conditions
- Solid Tumors, Soft-tissue Sarcoma, Breast Cancer
- Keywords
- Advanced Soft-tissue Sarcoma, Advanced Breast Cancer, Maximum Tolerated Dose, Efficacy and safety, Immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 197 participants (estimated)
- Lead sponsor
- Institut BergoniéUniversity, hospital or other
- Collaborators
- National Cancer Institute, France, Fondation ARC, Merck Sharp & Dohme LLC, Transgene
- Study start
- 18 Sep 2015 (actual)
- Primary completion
- May 2023 (estimated)
- Study completion
- Nov 2024 (estimated)
- First posted
- 15 Dec 2015 (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.
Assessment of the efficacy and safety of JX-594 and metronomic cyclophosphamide in patients with advanced soft-tissue sarcoma and advanced breast cancer, once the Maximum Tolerated Dose have been determined (phase I trial).
Phase I study: this is a prospective open-labeled phase I trial based on a dose escalating study design assessing two dose levels of JX594 when prescribed in combination with metronomic cyclophosphamide.
Phase II trials with two treatments strategies:
Metronomic CP + JX-594: phase II study sarcoma: this is a monocentric, randomized two-arm non comparative phase 2 study assessing efficacy and safety of JX-594 in association with metronomic cyclophosphamide in patients with advanced soft-tissue sarcoma.
Metronomic CP + JX-594: phase II study breast cancer: this is a monocentric, single-arm phase II study, assessing efficacy and safety of JX-594 in association with metronomic cyclophosphamide in patients with advanced breast cancer.
Metronomic CP + JX-594 + Avelumab: phase II study sarcoma: this is a monocentric, single arm phase II study assessing efficacy and safety of avelumab in combination with IT JX-594 and metronomic cyclophosphamide in patients with advanced soft-tissue sarcoma.
Metronomic CP + JX-594 + Avelumab:: phase II study breast cancer: this is a monocentric, single-arm phase II study, assessing efficacy and safety of avelumab in combination with IT JX-594 and metronomic cyclophosphamide in patients with advanced breast cancer.
Detailed description
For the phase I study, this is a prospective open-label phase I trial based on a dose escalating study design assessing two dose level of JX-594 when associated to metronomic cyclophosphamide.
For the phase II study, two distincts treatment strategies will be evaluated.
First, treatment by JX-594 and metronomic cyclophosphamide:
- stratum soft-tissue sarcoma, this is a monocenter, randomized non comparative phase II clinical trial. This phase II trial was based on an optimal 2-stage Simon's design. Randomization 2:1 with 2 patients randomized in experimental arm n°1 (association of metronomic cyclophosphamide and JX-594) and 1 patient randomized in control arm n°2 (treatment by metronomic cyclophosphamide alone).
- stratum breast cancer, this is a monocenter, one-arm phase II clinical trial, based on two-stage optimal Simon's design (association of metronomic cyclophosphamide and JX-594).
Second, treatment by Avelumab, intratumoral JX-594 and metronomic cyclophosphamide:
- stratum soft-tissue sarcoma, this is a monocenter, single arm phase II clinical trial based on an optimal 2-stage Simon's design.
- stratum breast cancer, this is a monocenter, one-arm phase II clinical trial, based on two-stage optimal Simon's design).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Experimental phase I dose escalating | Experimental | Drug: Cyclophosphamide and JX-594 dose escalationProspective open-labeled phase I trial. Combination of cyclophosphamide and JX-594 dose escalation. Metronomic cyclophosphamide will be administered orally, 50 mg twice daily, one week on/one week off. JX-594 will be administered, as designated by assigned dose-level, intraveinously, on Days 8 and 22 of cycle 1, and on days 8 of each subsequent cycles. One cycle consits of 28 days. Number of subjects : 14 |
| Experimental group soft-tissue sarcoma, treatment by JX-594 + Metronomic cyclophosphamide | Experimental | Drug: Cyclophosphamide and JX-594Randomized non comparative phase II clinical trial : Arm 1. Experimental phase II soft-tissue sarcoma : Combination of cyclophosphamide and JX-594. Metronomic cyclophosphamide will be administered orally, 50 mg twice daily, one week on/one week off. JX-594 will be administered, as the dose recommended in the experimental phase I dose escalating study, intraveinously, on Days 8 and 22 of cycle 1, and on days 8 of each subsequent cycles. One cycle consits of 28 days. Number of subjects : 48 |
| Control group soft-tissue sarcoma, treatment by JX-594 + Metronomic cyclophosphamide | Experimental | Drug: CyclophosphamideRandomized non comparative phase II clinical trial : Arm 2. Control-arm phase II soft-tissue sarcoma : Patients will be treated by metronomic cyclophosphamide. Cyclophosphamide will be administered 50 mg twice daily orally, one week on/one week off. One cycle consits of 28 days. Number of subjects : 24 |
| Experimental group breast cancer, treatment by JX-594 + Metronomic cyclophosphamide | Experimental | Drug: Cyclophosphamide and JX-594Single-arm phase II clinical trial. Experimental phase II Group breast cancer : Combination of cyclophosphamide and JX-594. Metronomic cyclophosphamide will be administered orally, 50 mg twice daily, one week on/one week off. JX-594 will be administered, as the dose recommended in the experimental phase I dose escalating study, intraveinously, on Days 8 and 22 of cycle 1, and on days 8 of each subsequent cycles. One cycle consits of 28 days. Number of subjects : 32 |
| Experimental group soft-tissue sarcoma, treatment by Avelumab + ITJX-594 + Metronomic CP | Experimental | Drug: Avelumab and JX-594 and CyclophosphamideExperimental phase II soft-tissue sarcoma : Combination of avelumab in combination with intratumoral JX-594 and metronomic cyclophosphamide. Avelumab will be administered by intravenous infusion every 2 weeks, starting at Day 15 of cycle 1. Cyclophosphamide wil be administered orally, 50 mg twice daily, one Week on/one Week off, starting 7 days prior to cycle 1 day 1 ("impregnation phase"). JX-594 will be administered by intratumoral injection on day 1 of cycle 1, every 2 weeks, for a maximum of 4 injections. Number of subjects : 47 |
| Experimental group breast cancer, treatment by Avelumab + IT JX-594 + Metronomic CP | Experimental | Drug: Avelumab and JX-594 and CyclophosphamideExperimental phase II breast cancer : Combination of avelumab in combination with intratumoral JX-594 and metronomic cyclophosphamide. Avelumab will be administered by intravenous infusion every 2 weeks, starting at Day 15 of cycle 1. Cyclophosphamide wil be administered orally, 50 mg twice daily, one Week on/one Week off, starting 7 days prior to cycle 1 day 1 ("impregnation phase"). JX-594 will be administered by intratumoral injection on day 1 of cycle 1, every 2 weeks, for a maximum of 4 injections. Number of subjects : 32 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Cyclophosphamide and JX-594 dose escalationAlso: Brand name : ENDOXAN, Brand name: Pexa-VecMetronomic cyclophosphamide will be administered orally, 50 mg twice daily, one week on/one week off. JX-594 will be administered, as designated by assigned dose-level, intraveinously, on Days 8 and 22 of cycle 1, and on days 8 of each subsequent cycles. One cycle consits of 28 days. | Drug | Experimental phase I dose escalating |
| Cyclophosphamide and JX-594Also: Brand name : ENDOXAN, Brand name: Pexa-VecMetronomic cyclophosphamide will be administered orally, 50 mg twice daily, one week on/one week off. JX-594 will be administered, as the dose recommended in the experimental phase I dose escalating study, intraveinously, on Days 8 and 22 of cycle 1, and on days 8 of each subsequent cycles. One cycle consits of 28 days. | Drug | Experimental group breast cancer, treatment by JX-594 + Metronomic cyclophosphamide, Experimental group soft-tissue sarcoma, treatment by JX-594 + Metronomic cyclophosphamide |
| CyclophosphamideAlso: Brand name : ENDOXANMetronomic cyclophosphamide will be administered orally, 50 mg twice daily, one week on/one week off. | Drug | Control group soft-tissue sarcoma, treatment by JX-594 + Metronomic cyclophosphamide |
| Avelumab and JX-594 and CyclophosphamideAlso: Brand name: ENDOXAN, Brand name: Pexa-Vec, Brand name: AvelumabAvelumab will be administered by intravenous infusion (10 mg/kg) every 2 weeks, starting at Day 15 of cycle 1. Cyclophosphamide wil be administered bi-daily (50 mg x 2), starting 7 days prior to cycle 1 day 1 ("impregnation phase") and given on a week on/week off schedule. JX-594 will be administered by intratumoral injection (1 x109 p.f.u) on day 1 of cycle 1, every 2 weeks, for a maximum of 4 injections . | Drug | Experimental group breast cancer, treatment by Avelumab + IT JX-594 + Metronomic CP, Experimental group soft-tissue sarcoma, treatment by Avelumab + ITJX-594 + Metronomic CP |
Primary outcome
Phase Ib : Maximum Tolerated Dose evaluated on the first cycle (D1 to D28) of the combination of JX-594 And metronomic cyclophosphamide
Time frame: during the first cycle (28 days)
the MTD is defined as the highest dose at which no more than 1 in 6 of the patients in the cohort experienced a DLT in the first treatment cycle
Phase II : Advanced soft-tissue sarcoma: Assessment of the antitumor activity of the association of JX-594 and metronomic cyclophosphamide based on 6 month non-progression (CR, PR or SD more than 24 weeks) following RECIST v1.1 criteria
Time frame: Phase II : 6 months after the beginning of treatment
Non-progression is defined as complete or partial response or stable disease, as per RECIST v1.1
Phase II : Advanced Breast cancer: Assessment of the antitumor activity of the association of JX-594 and metronomic cyclophosphamide Efficacy will be defined based on objective response under treatment (CR or PR) following RECIST v1.1 criteria
Time frame: Phase II : 6 months after the beginning of treatment
Objective response is defined as complete or partial response as per RECIST v1.1
Phase II : Advanced soft-tissue sarcoma: Assessment of the antitumor activity of Avelumab in combination with IT JX-594 and metronomic cyclophosphamide based on 6 month non-progression (CR, PR or SD more than 24 weeks) following RECIST v1.1 criteria
Time frame: Phase II : 6 months after the beginning of treatment
Non-progression is defined as complete or partial response or stable disease, as per RECIST v1.1
Phase II : Advanced Breast cancer: Assessment of the antitumor activity of avelumab in combination with IT JX-594 and metronomic cyclophosphamide Efficacy will be defined based on objective response under treatment following RECIST v1.1 criteria
Time frame: Phase II : 6 months after the beginning of treatment
Objective response is defined as complete or partial response as per RECIST v1.1
41 secondary outcomes
Phase Ib : Recommended Phase II dose (RP2D) of the association of JX-594 and metronomic cyclophosphamide
Time frame: Phase Ib : Throughout the 6 months of treatment period
Phase Ib: Objective response under treatment as per RECIST V1.1
Time frame: an average of 6 months
Phase Ib: Best overall response as per RECIST V1.1
Time frame: an average of 6 months
Phase Ib: 6-months non-progression as per RECIST V1.1
Time frame: 6-months after the beginning of treatment
Phase Ib: 1-year progression-free survival as per RECIST V1.1
Time frame: 1-year after the beginning of treatment
Phase Ib: 2-year progression-free survival as per RECIST V1.1
Time frame: 2-year after the beginning of treatment
Phase Ib : Pharmacokinetics (PK): PK measurements expressed as Area Under the curve forJX-594
Time frame: Day 8 of cycle 1, Day 15 of cycle 1, Day 22 of cycle 1, Day 1 of cycle 2, Day 8 of cycle 2, Day 22 of cycle 2, Day 8 of cycle 3, Day 8 of cycle 4, Day 8 of cycle 6 (Each cycle = 28 days)
Phase Ib : Pharmacokinetics (PK): PK measurements expressed as half-life forJX-594
Time frame: Day 8 of cycle 1, Day 15 of cycle 1, Day 22 of cycle 1, Day 1 of cycle 2, Day 8 of cycle 2, Day 22 of cycle 2, Day 8 of cycle 3, Day 8 of cycle 4, Day 8 of cycle 6 (Each cycle = 28 days)
Phase Ib : Pharmacokinetics (PK): PK measurements expressed as Concentration peak forJX-594
Time frame: Day 8 of cycle 1, Day 15 of cycle 1, Day 22 of cycle 1, Day 1 of cycle 2, Day 8 of cycle 2, Day 22 of cycle 2, Day 8 of cycle 3, Day 8 of cycle 4, Day 8 of cycle 6 (Each cycle = 28 days)
Phase Ib : Dose-Limiting toxicity of the association of JX-594 and metronomic cyclophosphamide
Time frame: during the first cycle (cycle = 28 days)
Phase Ib : Predictive biomarkers analysis (cytokines levels)
Time frame: baseline, day 8 of cycle 1, day 22 of cycle 1, day 8 of cycle 2, day 8 of cycle 4, day 8 of cycle 6. Each cycle = 28 days
Phase Ib : Predictive biomarkers analysis (lymphocytes levels)
Time frame: baseline, day 8 of cycle 1, day 22 of cycle 1, day 8 of cycle 2, day 8 of cycle 4, day 8 of cycle 6. Each cycle = 28 days
Phase II : Best overall response defined as per RECIST v1.1 criteria
Time frame: an average of 6 months
Phase II : For sarcoma only: objective response following CHOI criteria
Time frame: an average of 6 months
Phase II : For sarcoma only: best overall response following CHOI criteria
Time frame: an average of 6 months
Phase II : For sarcoma only: 6- month non-progression following CHOI criteria
Time frame: 6-months after the beginning of treatment
Phase II : 1-year Progression-Free Survival (PFS) defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause), whichever occurs first
Time frame: one year after the beginning of treatment
Phase II : 2-year Progression-Free Survival (PFS) defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause), whichever occurs first
Time frame: two years the beginning of treatment
Phase II : 1-year Overall Survial (OS) defined as the time from study treatment initiation to death (of any cause)
Time frame: one year after the beginning of treatment
Phase II : 2-year Overall Survial (OS) defined as the time from study treatment initiation to death (of any cause)
Time frame: two year after the beginning of treatment
Phase II : Toxicity graded using the common toxicity criteria from the NCI v4.0
Time frame: an average of 6 months
Predictive biomarkers (cytokines level)
Time frame: baseline, day 8 of cycle 1, day 22 of cycle 1, day 8 of cycle 2, day 8 of cycle 4, day 8 of cycle 6. Each cycle = 28 days
Predictive biomarkers (lymphocytes level)
Time frame: baseline, day 8 of cycle 1, day 22 of cycle 1, day 8 of cycle 2, day 8 of cycle 4, day 8 of cycle 6. Each cycle = 28 days
Phase II : Relationship between levels of anti-JX-594 antibodies and efficacy of CP + JX-594 in terms of 6-month non progression for sarcoma (as per RECIST V1.1)
Time frame: Six months after the beginning of treatment
Phase II : Relationship between levels of anti-JX-594 antibodies and efficacy of CP + JX-594 in terms of objective response for breast cancer (as per RECIST V1.1)
Time frame: an average of 6 months
Phase II : Relationship between activation of the pRB/E2F/TK pathway and efficacy of CP + JX-594 on available archived tumor tissue in terms of 6- month non progression for sarcoma (as per RECIST V1.1)
Time frame: Phase II : Six months after the beginning of treatment
Phase II : Relationship between activation of the pRB/E2F/TK pathway and efficacy of CP + JX-594 on available archived tumor tissue in terms objective response for breast cancer (as per RECIST V1.1)
Time frame: an average of 6 months
Phase II Soft-tissue sarcoma: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of best overall response
Time frame: an average of 6 months
Phase II Breast cancer: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of best overall response
Time frame: an average of 6 months
Phase II Breast cancer: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of 6-month non-progression
Time frame: 6 months
Phase II Soft-tissue sarcoma: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of objective response Under treatment
Time frame: an average of 6 months
Phase II Soft-tissue sarcoma: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of 1-year progression-free survival
Time frame: 1 year
Phase II Breast cancer: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of 1-year progression-free survival
Time frame: 1 year
Phase II Soft-tissue sarcoma: antitumor actiivty of avelumab in combination with IT JX-594 and metronomic CP in terms of 2-year progression-free survival
Time frame: 2 years
Phase II Breast cancer: antitumor activity of avelumab in combination with IT JX-594 and metronomic CP in terms of 2-year progression-free survival
Time frame: 2 years
Phase II Soft-tissue sarcoma: antitumor activity of avelumab in combination with IT JX-594 and metronomic CP in terms of 1-year overall survival
Time frame: 1 year
Phase II Breast cancer: antitumor activity of avelumab in combination with IT JX-594 and metronomic CP in terms of 1-year overall survival
Time frame: 1 year
Phase II Soft-tissue sarcoma: antitumor activity of avelumab in combination with IT JX-594 and metronomic CP in terms of 2-year overall survival
Time frame: 2 year
Phase II Breast cancer: antitumor activity of avelumab in combination with IT JX-594 and metronomic CP in terms of 2-year overall survival
Time frame: 2 year
Phase II Soft-tissue sarcoma: safety profile of avelumab in combination with IT JX-594 and metronomic CP
Time frame: throughout the treatment period, an expected average of 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2022.
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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.
Antoine ITALIANO, MD, PhD study chair
Institut Bergonié
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cyclophosphamide and JX-594 dose escalation, Cyclophosphamide and JX-594 and Cyclophosphamide in people with Solid Tumors and Soft-tissue Sarcoma, run by Institut Bergonié at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: status not confirmed, as of the sponsor's last update on 2 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Antoine ITALIANO, MD, PhD (+33 524071947, a.italiano@bordeaux.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib : Maximum Tolerated Dose evaluated on the first cycle (D1 to D28) of the combination of JX-594 And metronomic cyclophosphamide (time frame: during the first cycle (28 days)). The study lists 5 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 2 Feb 2022.