Brief Title
PDL-1 Inhibition and Focal Sensitizing Radiotherapy in Recurrent Ovarian/Primary Peritoneal/Fallopian Tube Cancers.
Official Title
Phase I (Safety Assessment) of Durvalumab (MEDI4736) With Focal Sensitizing Radiotherapy in Platinum Resistant Ovarian, Primary Peritoneal or Fallopian Tube Epithelial Carcinoma
Brief 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.
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 Phase
Phase 1
Study Type
Interventional
Primary Outcome
Determine the maximum tolerated dose of durvalumab combined with focal irradiation for use in recurrent ovarian cancer
Secondary Outcome
Objective response rate
Condition
Ovarian Cancer
Intervention
Focal radiotherapy
Study Arms / Comparison Groups
Durvalumab and focal radiotherapy
Description: Durvalumab 1500 mg IV every 28 days, and 2 fractions of focal sensitizing radiation with cycles 1 and 2 of treatment.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Radiation
Estimated Enrollment
22
Start Date
April 1, 2018
Completion Date
December 16, 2020
Primary Completion Date
December 16, 2020
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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
Exclusion Criteria:
- 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.
- 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.
Gender
Female
Ages
19 Years - 99 Years
Accepts Healthy Volunteers
No
Contacts
, 604-877-6000, [email protected]
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT03283943
Organization ID
OZM-078
Responsible Party
Principal Investigator
Study Sponsor
British Columbia Cancer Agency
Collaborators
Ozmosis Research Inc.
Study Sponsor
, ,
Verification Date
July 2018