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A Study of Metronomic CP and JX-594 in Patients With Advanced Breast Cancer and Advanced Soft-tissue Sarcoma (METROmaJX) (METROmaJX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02630368
Recruitment Status : Recruiting
First Posted : December 15, 2015
Last Update Posted : October 23, 2020
Sponsor:
Collaborators:
National Cancer Institute, France
Fondation ARC
Merck Sharp & Dohme Corp.
Transgene
Information provided by (Responsible Party):
Institut Bergonié

Brief 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).

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.


Condition or disease Intervention/treatment Phase
Solid Tumors Soft-tissue Sarcoma Breast Cancer Drug: Cyclophosphamide and JX-594 dose escalation Drug: Cyclophosphamide and JX-594 Drug: Cyclophosphamide Drug: Avelumab and JX-594 and Cyclophosphamide Phase 1 Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 197 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 18, 2015
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : November 2024


Arm Intervention/treatment
Experimental: Experimental phase I dose escalating

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

Drug: 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.
Other Names:
  • Brand name : ENDOXAN
  • Brand name: Pexa-Vec

Experimental: Experimental group soft-tissue sarcoma, treatment by JX-594 + Metronomic cyclophosphamide

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

Drug: 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.
Other Names:
  • Brand name : ENDOXAN
  • Brand name: Pexa-Vec

Experimental: Control group soft-tissue sarcoma, treatment by JX-594 + Metronomic cyclophosphamide

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

Drug: Cyclophosphamide
Metronomic cyclophosphamide will be administered orally, 50 mg twice daily, one week on/one week off.
Other Name: Brand name : ENDOXAN

Experimental: Experimental group breast cancer, treatment by JX-594 + Metronomic cyclophosphamide

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

Drug: 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.
Other Names:
  • Brand name : ENDOXAN
  • Brand name: Pexa-Vec

Experimental: Experimental group soft-tissue sarcoma, treatment by Avelumab + ITJX-594 + Metronomic CP

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

Drug: Avelumab and JX-594 and Cyclophosphamide

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 .

Other Names:
  • Brand name: ENDOXAN
  • Brand name: Pexa-Vec
  • Brand name: Avelumab

Experimental: Experimental group breast cancer, treatment by Avelumab + IT JX-594 + Metronomic CP

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

Drug: Avelumab and JX-594 and Cyclophosphamide

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 .

Other Names:
  • Brand name: ENDOXAN
  • Brand name: Pexa-Vec
  • Brand name: Avelumab




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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


Secondary Outcome Measures :
  1. 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 ]
    Data from all cycles will be used to define the dose level of JX-594 to be recommended for further investigations in phase II

  2. Phase Ib: Objective response under treatment as per RECIST V1.1 [ Time Frame: an average of 6 months ]
    Objective response is defined as complete or partial response as per RECIST v1.1

  3. Phase Ib: Best overall response as per RECIST V1.1 [ Time Frame: an average of 6 months ]
    - 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).

  4. Phase Ib: 6-months non-progression as per RECIST V1.1 [ Time Frame: 6-months after the beginning of treatment ]
    Non-progression is defined as complete or partial response or stable disease, as per RECIST v1.1

  5. Phase Ib: 1-year progression-free survival as per RECIST V1.1 [ Time Frame: 1-year after the beginning of treatment ]
    PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)

  6. Phase Ib: 2-year progression-free survival as per RECIST V1.1 [ Time Frame: 2-year after the beginning of treatment ]
    PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)

  7. 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) ]
  8. 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) ]
  9. 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) ]
  10. Phase Ib : Dose-Limiting toxicity of the association of JX-594 and metronomic cyclophosphamide [ Time Frame: during the first cycle (cycle = 28 days) ]
  11. 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 ]
  12. 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 ]
  13. Phase II : Best overall response defined as per RECIST v1.1 criteria [ Time Frame: an average of 6 months ]
    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).

  14. Phase II : For sarcoma only: objective response following CHOI criteria [ Time Frame: an average of 6 months ]
  15. Phase II : For sarcoma only: best overall response following CHOI criteria [ Time Frame: an average of 6 months ]
  16. Phase II : For sarcoma only: 6- month non-progression following CHOI criteria [ Time Frame: 6-months after the beginning of treatment ]
  17. 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 ]
    PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)

  18. 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 ]
    PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)

  19. 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 ]
    OS defined as the time from study treatment initiation to death (of any cause)

  20. 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 ]
    OS defined as the time from study treatment initiation to death (of any cause)

  21. Phase II : Toxicity graded using the common toxicity criteria from the NCI v4.0 [ Time Frame: an average of 6 months ]
    assessef with NCI-CTCAE V4

  22. 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 ]
  23. 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 ]
  24. 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 ]
  25. 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 ]
  26. 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 ]
  27. 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 ]
  28. 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 ]
    - 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)

  29. 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 ]
    - 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)

  30. 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 ]
    Non-progression is defined as complete or partial response or stable disease, as per RECIST v1.1

  31. 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 ]
    Objective response is defined as complete or partial response as per RECIST v1.1

  32. 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 ]
    PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)

  33. 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 ]
    PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)

  34. 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 ]
    PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)

  35. 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 ]
    PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)

  36. 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 ]
    OS defined as the time from study treatment initiation to death (of any cause)

  37. 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 ]
    OS defined as the time from study treatment initiation to death (of any cause)

  38. 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 ]
    OS defined as the time from study treatment initiation to death (of any cause)

  39. 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 ]
    OS defined as the time from study treatment initiation to death (of any cause)

  40. 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 ]
    Safety profile will be assessed as per NCI-CTCAE v5

  41. Phase II breast cancer: 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 ]
    Safety profile will be assessed as per NCI-CTCAE v5



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  1. 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
  2. Metastatic or unresectable locally advanced disease
  3. Age ≥ 18 years
  4. ECOG ≤ 1 (Phase Ib), ≤ 2 (Phase II JX+CP) and ≤ 1 (Phase II avelumab+JX+CP).
  5. Life expectancy > 3 months,
  6. 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)
  7. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy.
  8. Adequate hematological, renal, metabolic and hepatic functions.
  9. 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.
  10. Patients informed of risks regarding drug interactions: patients receiving any substances that are inhibitors or inducers of CYP450 2B6 are ineligible
  11. Voluntarily signed and dated written informed consent prior to any study specific procedure.
  12. Patients with a social security in compliance with the French law.

Main Exclusion Criteria:

  1. Previous treatment with JX-594 or other vaccina vector based treatment or with PD1/PDL1 antagonist for treatment by avelumab.
  2. Concomitant diseases/conditions (non exhaustive list):

    1. Clinically significant immunodeficiency, such as HIV or active Hepatite B or C
    2. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
    3. History of severe exfoliative skins condition requiring systemic treatment for more than 4 weeks in the last two years.
    4. active autoimmune disease for patients treated by avelumab
  3. Active central nervous system metastasis (CNS)
  4. Participation to a study involving a medical or therapeutic intervention in the last 30 days.
  5. Previous enrolment in the present study.
  6. Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons.
  7. Known hypersensitivity to any involved study drug or any of its formulation components.
  8. 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.
  9. 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.
  10. 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)
  11. Inability to suspend treatment with anti-hypertensive medication for 48 hours prior to and 48 hours after all JX-594 treatments.
  12. Pulse oximetry O2 saturation < 90% at rest on room air.
  13. Experienced a severe systemic reaction or side-effect as result of previous smallpox vaccination.
  14. Cardiac disease: LVEF out of normal limits ; cumulative dose of anthracyclines in excess of 450 mg/m²
  15. Known urinary tract obstruction
  16. 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)
  17. Vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivated vaccines.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02630368


Contacts
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Contact: Antoine ITALIANO, MD, PhD +33 524071947 a.italiano@bordeaux.unicancer.fr

Locations
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France
Institut Bergonie Recruiting
Bordeaux, France, 33076
Contact: Antoine ITALIANO, MD, PhD    +33 524071947    a.italiano@bordeaux.unicancer.fr   
Sponsors and Collaborators
Institut Bergonié
National Cancer Institute, France
Fondation ARC
Merck Sharp & Dohme Corp.
Transgene
Investigators
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Study Chair: Antoine ITALIANO, MD, PhD Institut Bergonié
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Responsible Party: Institut Bergonié
ClinicalTrials.gov Identifier: NCT02630368    
Other Study ID Numbers: IB 2014-02
2014-001078-33 ( EudraCT Number )
First Posted: December 15, 2015    Key Record Dates
Last Update Posted: October 23, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institut Bergonié:
Advanced Soft-tissue Sarcoma
Advanced Breast Cancer
Maximum Tolerated Dose
Efficacy and safety
Immunotherapy
Additional relevant MeSH terms:
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Breast Neoplasms
Sarcoma
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists