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

NCT03283943 | Unknown Phase 1

• 1 other identifier: OZM-078
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Cancer; Primary Peritoneal Carcinoma; Fallopian Tube Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  First 4 weeks of therapy

Secondary Outcomes (3)

• Objective response rate

  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

  From date of study enrollment until confirmed CA-125 progression, through study completion, an average of 1 year

• Immune-related response rate

  From date of study enrollment until confirmed immune-related disease progression, through study completion, an average of one1year

Other Outcomes (1)

• Survival

  From date of study enrollment until death or study completion (maximum 12 months).

Study Arms (1)

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.

Radiation: Focal radiotherapy; Drug: Durvalumab

Interventions

Focal radiotherapy 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 and focal radiotherapy

Durvalumab DRUG

Durvalumab 1500 mg IV every 28 days

Also known as: MEDI 4736

Durvalumab and focal radiotherapy

Eligibility Criteria

• Age: 19 Years - 99 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• British Columbia Cancer Agency: lead
• Ozmosis Research Inc.: collaborator

Study Sites (1)

BC Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Central Study Contacts

Anna Tinker, MD

CONTACT

604-877-6000; atinker@bccancer.bc.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist

Study Record Dates

• First Submitted: June 30, 2017
• First Posted: September 15, 2017
• Study Start: April 1, 2018
• Primary Completion: December 16, 2020
• Study Completion: December 16, 2020
• Last Updated: July 11, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)