Ovarian CancerPhase 1NCT03283943
PDL-1 Inhibition and Focal Sensitizing Radiotherapy in Recurrent Ovarian/Primary Peritoneal/Fallopian Tube Cancers.
A Phase 1 study testing Focal radiotherapy and Durvalumab in people with Ovarian Cancer and Primary Peritoneal Carcinoma, run by British Columbia Cancer Agency at 1 site in Canada.
Trial summary
It is postulated that focal sensitizing radiotherapy may potentiate the effectiveness of durvalumab. The purpose of this study is to test the safety and tolerability of 2 different dose levels of focal sensitizing radiation therapy given with durvalumab. Read more about this study
- Who is it for?
- Ages 19 to 99 years, women only
- Conditions the study is for
- Ovarian Cancer, Primary Peritoneal Carcinoma, Fallopian Tube Cancer
- What is being tested?
- Focal radiotherapy and Durvalumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteCanada
- Study dates
- 1 Apr 2018to 16 Dec 2020
- Phase
- Phase 1
- 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 19 to 99 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of written informed consent prior to any study specific procedures
- Female patients aged 19 years and older
- Platinum-resistant (progression within 6 months of platinum based regimen) or platinum-refractory ovarian/fallopian tube/peritoneal origin.
- High grade serous, endometrioid, clear cell, mucinous, malignant mixed Mullerian tumor, and low grade serous histotypes are permitted. Non-epithelial tumours will not be permitted.
- ECOG performance status 0-1.
- No more than 2 lines of therapy in the platinum-resistant setting.
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- No bowel obstructions within the preceding 6 months.
- Last radiation therapy treatment ≥3 months prior to enrollment.
- Expected survival >3 months.
- All patients much have at least one site of measurable disease as defined by RECIST criteria (v.1.1).
- All patients must have disease suitable for core biopsy and agree to study related biopsies. Disease suitable for biopsy can serve as radiation targets, but cannot be used for response assessment.
- All patients must have at least 2 additional sites of disease that serve are suitable radiation targets (see section 6.2.1).
- Lesions suitable for radiation targeting must meet all of the following criteria:
- each target must be > 4 cc in volume by standard imaging techniques, such as CT scan, MRI, or radiograph
- for each lesion, partial treatment of a tumour mass is permitted, but the treatment volume cannot be less than the equivalent of a 2cm sphere (4cc) and the two targets cannot be part of the same contiguous mass
- must be outside of previously irradiated fields 12. Adequate organ and marrow function
Who cannot join
- Subjects who cannot meet all the radiation planning constraints will not be eligible for this trial.
- Participation in another clinical study with an investigational agent during the last 4 weeks.
- Concurrent enrolment in another clinical study, the only exception being observational (non-interventional) clinical studies.
- History of pneumonitis requiring treatment with steroids, or has a history of interstitial lung disease.
- Patients who have contraindications to receiving radiation therapy, such as: Rheumatoid Arthritis, connective tissue disorders, Lupus, scleroderma, CREST syndrome, Crohn's syndrome, Ulcerative colitis, or other conditions identified by the Radiation Oncologist as unsuitable for radiation therapy.
- Current or prior use of immunosuppressive medication within 28 days before the first dose of the study drug, with the exception of intra-nasal and inhaled corticosteroids or systemic corticosteroids at physiologic doses, which must not exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
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- Prior exposure to an anti-PD-1 or anti-PD-L1 antibody.(including durvalumab
- History of acute diverticulitis, intra-abdominal abscess, or GI obstruction.
- Previous severe hypersensitivity reaction to another monoclonal antibody (mAb).
- Active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Patients with Vitiligo, Grave's disease or psoriasis not requiring systemic treatment (within the past 2 years) or those with resolved childhood asthma/atopy are not excluded.
- Uncontrolled intercurrent illness including: infection requiring therapy, symptomatic congestive heart failure, uncontrolled hypertension (systolic blood pressure > 150 and diastolic blood pressure >100), unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses.
- Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from using Frediricia'sCorrection.
- Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface Antigen [HBsAg] reactive), or Hepatitis C virus (Hepatitis C Virus Ribonucleic Acid [HCV RNA] (qualitative) is detected).
- Previous clinical diagnosis of active tuberculosis.
- Receipt of a live attenuated vaccination within 30 days of study entry or within 30 days or receiving the study drug.
- History of another malignancy, with the exception of:
- Malignancy treated with curative intent without evidence of recurrence for ≥ 5 years
- Adequately treated non -melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease e.g. cervical carcinoma in situ
- Female patients who are pregnant, breast-feeding or of childbearing potential who are not employing an effective method of birth control (see Table 3).
- Any condition that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of patient safety or study.
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
BC Cancer Agency
Vancouver, British Columbia, V5Z 4E6
Anna Tinker, MD, 6048776000, atinker@bccancer.bc.ca
About this study
Official title: Phase I (Safety Assessment) of Durvalumab (MEDI4736) With Focal Sensitizing Radiotherapy in Platinum Resistant Ovarian, Primary Peritoneal or Fallopian Tube Epithelial Carcinoma
It is postulated that focal sensitizing radiotherapy may potentiate the effectiveness of durvalumab. The purpose of this study is to test the safety and tolerability of 2 different dose levels of focal sensitizing radiation therapy given with durvalumab.
Read the detailed description
Durvalumab is a PDL-1 inhibitor, part of class of agents (called checkpoint inhibitors) designed to increase the ability of the immune system to recognize and work to eliminate cancers. Checkpoint inhibitors have been studied in recurrent ovarian, primary peritoneal and Fallopian cancers, and on their own show a low level of activity.
Radiation therapy is usually used in women with recurrent ovarian, primary peritoneal and Fallopian cancers to palliate symptoms related to progressive disease. However, radiation is know to modify the cancer immune environment and to release tumour antigens. These actions may potentiate the function of immune checkpoint inhibitors.
- Being tested
- Focal radiotherapy, Durvalumab
- Medical subject headings
- Ovarian Neoplasms, Fallopian Tube Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Focal radiotherapyRadiation
Focal sensitizing radiotherapy will be given at a starting dose level of 24 Gray (6 Gy X 4 fractions), and may be escalated to 32 Gy (8Gy X4 fractions).
DurvalumabDrug
Also called MEDI 4736
Durvalumab 1500 mg IV every 28 days
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab and focal radiotherapy | Experimental | Durvalumab 1500 mg IV every 28 days, and 2 fractions of focal sensitizing radiation with cycles 1 and 2 of treatment. Receives: Radiation: Focal radiotherapy; Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the maximum tolerated dose of durvalumab combined with focal irradiation for use in recurrent ovarian cancer
The maximum tolerated dose will be defined by dose-limiting toxicities and serious adverse events.
Measured: First 4 weeks of therapy
Secondary outcomes (3)
Objective response rate
Objective Response rate as evaluated by RECIST (v 1.1) criteria 2) Progression free survival 3) Overall survival
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
CA-125 response rate
Using GCIG CA-125 response criteria
Measured: From date of study enrollment until confirmed CA-125 progression, through study completion, an average of 1 year
Immune-related response rate
Using Immune-related response criteria
Measured: From date of study enrollment until confirmed immune-related disease progression, through study completion, an average of one1year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2017
- Study start1 Apr 2018
- Primary completion16 Dec 2020 (estimated)
- Study completion16 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by British Columbia Cancer AgencyThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- British Columbia Cancer Agency
- Sponsor type
- University, hospital or other
- Collaborators
- Ozmosis Research Inc.
- Responsible party
- Principal investigator, Anna Tinker, British Columbia Cancer Agency
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03283943
- Sponsor's protocol ID
- OZM-078
- Status last verified
- Jul 2018
- First submitted
- 30 Jun 2017
- Last updated
- 11 Jul 2018
- Results posted
- No
- 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 11 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I (Safety Assessment) of Durvalumab (MEDI4736) With Focal Sensitizing Radiotherapy in Platinum Resistant Ovarian, Primary Peritoneal or Fallopian Tube Epithelial Carcinoma
- ClinicalTrials.gov ID
- NCT03283943
- Acronym / sponsor ID
- OZM-078
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- British Columbia Cancer AgencyUniversity, hospital or other
- Collaborators
- Ozmosis Research Inc.
- Study start
- 1 Apr 2018 (actual)
- Primary completion
- 16 Dec 2020 (estimated)
- Study completion
- 16 Dec 2020 (estimated)
- First posted
- 15 Sep 2017 (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.
It is postulated that focal sensitizing radiotherapy may potentiate the effectiveness of durvalumab. The purpose of this study is to test the safety and tolerability of 2 different dose levels of focal sensitizing radiation therapy given with durvalumab.
Detailed description
Durvalumab is a PDL-1 inhibitor, part of class of agents (called checkpoint inhibitors) designed to increase the ability of the immune system to recognize and work to eliminate cancers. Checkpoint inhibitors have been studied in recurrent ovarian, primary peritoneal and Fallopian cancers, and on their own show a low level of activity.
Radiation therapy is usually used in women with recurrent ovarian, primary peritoneal and Fallopian cancers to palliate symptoms related to progressive disease. However, radiation is know to modify the cancer immune environment and to release tumour antigens. These actions may potentiate the function of immune checkpoint inhibitors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Durvalumab and focal radiotherapy | Experimental | Radiation: Focal radiotherapy, Drug: DurvalumabDurvalumab 1500 mg IV every 28 days, and 2 fractions of focal sensitizing radiation with cycles 1 and 2 of treatment. |
Who may qualify
- Ages
- 19 to 99 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Provision of written informed consent prior to any study specific procedures
- Female patients aged 19 years and older
- Platinum-resistant (progression within 6 months of platinum based regimen) or platinum-refractory ovarian/fallopian tube/peritoneal origin.
- High grade serous, endometrioid, clear cell, mucinous, malignant mixed Mullerian tumor, and low grade serous histotypes are permitted. Non-epithelial tumours will not be permitted.
- ECOG performance status 0-1.
Key exclusion criteria (21 listed)
- Subjects who cannot meet all the radiation planning constraints will not be eligible for this trial.
- Participation in another clinical study with an investigational agent during the last 4 weeks.
- Concurrent enrolment in another clinical study, the only exception being observational (non-interventional) clinical studies.
- History of pneumonitis requiring treatment with steroids, or has a history of interstitial lung disease.
- Patients who have contraindications to receiving radiation therapy, such as: Rheumatoid Arthritis, connective tissue disorders, Lupus, scleroderma, CREST syndrome, Crohn's syndrome, Ulcerative colitis, or other conditions identified by the Radiation Oncologist as unsuitable for radiation therapy.
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 |
|---|---|---|
| Focal radiotherapyFocal sensitizing radiotherapy will be given at a starting dose level of 24 Gray (6 Gy X 4 fractions), and may be escalated to 32 Gy (8Gy X4 fractions). | Radiation | Durvalumab and focal radiotherapy |
| DurvalumabAlso: MEDI 4736Durvalumab 1500 mg IV every 28 days | Drug | Durvalumab and focal radiotherapy |
Primary outcome
Determine the maximum tolerated dose of durvalumab combined with focal irradiation for use in recurrent ovarian cancer
Time frame: First 4 weeks of therapy
The maximum tolerated dose will be defined by dose-limiting toxicities and serious adverse events.
3 secondary outcomes
Objective response rate
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
CA-125 response rate
Time frame: From date of study enrollment until confirmed CA-125 progression, through study completion, an average of 1 year
Immune-related response rate
Time frame: From date of study enrollment until confirmed immune-related disease progression, through study completion, an average of one1year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2018.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Focal radiotherapy and Durvalumab in people with Ovarian Cancer and Primary Peritoneal Carcinoma, run by British Columbia Cancer Agency 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 16 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 11 Jul 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anna Tinker, MD (604-877-6000, atinker@bccancer.bc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the maximum tolerated dose of durvalumab combined with focal irradiation for use in recurrent ovarian cancer (time frame: First 4 weeks of therapy). 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 11 Jul 2018.