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Maintenance Treatment With Bevacizumab and Atezolizumab for Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04510584
Recruitment Status : Not yet recruiting
First Posted : August 12, 2020
Last Update Posted : August 12, 2020
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Ovarian Endometrioid Tumor Fallopian Tube Cancer Primary Peritoneal Cancer TP53 Mutation Drug: Atezolizumab Drug: Bevacizumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Halting Early Advancement of Residual Disease by Treatment With Bevacizumab and Atezolizumab in Ovarian Cancer
Estimated Study Start Date : September 28, 2020
Estimated Primary Completion Date : September 28, 2023
Estimated Study Completion Date : September 28, 2023


Arm Intervention/treatment
Experimental: Atezolizumab and Bevacizumab

A 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.

Drug: Atezolizumab
Atezolizumab is a humanized immunoglobulin (IgG1) monoclonal antibody that targets programmed death-ligand 1 (PD-L1) on tumor-infiltrating immune cells (ICs) or tumor cells (TCs) and prevents interaction with the programmed death-1 (PD-1) receptor and B7.1 (CD80), both of which function as inhibitory receptors expressed on T cells and other immune cells.
Other Name: TECENTRIQ

Drug: Bevacizumab
Bevacizumab is a recombinant humanized IgG1 monoclonal antibody that binds VEGF, a secreted factor that stimulates angiogenesis. Bevacizumab prevents the interaction of VEGF with its receptors and neutralizes the biological activity of VEGF.
Other Name: AVASTIN




Primary Outcome Measures :
  1. Number of participants where increase in circulating deoxyribonucleic acid (ctDNA) level is related to progression [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. Disease free survival rate [ Time Frame: 6 months ]
  2. Disease free survival rate [ Time Frame: 12 months ]
  3. Progression free survival rate [ Time Frame: 1 year ]
  4. Progression free survival rate [ Time Frame: 2 years ]
  5. Number of participants with disease free survival with change from detectable to undetectable TP53 ctDNA [ Time Frame: 6 months ]
  6. Number of participants with disease free survival with change from detectable to undetectable TP53 ctDNA [ Time Frame: 12 months ]
  7. Number of participants with adverse events [ Time Frame: 3 years ]


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:   Female
Accepts Healthy Volunteers:   No
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.

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): NCT04510584


Contacts
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Contact: Stephanie Lheureux, M.D. 4169462818 stephanie.lheureux@uhn.ca

Locations
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Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Contact: Stephanie Lheureux, M.D.    416-946-2818      
Principal Investigator: Stephanie Lheureux, M.D.         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
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Principal Investigator: Stephanie Lheureux, M.D. Princess Margaret Cancer Centre
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04510584    
Other Study ID Numbers: HEARTBEAT-OV
20-5562 ( Other Identifier: University Health Network )
First Posted: August 12, 2020    Key Record Dates
Last Update Posted: August 12, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Fallopian Tube Neoplasms
Neoplasms by Site
Neoplasms
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Fallopian Tube Diseases
Bevacizumab
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors