PDL-1 Inhibition and Focal Sensitizing Radiotherapy in Recurrent Ovarian/Primary Peritoneal/Fallopian Tube Cancers.

NCT ID: NCT03283943

Last Updated: 2018-07-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-01
• Study Completion Date: 2020-12-16

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.

Conditions

Ovarian Cancer; Primary Peritoneal Carcinoma; Fallopian Tube Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Durvalumab and focal radiotherapy

Durvalumab 1500 mg IV every 28 days, and 2 fractions of focal sensitizing radiation with cycles 1 and 2 of treatment.

Group Type: EXPERIMENTAL

Focal radiotherapy

Intervention Type: RADIATION

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).

Durvalumab

Intervention Type: DRUG

Durvalumab 1500 mg IV every 28 days

Interventions

Focal radiotherapy

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).

Intervention Type: RADIATION

Durvalumab

Durvalumab 1500 mg IV every 28 days

Intervention Type: DRUG

Other Intervention Names

MEDI 4736

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.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ozmosis Research Inc.

INDUSTRY

Sponsor Role: collaborator

British Columbia Cancer Agency

OTHER

Sponsor Role: lead

Responsible Party

Anna Tinker

Medical Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

BC Cancer Agency

Vancouver, British Columbia, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Anna Tinker, MD

Role: CONTACT

atinker@bccancer.bc.ca

604-877-6000

Facility Contacts

Anna Tinker, MD

Role: primary

atinker@bccancer.bc.ca

6048776000

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

OZM-078

Identifier Type: -

Identifier Source: org_study_id