Clinical Trials /

Decitabine Treatment in HPV-Induced Anogenital and Head and Neck Cancer Patients After Radiotherapy or as Novel Late Salvage

NCT04252248

Description:

Open-label, single-center phase I study to evaluate first signs of efficacy and to confirm the safety and tolerability of a decitabine safe-dose treatment in two strata of patients with HPV induced anogenital and head and neck cancers (Stratum 1: patients with high rist for disease recurrence; Stratum 2: patients with failure of standard therapy). The study is expected to enroll 18 patients overall (9 patients in each stratum). The duration of the trial for each patient is expected to be 6 months (two 28 day cycles of study treatment plus four months of additional follow-up). The overall duration of the trial is expected to be approximately 42 months.

Related Conditions:
  • Anal Carcinoma
  • Cervical Carcinoma
  • Malignant Uterine Neoplasm
  • Oral Cavity Carcinoma
  • Oropharyngeal Carcinoma
  • Penile Carcinoma
  • Vaginal Carcinoma
  • Vulvar Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Decitabine Treatment in HPV-Induced Anogenital and Head and Neck Cancer Patients After Radiotherapy or as Novel Late Salvage
  • Official Title: Decitabine Treatment in HPV-Induced Anogenital and Head and Neck Cancer Patients After Radiotherapy or as Novel Late Salvage (DERANO)

Clinical Trial IDs

  • ORG STUDY ID: NCT-2014-0250
  • NCT ID: NCT04252248

Conditions

  • Head and Neck Cancer
  • Anogenital Cancer

Interventions

DrugSynonymsArms
DacogenStratum 1

Purpose

Open-label, single-center phase I study to evaluate first signs of efficacy and to confirm the safety and tolerability of a decitabine safe-dose treatment in two strata of patients with HPV induced anogenital and head and neck cancers (Stratum 1: patients with high rist for disease recurrence; Stratum 2: patients with failure of standard therapy). The study is expected to enroll 18 patients overall (9 patients in each stratum). The duration of the trial for each patient is expected to be 6 months (two 28 day cycles of study treatment plus four months of additional follow-up). The overall duration of the trial is expected to be approximately 42 months.

Trial Arms

NameTypeDescriptionInterventions
Stratum 1ExperimentalPatients having received standard, definitive chemoradiotherapy according to current, national guidelines with curative intent and being at high risk for disease recurrence (patients are considered at high risk if they display a positive nodal status of their cancer (anogenital HPV-induced tumor) or if the tumor is locally advanced and/or if they display a positive nodal status with extracapsular extension (head and neck HPV-induced tumor). Study therapy (as additional therapy to standard chemoradiation) will start after a time interval of 6-8 weeks after finishing chemoradiotherapy
  • Dacogen
Stratum 2ExperimentalPatients with non-curative and progressive disease having received all standard, national approved systemic therapies (according to current, national guidelines with regard to the specific tumor entity), and/or presently not eligible for a respective therapy, and/or refused respective therapy. Study treatment thereby represents a potential palliative, "last-line" systemic therapy option (late salvage).
  • Dacogen

Eligibility Criteria

        Inclusion Criteria:

        1. Patients meeting all of the following criteria will be considered for admission to the
        trial: Patients with an HPV-induced (will be assumed if both HPV DNA and
        immunohistochemical overexpression of p16INK4a is detected in tumor tissue) cancer of the

          -  anus

          -  vulva

          -  vagina

          -  uterine

          -  cervix

          -  penis or

          -  oropharynx/oral cavity and

               -  Stratum 1: Patients having received standard, definitive chemoradiotherapy
                  according to current national guidelines with curative intent and being at high
                  risk for disease recurrence (patients are considered at high risk if they display
                  a positive nodal status of their cancer (anogenital HPV-induced tumor) or if the
                  tumor is locally advanced and/or if they display a positive nodal status with
                  extracapsular extension (head and neck HPV-induced tumor). Study therapy (as
                  additional therapy to standard chemoradiation) will start after a time interval
                  of 6-8 weeks after finishing chemoradiotherapy.

               -  Stratum 2: Patients with non-curative and progressive disease having received all
                  standard, national approved systemic therapies (according to current, national
                  guidelines with regard to the specific tumor entity), and/or presently not
                  eligible for a respective therapy, and/or refused respective therapy. Study
                  treatment thereby represents a potential palliative, "last-line" systemic therapy
                  option (late salvage).

          -  Ability of patient to understand character and individual consequences of the clinical
             trial

          -  Postmenopausal or evidence of non-childbearing status. For women of childbearing
             potential: negative urine pregnancy test at baseline and highly effective forms of
             contraception (see 6.5) in place thereafter as well as confirmed negative urine
             pregnancy test prior to treatment on day 1 of every cycle and at end of treatment
             period Evidence of childbearing potential is defined as:

               -  Fertile, following menarche and until becoming post-menopausal unless permanently
                  sterile Postmenopausal or evidence of non-childbearing status is defined as: o
                  Amenorrheic for 1 year or more without an alternative medical cause following
                  cessation of exogenous hormonal treatments PLUS Follicle stimulating hormone
                  (FSH) levels in the postmenopausal range in women not using hormonal
                  contraception or hormonal replacement therapy

               -  Surgical sterilisation (bilateral oophorectomy, hysterectomy or bilateral
                  salpingectomy) A man is considered fertile after puberty unless permanently
                  sterile by bilateral orchidectomy.

          -  Female patients of child bearing potential and male patients with partners of child
             bearing potential, who are sexually active, must agree to the use of highly effective
             forms of contraception. This should be started from the signing of the informed
             consent and continue throughout period of taking study treatment and for 6 months
             (female study participants)/ 3 months (male study participants) after last dose of
             study drug.

          -  Evidence of a personally signed and dated informed consent document indicating that
             the patient (or a legally acceptable representative) has been informed of all
             pertinent aspects of the study (must be given before enrolment in the trial)

          -  Patients who are willing and able to comply with scheduled visits, treatment plan,
             laboratory tests, and other study procedures.

        Exclusion Criteria:

        Patients presenting with any of the following criteria will not be included in the trial:

          -  Age <18 years

          -  Grade 3 neutropenia with Neutrophiles < 1/nl, thrombocytopenia with thrombocytes <
             50/nl and/ or anemia with Hgb <8.0 g/dL

          -  Active infections requiring anti-infective treatment

          -  Bleeding disorders (e.g. Hemophilia, von Willebrandt disease, congestive deficiency of
             any coagulation factor (e.g. factor V, X), Immune thrombocytopenia (ITP)
             thrombocytopathies (e.g. Bernard-Soulier-syndrome drug induced bleeding disorders

          -  Insulin-dependent and unregulated diabetes

          -  Grade 3/4 renal failure with a GFR < 60 ml/min

          -  Liver cirrhosis Child C • History of cardiac diseases

          -  Pregnancy and/ or lactation • History of treatment with DNA Methyltransferase
             Inhibitors (DNMTs)

          -  Participation in other clinical trials involving another investigational agent within
             4 weeks prior to first treatment of this study

          -  ECOG performance status >2

          -  History of hypersensitivity to the investigational medicinal product or to any drug
             with similar chemical structure or to any excipient present in the pharmaceutical form
             of the investigational medicinal product

          -  History of other malignancies (except basal cell carcinoma) in the past 5 years No
             patient will be allowed to enroll in this trial more than once.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLT)
Time Frame:56 days
Safety Issue:
Description:The primary objective of the study is to evaluate the safety and tolerability of decitabine treatment in two strata of patients with HPV-induced anogenital and head and neck cancer. Primary endpoint is the incidence of dose limiting toxicities (DLT) during the first two cycles of study treatment (up to day 56). DLT will be assessed and managed independently for both strata.

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:6 months
Safety Issue:
Description:The Overall Response Rate (or Objective Response Rate) is defined as the proportion of patients achieving a complete (CR) or partial (PR) response in their overall response assessment according to RECIST v1.1 measured at the 6 months staging vs baseline.
Measure:Disease Control Rate (DCR)
Time Frame:6 months
Safety Issue:
Description:The Disease Control Rate (DCR) is defined as the proportion of patients achieving stable disease or a better outcome (CR, PR, SD) in their overall response assessment according to RECIST v1.1 measured at the 6 months staging vs baseline.
Measure:Quality of Life
Time Frame:week 3, 5, 8 and 24
Safety Issue:
Description:Quality-of-Life (QoL) will be assessed by the EORTC Quality of Life Core Questionnaire (QLQ30), supplemented by information on self-assessed concomitant diseases and demographics. QoL will be assessed at baseline, and at week 3, 5, 8 and 24 (EOS)
Measure:Overall Survival (OS)
Time Frame:from admission until Last Patient Last Visit (LPLV), assessed ≥ 6 months
Safety Issue:
Description:OS is defined as the time from admission to the study until death from any cause. Patients who are alive at the end of the study are censored on the day of last contact.
Measure:Progression-free Survival (PFS)
Time Frame:from admission until Last Patient Last Visit (LPLV), assessed ≥ 6 months
Safety Issue:
Description:PFS is defined as the time from admission to the study until progression of disease or death from any cause, whichever occurs first. Patients who are alive and did not have progression of disease at the end of the study are censored on the day of last contact.
Measure:Overall Response Rate
Time Frame:3 months
Safety Issue:
Description:The ORR-3m is defined as the proportion of patients achieving a complete (CR) or partial (PR) response in their overall response assessment according to RECIST v1.1 measured at the 3 months staging vs baseline.
Measure:Disease Control Rate
Time Frame:3 months
Safety Issue:
Description:The DCR-3m is defined as the proportion of patients achieving stable disease or a better outcome (CR, PR, SD) in their overall response assessment according to RECIST v1.1 measured at the 3 months staging vs baseline.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University Hospital Heidelberg

Last Updated

January 31, 2020