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M7824 in Subjects With HPV Associated Malignancies

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ClinicalTrials.gov Identifier: NCT03427411
Recruitment Status : Recruiting
First Posted : February 9, 2018
Last Update Posted : July 4, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

In the United States, each year there are more than 30,000 cases of human papillomavirus (HPV) associated cancers. Some of these cancers are often incurable and are not improved by standard therapies. Researchers want to see if a new drug M7824, which targets and blocks a pathway that prevents the immune system from effectively fighting the cancer can shrink tumors in people with some HPV cancers.

Objectives:

To see if the drug M7824 causes tumors to shrink.

Eligibility:

Adults age 18 and older who have a cancer associated with HPV infection.

Design:

Participants will be screened with medical history and physical exam. They will review their symptoms and how they perform normal activities. They will have body scans. They will give blood and urine samples. They will have a sample of their tumor tissue taken if one is not available.

Participants will have an electrocardiogram to evaluate their heart. Then they will get the study drug through a thin tube in an arm vein.

Participants will get the drug every 2 weeks for 26 times (1 year). This is 1 course.

After the course, participants will be monitored but will not take the study drug. If their condition gets worse, they will start another course with the drug. This process can be repeated as many times as needed.

Treatment will stop if the participant has bad side effects or the drug stops working.

Throughout the study, participants will repeat some or all the screening tests.

After participants stop taking the drug, they will have a follow-up visit and repeat some screening tests. They will get periodic follow-up phone calls.


Condition or disease Intervention/treatment Phase
Human Papilloma Virus Cervical Cancer Oropharyngeal Cancer Anal Cancer Vaginal or Penile Cancer Drug: M7824 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: M7824 in Subjects With HPV Associated Malignancies
Actual Study Start Date : February 27, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1
HPV associated cancer
Drug: M7824
Flat dose of 1,200 mg IV once every 2 weeks




Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: Every Six weeks ]
    The percentage of subjects that achieve an objective confirmed complete or partial overall tumor response using RECIST Version 1.1


Secondary Outcome Measures :
  1. duration of response [ Time Frame: disease progression ]
    The time from CR or PR (whichever is first recorded) until the first date that recurrent or PD is objectively documented

  2. overall survival (OS) [ Time Frame: death ]
    The time from the date of first treatment to the date of death

  3. progression-free survival time (PFS) [ Time Frame: disease progression or death ]
    The time from the date of first treatment to the date of disease progression or death

  4. disease control rate (DCR) [ Time Frame: 6 month ]
    The percentage of subjects that achieve an objective confirmed complete or partial overall tumor response using RECIST Version 1.1

  5. safety and tolerability of M7824 [ Time Frame: 30 days after treatment ]
    List of adverse event frequency



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITIERIA:
  • Age greater than or equal to 18 years.
  • Ability of subject to understand and the willingness to sign a written informed consent document.
  • Subjects with cytologically or histologically confirmed locally advanced or metastatic HPV associated malignancies including:

    • Non-Neuroendocrine Cervical cancers
    • P16+ Oropharyngeal cancers
    • Anal cancers
    • Vulvar, vaginal, penile, squamous cell rectal and neuroendocrine cervical cancers
  • Patients must have disease that is not amenable to potentially curative resection
  • Subjects must have measurable disease
  • ECOG performance status less than or equal to 1
  • Adequate hematologic function at screening, as follows:

    • Absolute neutrophil count (ANC) greater than or equal to 1 x 10^9/L
    • Hemoglobin greater than or equal to 9 g/dL
    • Platelets greater than or equal to 75,000/microliter.
  • Adequate renal and hepatic function at screening, as follows:

    • Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) greater than or equal to 40 mL/min according to the Cockcroft-Gault formula: CrCl= ((140-age) x (weight in kg) x (0.85, if female))/72 x Serum Creatinine (mg.dL)
    • Bilirubin less than or equal to 1.5 x ULN OR in subjects with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 x ULN
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x ULN, unless liver metastases are present, then values must be less than or equal to 3 x ULN)
  • The effects of M7824 on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and up to 120 days after the last dose of the drug. 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.
  • Patients serologically positive for HIV, Hep B, Hep C are eligible as long as the viral loads are undetectable by quantitative PCR. HIV positive patients must have CD4 count greater than or equal to 300 cells oer cubic millimeter at enrollment, be on stable antiretroviral therapy and have no reported opportunistic infections within 12 months prior to enrollment.

EXCLUSION CRITERIA:

-Pregnant women are excluded from this study because this drug has not been tested in pregnant women and there is f 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, breastfeeding should be discontinued if the mother is treated with M7824.

  • Patients with prior investigational drug, chemotherapy, immunotherapy or any prior radiotherapy (except for palliative bone directed therapy) within the past 28 days prior to the first drug administration except if the investigator has assessed that all residual treatment-related toxicities have resolved or are minimal and feel the patient is otherwise suitable for enrollment.
  • Major surgery within 28 days prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted).
  • Known intolerance to or life threatening side effects resulting from prior checkpoint inhibitor therapy.
  • Known active brain or central nervous system metastasis (less than 2 months out from definitive radiotherapy or surgery), seizures requiring anticonvulsant treatment (<3 months) or clinically significant cerebrovascular accident (<3 months). In order to be eligible patients must have repeat CNS imaging at least two months after definitive treatment showing stable CNS disease. Patients with evidence of intratumoral or peritumoral hemorrhage on baseline imaging are also excluded unless the hemorrhage is grade less than or equal to 1 and has been shown to be stable on two consecutive imaging scans.
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent with exception of:

    • diabetes type I, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease or other mild autoimmune disorders not requiring immunosuppressive treatment;
    • Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses less than or equal to 10 mg of prednisone or equivalent per day;
    • Administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable;
    • Subjects on systemic intravenous or oral corticosteroid therapy with the exception of physiologic doses of corticosteroids (less than or equal to the equivalent of prednisone 10 mg/day) or other immunosuppressives such as azathioprine or cyclosporin A are excluded on the basis of potential immune suppression. For these subjects these excluded treatments must be discontinued at least 1 weeks prior to enrollment for recent short course use (less than or equal to 14 days) or discontinued at least 4 weeks prior to enrollment for long term use (>14 days). In addition, the use of corticosteroids as premedication for contrastenhanced studies is allowed prior to enrollment and on study.
  • Subjects with a history of serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, or other illness considered by the Investigator as high risk for investigational drug treatment.
  • History of second malignancy within 3 years of enrollment except for the following: adequately treated non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer or other localized malignancy which has been adequately treated.
  • Known severe hypersensitivity reactions to monoclonal antibodies (Grade greater than or equal to 3 NCI CTCAE v4.03)
  • Receipt of any organ transplantation requiring ongoing immunosuppression.
  • Patients with vulvar cancer originating from differentiated vulvar intraepithelial neoplasia (d-VIN), as opposed to vulvar intraepithelial neoplasia of usual type, are excluded. Vulvar squamous cell carcinoma originating from differentiated VIN (d-VIN) is HPV negative; however, rare cases of HPV positive d-VIN can occur. Patients are not excluded if their tumor has tested positive for HPV or there is no documentation of prior VIN type.

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): NCT03427411


Contacts
Contact: Cynthia Boyle, R.N. (240) 760-6006 helsabec@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
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
Principal Investigator: Julius Y Strauss, M.D. National Cancer Institute (NCI)

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03427411     History of Changes
Other Study ID Numbers: 180056
18-C-0056
First Posted: February 9, 2018    Key Record Dates
Last Update Posted: July 4, 2018
Last Verified: April 23, 2018

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) ):
TGFR1 pathway signaling and overexpression
PD-1 inhibitors
Manageable Safety Profile
Bifunctional Fusion Protein
Refractory/Recurrent HPV Associated Malignancies

Additional relevant MeSH terms:
Anus Diseases
Neoplasms
Uterine Cervical Neoplasms
Papilloma
Anus Neoplasms
Oropharyngeal Neoplasms
Penile Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Pharyngeal Diseases