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TGF-beta Trap (M7824) and NHS-IL12 (M9241) Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies

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ClinicalTrials.gov Identifier: NCT04235777
Recruitment Status : Not yet recruiting
First Posted : January 22, 2020
Last Update Posted : May 29, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Genitourinary cancers are some of the most common types of cancer. They are lethal when they spread. The drug M7824 blocks the paths that cancer cells use to stop the immune system from fighting cancer. The drug M9241 triggers the immune system to fight cancer. Researchers want to learn if these drugs can help fight these cancers when given with and without Stereotactic Body Radiation Therapy (SBRT) radiation.

Objective:

To learn if M7824 and M9241, with or without SBRT, can help the immune system to fight cancer better.

Eligibility:

People 18 and older with cancer that started in the bladder, kidneys, or other genitourinary organs (but not the prostate) and has spread to other parts of the body.

Design:

Participants will be screened with:

medical history

physical exam

ability to do their normal activities

blood tests

urine tests

electrocardiogram

body scans.

Participants will give a tumor sample or have a tumor biopsy.

Screening tests will be repeated during the study.

Participants will get M9241. It is injected under the skin every 4 weeks. They will also get M7824 through an intravenous (IV) infusion every 2 weeks. For this, a small plastic tube is put into a vein in the arm. They will get these drugs in 28-day cycles until they leave the study. They may have SBRT.

Participants will give tissue and saliva samples.

Participants will have a follow-up visit 30 days after treatment ends. Then they will get phone calls or emails every 12 weeks indefinitely.


Condition or disease Intervention/treatment Phase
Urothelial Cancer Bladder Cancer Genitourinary Cancer Urogenital Neoplasms Urogenital Cancer Drug: M7824 Drug: M9241 Radiation: Stereotactic body radiation therapy (SBRT) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of TGF-Beta Trap (M7824) and NHS-IL12 (M9241) Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies
Estimated Study Start Date : June 3, 2020
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : April 1, 2022


Arm Intervention/treatment
Experimental: Arm 1
Treatment with M7824 and deescalating doses of M9241 if appropriate
Drug: M7824
1200 mg administered IV every two weeks while on M9241 and with or without SBRT

Drug: M9241
An initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT

Experimental: Arm 2
Treatment with M7824 and deescalating doses of M9241 (if appropriate) with sequential SBRT
Drug: M7824
1200 mg administered IV every two weeks while on M9241 and with or without SBRT

Drug: M9241
An initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT

Radiation: Stereotactic body radiation therapy (SBRT)
A fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and M9241

Experimental: Arm 3
Treatment with M7824 and deescalating doses of M9241 (if appropriate) with concurrent SBRT
Drug: M7824
1200 mg administered IV every two weeks while on M9241 and with or without SBRT

Drug: M9241
An initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT

Radiation: Stereotactic body radiation therapy (SBRT)
A fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and M9241




Primary Outcome Measures :
  1. safety and tolerability of M9241 and M7824 aone or in combination with SBR [ Time Frame: until confirmed progression, unacceptable toxicity or trial withdrawal ]
    -The fraction of patients with toxicity noted at each dose level will be reported by grade and type of toxicity identified.-Maximum tolerated dose will also be reported.


Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: From time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented ]
    the fraction of evaluable patients with a PR or CR at the end of treatment with M7824 will be reported along with 80% and 95% two-sided confidence intervals for each arm

  2. Progression free survival (PFS) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first ]
    duration of time from start of treatment to time of progression or death, whichever occurs first

  3. Overall Survival (OS) [ Time Frame: Time from treatment to the date of death from any cause ]
    Time from the start of treatment that patients are still alive.



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
  • INCLUSION CRITERIA:
  • Patients must have histologically or cytologically confirmed diagnosis of a metastatic non-prostate genitourinary tumor.
  • Patients must have metastatic disease defined as new or progressive lesions on cross-sectional imaging. Radiological evaluation should occur within 21 days prior to enrollment.
  • Patient must have evaluable or measurable disease.
  • Patients in Arms 2 and 3 must have at least one site of disease that is amenable to irradiation (irradiation of up to 4 different sites is permitted)
  • Patients must have at least one measurable site of disease that will not be irradiated.
  • Patients may have been previously treated with cytotoxic chemotherapy regimen or targeted agent. Patients may have received any number of prior cytotoxic agents.
  • Patients may have been previously treated with radiation therapy. However, re-irradiation of a previously irradiated site is not permitted unless explicitly discussed with protocol PI and treating radiation oncologist.
  • Patients may have had prior immunomodulating therapy including therapy with a checkpoint inhibitor but excluding prior treatment with M7824 and/or M9241.
  • Pre-treatment tissue availability (collected less than or equal to 1 year) for PD-L1 expression is mandatory for enrollment. If tissue is determined to be of insufficient/unsuitable quality/quantity, a pre-treatment biopsy prior to initiation of study therapy will be required.
  • Male and female participants who are at least 18 years of age on the day of signing the informed consent will be enrolled in the study.
  • ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%)

    • Patients must have normal organ and marrow function as defined below:
    • leukocytes greater than or equal to 2500mcL
    • absolute neutrophil count greater than or equal to 1200/mcL
    • platelets greater than or equal to 100,000/mcL
    • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal
    • Hgb greater than or equal to 9g/dL (pRBC transfusions are allowed to achieve acceptable Hgb)
  • Patients may have mild to moderate hepatic impairment with total bilirubin less than or equal to 3.0 (SqrRoot) ULN.
  • For patients with liver involvement in their tumor, we allow the following: AST less than or equal to 5.0 (SqrRoot) ULN, ALT less than or equal to 5.0 (SqrRoot) ULN, and bilirubin less than or equal to 3.0 (SqrRoot) ULN.
  • Calculated Creatinine clearance greater than or equal to 20 mL/min (using either CKD-EPY equation)
  • The effects of M7824 and/or M9241 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use strict and effective contraception during treatment and for at least 4 months after the last dose of M7824 administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • HIV-positive patients are eligible if on stable dose of highly active antiretroviral therapy (HAART), CD4 counts are greater than 350 cells/mm3 and viral load is undetectable.
  • Patients with previously treated brain or CNS metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring steroids, and any whole brain radiation therapy was completed at least 2 weeks prior to M7824 administration, or any stereotactic radiosurgery was completed at least 2 weeks prior to M7824 administration.
  • HBV positive patients are eligible-they must have been treated and on a stable dose of antivirals [eg, entecavir, tenofovir, or lamivudine; (adefovir or interferon are not allowed)] at study entry and with planned monitoring and management according to appropriate labeling guidance.
  • HCV positive patients are eligible if participants are on active HCV therapy at study entry and must be on a stable dose without documented clinically significant impaired liver function test or hematologic abnormalities and with planned monitoring and management according to appropriate labeling guidance.
  • Ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to M7824 and/or M9241 investigational agents used in the study.
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients with a history of bleeding diathesis or recent clinically significant bleeding events considered by the Investigator as high risk for investigational drug treatment are also excluded with the exception of hematuria.
  • Pregnant women are excluded from this study because M7824 and/or M9241 are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M7824 and/or M9241, breastfeeding should be discontinued if the mother is treated with these agents.
  • Patients with any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (>10 mg daily prednisone equivalent) or immunosuppressive medications except inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Patients with any active or recent history of inflammatory bowel disease, active lupus or scleroderma or other medical conditions (i.e pneumonits with planned SBRT to lung lesion) or genetic radiosensitivity syndromes will be excluded from the study unless deemed eligible by Principal Investigator because these diseases make the subject unsafe or ineligible for radiation therapy with SBRT.
  • Patients with prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast or low risk Gleason 6 prostate cancer.
  • Patients having tumor lesion(s) in the liver or chest which are 10 cm or larger.

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): NCT04235777


Contacts
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Contact: Lisa Ley, R.N. (240) 760-6097 lisa.ley@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Andrea B Apolo, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04235777    
Other Study ID Numbers: 200012
20-C-0012
First Posted: January 22, 2020    Key Record Dates
Last Update Posted: May 29, 2020
Last Verified: March 26, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Immunocytokine
Renal Cell Carcinoma
Urothelial Cancinoma
Immune Therapy
Additional relevant MeSH terms:
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Urogenital Neoplasms
Neoplasms
Neoplasms by Site