Clinical Trials /

Maintenance Treatment With Bevacizumab and Atezolizumab for Ovarian Cancer

NCT04510584

Description:

This study is being done to look at the combination of the drugs atezolizumab and bevacizumab as a maintenance treatment (treatment given after the main treatment to keep the cancer from coming back or worsening) following standard therapy in patients with high grade ovarian, fallopian tube, or primary peritoneal cancer with a mutation (change) in a gene called TP53. Genes are molecules in the body that are made up of deoxyribonucleic acid (DNA) and control how the body's cells behave.

Related Conditions:
  • Fallopian Tube Endometrioid Adenocarcinoma
  • High Grade Fallopian Tube Serous Adenocarcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Primary Peritoneal Endometrioid Adenocarcinoma
  • Primary Peritoneal Serous Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Maintenance Treatment With Bevacizumab and Atezolizumab for Ovarian Cancer
  • Official Title: Halting Early Advancement of Residual Disease by Treatment With Bevacizumab and Atezolizumab in Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: HEARTBEAT-OV
  • SECONDARY ID: 20-5562
  • NCT ID: NCT04510584

Conditions

  • Ovarian Endometrioid Tumor
  • Fallopian Tube Cancer
  • Primary Peritoneal Cancer
  • TP53 Mutation

Interventions

DrugSynonymsArms
AtezolizumabTECENTRIQAtezolizumab and Bevacizumab
BevacizumabAVASTINAtezolizumab and Bevacizumab

Purpose

This study is being done to look at the combination of the drugs atezolizumab and bevacizumab as a maintenance treatment (treatment given after the main treatment to keep the cancer from coming back or worsening) following standard therapy in patients with high grade ovarian, fallopian tube, or primary peritoneal cancer with a mutation (change) in a gene called TP53. Genes are molecules in the body that are made up of deoxyribonucleic acid (DNA) and control how the body's cells behave.

Detailed Description

      Atezolizumab and bevacizumab are a type of drug called a monoclonal antibody. Antibodies are
      proteins that are naturally found in the blood stream that fight infections. A monoclonal
      antibody is a special kind of antibody that is created in a laboratory that seeks out
      specific proteins in the body that may be involved in cancers to stop tumor growth.

      When tumor cells start to die, broken down pieces of the tumor's DNA gets released into the
      blood stream, called circulating tumor DNA (ctDNA). Looking at ctDNA may be useful in
      determining whether the cancer is responding to treatment.

      The purpose of this research study is to see whether looking at tumor DNA circulating in the
      bloodstream can help to determine which patients may respond to atezolizumab and bevacizumab
      and whether this drug combination is useful, when given as a maintenance treatment for
      patients with TP53 mutant ovarian, fallopian tube, or primary peritoneal cancer.
    

Trial Arms

NameTypeDescriptionInterventions
Atezolizumab and BevacizumabExperimentalA cycle will be every 3 weeks. Atezolizumab will be given intravenously (by vein) at a dose of 1200 mg once every cycle. Bevacizumab will be given intravenously at a dose of 15 mg/kg once every cycle. Up to 17 cycles of study treatment may be given. Participants may be able to receive the study treatment for more than 17 cycles if the participants and the study doctor thinks that they are benefiting.
  • Atezolizumab
  • Bevacizumab

Eligibility Criteria

        Inclusion Criteria:

        Pre-screening:

          -  Patients must have histologically confirmed TP53-mutant high grade serous or high
             grade endometrioid ovarian, fallopian tube, primary peritoneal cancer.

          -  Ability to understand and the willingness to sign a written Pre-screening Informed
             consent document.

          -  Patients must be receiving standard therapy for recurrent disease and have completed 3
             cycles of platinum-based chemotherapy, with clinical benefit (in opinion of
             investigator). Patients with stable disease (in opinion of investigator) after 3
             cycles of chemotherapy will also be eligible for pre-screening. There is no limitation
             on the number of prior lines of therapy. May have received prior PARP-inhibitor
             therapy or prior bevacizumab or biosimilar.

          -  Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer must be
             available.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤2

          -  Patients must have a life expectancy ≥16 weeks

        Main Study:

          -  Patients must have histologically confirmed TP53-mutant high grade serous or high
             grade endometrioid ovarian, fallopian tube, primary peritoneal cancer.

          -  Must have completed standard therapy for recurrent disease including at least 4 cycles
             of platinum-based chemotherapy with no clinical and radiographic evidence of disease
             progression on the post-treatment scan or a rising CA-125 level, following completion
             of standard therapy. Patients with stable disease and in response (as per
             Investigators opinion) following completion of chemotherapy will also be eligible for
             this study. There is no limitation on the number of prior lines of therapy.

          -  Following completion of platinum-based chemotherapy, patients must have residual
             disease detectable by TP53 ctDNA

          -  May have received prior PARP-inhibitor therapy or prior bevacizumab.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤2

          -  Patients must have a life expectancy ≥16 weeks

          -  Patients must have normal organ and marrow function

          -  Ongoing prior toxicities related to previous treatments must be recovered to ≤ grade 2
             at the time of registration

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Patients must receive first dose of study treatment within 8 weeks after their last
             dose of platinum based chemotherapy (last dose is the day of the last infusion)

          -  Postmenopausal or evidence of non-childbearing status for women of childbearing
             potential. Female patients of childbearing potential should use highly effective
             contraception and take active measures to avoid pregnancy while undergoing
             atezolizumab treatment and for at least 5 months after the last dose.

          -  Willing and able to comply with the protocol for the duration of the study including
             undergoing treatment and scheduled visits and examinations

          -  Formalin fixed, paraffin embedded (FFPE) tumor sample from the primary cancer must be
             available.

          -  Pre-treatment CA-125 measurements must meet specific criterion

        Exclusion Criteria:

        Pre-screening:

          -  History of severe allergic reactions attributed to compounds of similar chemical or
             biologic composition to bevacizumab, or atezolizumab

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             severe infection, symptomatic congestive heart failure, or psychiatric illness/social
             situations that (in the opinion of Investigator) would limit compliance with study
             requirements.

          -  History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
             within 6 months prior to day 1.

        Main Study:

          -  Patients who are receiving any other investigational agents or on-going chemotherapy.

          -  History of severe allergic reactions attributed to compounds of similar chemical or
             biologic composition to bevacizumab, or atezolizumab

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             severe infection, symptomatic congestive heart failure, or psychiatric illness/social
             situations that (in the opinion of Investigator) would limit compliance with study
             requirements.

          -  History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
             within 6 months prior to day 1.

          -  Invasive procedures defined as follows:

               -  Major surgical procedure or significant traumatic injury within 28 days prior to
                  Day 1 therapy, or open biopsy within 28 days prior to Day 1 therapy

               -  Anticipation of need for major surgical procedures during the course of the study

          -  Significant vascular disease within 6 months prior to Day 1

          -  Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because of the possible increased risk of bleeding
             if treatment with antiangiogenic agents is provided.

          -  Inadequately controlled hypertension, history of cerebrovascular accident, myocardial
             infarction or unstable angina, serious or inadequately controlled cardiac arrhythmia
             within 6 months.

          -  Patients with known hypersensitivity to Chinese hamster ovary cell products or other
             recombinant human antibodies.

          -  Resting ECG with QTcF > 470 msec or family history of long QT syndrome.

          -  History of bowel obstruction within 28 days from proposed start of treatment.

          -  History or evidence of arterial thrombotic or hemorrhagic disorders within 3 months
             before proposed start of treatment, non-healing wound, ulcer, or bone fracture.

          -  Known active HIV or hepatitis B or C infection

          -  Other malignancy within the last 3 years except: adequately treated non-melanoma skin
             cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ
             (DCIS), Stage 1, grade 1 endometrial carcinoma, or other solid tumours including
             lymphomas (without bone marrow involvement) curatively treated with no evidence of
             disease for ≥5 years. Patients with a history of localised breast cancer may be
             eligible, provided they completed their adjuvant chemotherapy more than three years
             prior to registration, and that the patient remains free of recurrent or metastatic
             disease

          -  Patients should be excluded if they have had prior treatment with anti-CTLA-4 antibody
             or any other antibody or drug specifically targeting T-cell co-stimulation. Previous
             treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 is not allowed.

          -  The patient has experienced any of the following:

               -  The patient has radiographic evidence of cavitating pulmonary lesion(s).

               -  The patient has tumour invading or encasing any major blood vessels.

               -  The patient has evidence of tumour invading the GI tract (esophagus, stomach,
                  small or large bowel, rectum or anus), or any evidence of endotracheal or
                  endobronchial tumour within 28 days before the first dose of study treatment

               -  Patient with extensive pelvic mass at risk of fistulization, or history

               -  Active peptic ulcer disease within 28 days before the first dose of study
                  treatment.

               -  Inflammatory bowel disease (including ulcerative colitis and Crohn's disease),
                  diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis

               -  Malabsorption syndrome

               -  Other disorders associated with a high risk of fistula formation including PEG
                  tube placement.

          -  Clinically significant gastrointestinal bleeding within 6 months before the first dose
             of study treatment

          -  Administration of a live vaccine within 4 weeks prior to start of protocol therapy.

          -  Patients with diagnosis of immunodeficiency or who are receiving systemic steroid
             therapy or any other form of immunosuppressive therapy within 7 days prior to the
             first dose of trial treatment. The following are exceptions to this exclusion
             criteria: intranasal, inhaled, topical steroids, or local steroids injections (e.g.
             intra-articular injection); systemic corticosteroids at physiologic dose not to exceed
             10 mg/day of prednisone or equivalent; steroids as premedication for hypersensitivity
             reactions (eg, CT scan premedication).

          -  History of autoimmune disease, such as, but not restricted to: rheumatoid arthritis,
             inflammatory bowel disease, systemic lupus erythematous, ankylosing spondylitis,
             scleroderma, or multiple sclerosis requiring treatment within the last two years.
             Patients with vitiligo or diabetes are not excluded. Replacement therapy (e.g.
             thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or
             pituitary insufficiency, etc.) is not considered a form of systemic treatment.
             Patients with recent history of thyroiditis.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants where increase in circulating deoxyribonucleic acid (ctDNA) level is related to progression
Time Frame:3 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease free survival rate
Time Frame:6 months
Safety Issue:
Description:
Measure:Disease free survival rate
Time Frame:12 months
Safety Issue:
Description:
Measure:Progression free survival rate
Time Frame:1 year
Safety Issue:
Description:
Measure:Progression free survival rate
Time Frame:2 years
Safety Issue:
Description:
Measure:Number of participants with disease free survival with change from detectable to undetectable TP53 ctDNA
Time Frame:6 months
Safety Issue:
Description:
Measure:Number of participants with disease free survival with change from detectable to undetectable TP53 ctDNA
Time Frame:12 months
Safety Issue:
Description:
Measure:Number of participants with adverse events
Time Frame:3 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University Health Network, Toronto

Last Updated

August 9, 2020