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Neoadjuvant Chemotherapy and Retifanlimab in Patients With Selected Retroperitoneal Sarcomas (TORNADO) (TORNADO)

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ClinicalTrials.gov Identifier: NCT04968106
Recruitment Status : Not yet recruiting
First Posted : July 20, 2021
Last Update Posted : December 7, 2021
Sponsor:
Collaborator:
Incyte Biosciences International Sàrl
Information provided by (Responsible Party):
Institut Bergonié

Tracking Information
First Submitted Date  ICMJE July 13, 2021
First Posted Date  ICMJE July 20, 2021
Last Update Posted Date December 7, 2021
Estimated Study Start Date  ICMJE February 1, 2022
Estimated Primary Completion Date March 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 13, 2021)
Assessment of the antitumor activity of retifanlimab when prescribed in association with neoadjuvant chemotherapy (doxorubicin+ifosfamide) [ Time Frame: 5 months after treatment onset ]
Antitumor activity will be assessed in terms of histological response based on surgical sample
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2021)
  • 1-year progression-free survival [ Time Frame: 1 year ]
    Progression-free survival (PFS) is defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)
  • 3-year progression-free survival [ Time Frame: 3 years ]
    Progression-free survival (PFS) is defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause)
  • 1-year overall survival [ Time Frame: 1 year ]
    Overall Survival (OS) is defined as the time from study treatment initiation to death (of any cause).
  • 3-year overall survival [ Time Frame: 3 years ]
    Overall Survival (OS) is defined as the time from study treatment initiation to death (of any cause).
  • Safety profile independently for each arm: Common Terminology Criteria for Adverse event version 5 [ Time Frame: Throughout the treatment period, an expected average of 6 months ]
    Toxicity will be grade using the Common Terminology Criteria for adverse events version 5 and coded according to the standardized medical terminology MedDRA
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neoadjuvant Chemotherapy and Retifanlimab in Patients With Selected Retroperitoneal Sarcomas (TORNADO)
Official Title  ICMJE Randomized Phase II Study of Neoadjuvant Chemotherapy Plus Retifanlimab (INCMGA00012) in Patients With Selected Retroperitoneal Sarcomas
Brief Summary Multicenter, prospective, open-labeled, 2-arm, non-comparative randomized phase II trial to assess the antitumor activity of retifanlimab (INCMGA00012) in association with neoadjuvant chemotherapy
Detailed Description This is a multicenter, prospective, open-labeled, 2-arm, non-comparative randomized (1:1) phase II trial. Patients will be randomized between arm A (neodjuvant chemotherapy by doxorubicin + ifosfamide) and arm B (neodjuvant chemotherapy by doxorubicin + ifosfamide and retifanlimab) with one patient randomized in arm A for one patient randomized in arm B.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This is a multicenter, prospective, open-labeled, 2-arm, non-comparative randomized (1:1) phase II trial. Patients will be randomized between arm A (neodjuvant chemotherapy by doxorubicin + ifosfamide) and arm B (neodjuvant chemotherapy by doxorubicin + ifosfamide and retifanlimab) with one patient randomized in arm A for one patient randomized in arm B
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Retroperitoneal Sarcoma
  • Resectable Sarcoma
Intervention  ICMJE
  • Drug: Doxorubicin
    Doxorubicin will administered by intravenous infusion on day 1 every 3 weeks (75 mg/m²) up to 4 cycles
  • Drug: Ifosfamide
    Ifosfamide will be administered by intravenous infusion over 3 days every 3 weeks (9 g/m²) up to 4 cycles
  • Drug: INCMGA00012
    Retifanlimab will be administered by intravenous infusion on day 1every 3 weeks (375 mg) up to 4 cycles
    Other Name: Retifanlimab
Study Arms  ICMJE
  • Standard Arm A: treatment by neoadjuvant chemotherapy
    Treatment by doxorubicin and ifosfamide followed by surgery
    Interventions:
    • Drug: Doxorubicin
    • Drug: Ifosfamide
  • Experimental: Experimental Arm B: treatement by neoadjuvant chemotherapy and retifanlimab
    Treatment by doxorubicin, ifosfamide and retifanlimab followed by surgery
    Interventions:
    • Drug: Doxorubicin
    • Drug: Ifosfamide
    • Drug: INCMGA00012
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: July 13, 2021)
66
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2024
Estimated Primary Completion Date March 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients with retroperitoneal sarcoma histologically confirmed,
  2. For TLS status determination: available archived FFPE tumor tissue sample.
  3. Presence of mature tertiary lymphoid structures. Except if presence of TLS have been already confirmed by Biopathological platform at Bergonié Institute, presence of TLS should be confirmed by central review based on FFPE tumor tissue sample (archived or newly obtained by biopsy for research purpose).
  4. Non-metastatic and resectable disease,
  5. At least one lesion that can be biopsied for research purpose,
  6. No prior treatment for the disease under study,
  7. Age ≥ 18 years,
  8. ECOG ≤ 1,
  9. Life expectancy > 3 months,
  10. Patients must have measurable disease defined as per RECIST v1.1
  11. Adequate hematological, renal, metabolic and hepatic function
  12. Left ventricular ejection fraction ≥ 50% assessed by ECHO or MUGA within 6 months from study entry,
  13. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to study entry. .
  14. Both women and men must agree to use a highly effective method of contraception throughout the treatment period and for one year after discontinuation of treatment for women and 4 months for men.
  15. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, concomitant endometrial carcinoma stage IA grade 1, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,
  16. Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5),
  17. Voluntarily signed and dated written informed consent prior to any study specific procedure,
  18. Patients with a social security in compliance with the French law.

Exclusion Criteria:

  1. Previous treatment for retroperitoneal sarcoma including surgery, chemotherapy or radiotherapy
  2. Previous treatments with doxorubicin, daunorubicin, epirubicin, idarubicin and/or other anthracyclines or anthracenediones at the maximum cumulative dose,
  3. Known hypersensitivity to any involved study drug or any of its formulation components,
  4. Has an active or ongoing infection requiring systemic therapy,
  5. Known central nervous system malignancy (CNS),
  6. Women who are pregnant or breast feeding,
  7. Has known active hepatitis B or hepatitis C,
  8. Has a known history of Human Immunodeficiency Virus (HIV),
  9. Previous enrolment in the present study,
  10. Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons,
  11. Has received a live attenuated vaccine or a live vaccine within 30 days prior to the first dose of trial treatment, Note: the killed virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
  12. Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:

    1. Myocardial infarction or stroke/transient ischemic attack within the 6 months prior to study entry.
    2. Uncontrolled angina within the 3 months prior to study entry.
    3. Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes, or poorly controlled atrial fibrillation).
    4. Corrected QT (QTc) prolongation > 480 msec.
    5. History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association [NYHA] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled venous thrombus).
  13. Uncontrolled or significant renal disease including, but not limited to, any of the following:

    1. Acute or uncontrolled urinary infection at study entry,
    2. Hemorrhagic cystitis at study entry,
    3. Presence of blood on dipstick at study entry,
    4. Vesical atony,
    5. Known urinary tract obstruction.
  14. Patients with known history of active inflammatory bowel diseases, including those with small or large intestine inflammation, such as Crohn's disease or ulcerative colitis, will be excluded from the study,
  15. Has received systemic antibiotics within 14 days before the first dose of study treatment. Participants receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
  16. History of organ transplant, including allogeneic stem cell transplantation.
  17. Receiving probiotics as of the first dose of study treatment.
  18. Has an active autoimmune disease

    • Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible,
    • Patients requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at dose ≤ 10 mg or 10 mg equivalent prednisone day,
    • Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intra-ocular, intra-articular or inhalation) are acceptable.
  19. Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.
  20. Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy in the thoracic region that is > 30 Gy within 6 months of the first dose of study treatment. Note: Participants must have recovered from all radiation-related toxicities (to Grade >1 or baseline), not require corticosteroids for this purpose, and not have had radiation pneumonitis.
  21. Person under judicial protection or deprived of liberty.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Antoine ITALIANO, MD, PhD +33556333333 a.italiano@bordeaux.unicancer.fr
Contact: Simone MATHOULIN-PELISSIER, MD, PhD s.mathoulin@bordeaux.unicancer.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04968106
Other Study ID Numbers  ICMJE IB 2021-01
2021-001085-37 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Institut Bergonié
Study Sponsor  ICMJE Institut Bergonié
Collaborators  ICMJE Incyte Biosciences International Sàrl
Investigators  ICMJE Not Provided
PRS Account Institut Bergonié
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP