Ovarian Endometrioid TumorPhase 2NCT04510584
Maintenance Treatment With Bevacizumab and Atezolizumab for Ovarian Cancer
A Phase 2 study testing Atezolizumab and Bevacizumab in people with Ovarian Endometrioid Tumor and Fallopian Tube Cancer, run by University Health Network, Toronto at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Endometrioid Tumor, Fallopian Tube Cancer, Primary Peritoneal Cancer
- What is being tested?
- Atezolizumab and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- 16 Jul 2021to 22 Feb 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Halting Early Advancement of Residual Disease by Treatment With Bevacizumab and Atezolizumab in Ovarian Cancer
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.
Read the 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.
- Conditions
- Ovarian Endometrioid Tumor, Fallopian Tube Cancer, Primary Peritoneal Cancer, TP53 Mutation
- Being tested
- Atezolizumab, Bevacizumab
- Medical subject headings
- Fallopian Tube Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabDrug
Also called TECENTRIQ
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.
BevacizumabDrug
Also called AVASTIN
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.
| Study group | Role | What they receive |
|---|---|---|
| Atezolizumab and Bevacizumab | Experimental | 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. Receives: Drug: Atezolizumab; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants where increase in circulating deoxyribonucleic acid (ctDNA) level is related to progression
Measured: 3 months
Secondary outcomes (7)
Disease free survival rate
Measured: 6 months
Disease free survival rate
Measured: 12 months
Progression free survival rate
Measured: 1 year
Progression free survival rate
Measured: 2 years
Number of participants with disease free survival with change from detectable to undetectable TP53 ctDNA
Measured: 6 months
Number of participants with disease free survival with change from detectable to undetectable TP53 ctDNA
Measured: 12 months
Number of participants with adverse events
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2020
- Study start16 Jul 2021
- Primary completion22 Feb 2023
- Study completion22 Feb 2023
Why it stopped: 19 patients screenfailed, stopping recruitment before first patient enrollment to analyze pilot results from screening samples.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian Endometrioid TumorStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stephanie Lheureux, M.D., Principal investigator, Princess Margaret Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04510584
- Sponsor's protocol ID
- HEARTBEAT-OV
- Other IDs
- 20-5562
- Status last verified
- Jun 2023
- First submitted
- 9 Aug 2020
- Last updated
- 6 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Halting Early Advancement of Residual Disease by Treatment With Bevacizumab and Atezolizumab in Ovarian Cancer
- ClinicalTrials.gov ID
- NCT04510584
- Acronym / sponsor ID
- HEARTBEAT-OV
- Conditions
- Ovarian Endometrioid Tumor, Fallopian Tube Cancer, Primary Peritoneal Cancer, TP53 Mutation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: 19 patients screenfailed, stopping recruitment before first patient enrollment to analyze pilot results from screening samples.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 16 Jul 2021 (actual)
- Primary completion
- 22 Feb 2023 (actual)
- Study completion
- 22 Feb 2023 (actual)
- First posted
- 12 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Atezolizumab and Bevacizumab | Experimental | Drug: Atezolizumab, Drug: BevacizumabA 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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
Key exclusion criteria (35 listed)
- 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.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtezolizumabAlso: TECENTRIQAtezolizumab 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. | Drug | Atezolizumab and Bevacizumab |
| BevacizumabAlso: AVASTINBevacizumab 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. | Drug | Atezolizumab and Bevacizumab |
Primary outcome
Number of participants where increase in circulating deoxyribonucleic acid (ctDNA) level is related to progression
Time frame: 3 months
7 secondary outcomes
Disease free survival rate
Time frame: 6 months
Disease free survival rate
Time frame: 12 months
Progression free survival rate
Time frame: 1 year
Progression free survival rate
Time frame: 2 years
Number of participants with disease free survival with change from detectable to undetectable TP53 ctDNA
Time frame: 6 months
Number of participants with disease free survival with change from detectable to undetectable TP53 ctDNA
Time frame: 12 months
Number of participants with adverse events
Time frame: 3 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2023.
- Individual participant dataSharing planned: No
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Sacituzumab Govitecan With Bevacizumab Compared to Usual Chemotherapy (Carboplatin, Pegylated Liposomal Doxorubicin and Bevacizumab) for Treating Recurrent Platinum-Sensitive Ovarian Cancer After PARP Inhibitor Maintenance Therapy
Recurrent Platinum-Sensitive Fallopian Tube Endometrioid Adenocarcinoma, Recurrent Platinum-Sensitive Fallopian Tube High Grade Serous Adenocarcinoma
RecruitingPhase 2
Testing Nivolumab With or Without Ipilimumab in Deficient Mismatch Repair System (dMMR) Recurrent Endometrial Carcinoma
Endometrial Adenocarcinoma, Endometrial Clear Cell Adenocarcinoma
RecruitingPhase 1/2
A Clinical Study of Raludotatug Deruxtecan in People With Ovarian Cancer (MK-5909-003).
Ovarian Cancer Recurrent
RecruitingPhase 3
A Clinical Trial of Raludotatug Deruxtecan (R-DXd) With or Without Bevacizumab in Participants With Ovarian Cancer Who Have Progressed During Treatment With PARP-inhibitors Treatment on First Line Maintenance (MK-5909-008/ENGOT-ov107/GOG-3142 / REJOICE-Ovarian05)
Ovarian Cancer, Peritoneal Cancer
Active, not recruitingPhase 2
Study of Senaparib in Combination With Temozolomide in ARID1A Mutation Associated Ovarian Cancer
Ovary Cancer, Fallopian Tube Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephanie Lheureux, M.D. principal investigator
Princess Margaret Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atezolizumab and Bevacizumab in people with Ovarian Endometrioid Tumor and Fallopian Tube Cancer, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants where increase in circulating deoxyribonucleic acid (ctDNA) level is related to progression (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2023.