A phase Ib study of Durvalumab (MEDI4736) in combination with carbon-ion radiotherapy and weekly cisplatin for patients with locally advanced cervical cancer

JRCT ID: jRCT2031210083

Registered date:12/05/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: cervical cancer
• Date of first enrollment: 10/12/2021
• Target sample size: 10
• Study type: Interventional
• Intervention(s): administration of durvalumab, carbon-ion radiotherapy and cisplatin according to the rules of the research protocol.

Outcome(s)

• Primary Outcome: AEs/SAEs including DLTs

Secondary Outcome

OS
Progression free survival
Distant metastasis rate at one year after treatment.
Objective response
Complete response rates.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 75age old
• Gender: Female

Include criteria

1. Age >= 20 years and <= 75 years for Japanese patients.
2. Histologically proven uterine cervical cancer; Stage IIB, IIIA, IIIB, IIIC1, and IVA in FIGO 2018 staging.
3. Tumor assessment by computed tomography scan or magnetic resonance imaging must be performed within 28 days prior to.
4. No prior chemotherapy, radiotherapy, or immunotherapy for cervical cancer.
5. ECOG performance status of 0 or 1.
6. Body weight > 30 kg
7. Adequate normal organ and marrow function as defined below:
Haemoglobin >= 9.0 g/dL
Absolute neutrophil count >= 1000 per mm3
Platelet count >= 75 x 109/L
Serum bilirubin <= 1.5 x institutional upper limit of normal.
8. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
9. Must have a life expectancy of at least 12 weeks.
10. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.

Exclude criteria

1) Participation in another clinical study with an investigational product during the last 3 months.
2) Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
3) Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) for other previous or concomitant tumor within 1 years prior to the first dose of study drug.
4) Any unresolved toxicity NCI CTCAE Grade >=2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
a. Patients with Grade <= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
b. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
5) Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
6) Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
7) Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
8) History of allogenic organ transplantation.
9) Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
a. Patients with vitiligo or alopecia
b. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
c. Any chronic skin condition that does not require systemic therapy
d. Patients without active disease in the last 5 years may be included but only after consultation with the study physician
e. Patients with celiac disease controlled by diet alone
10) Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
11) History of another primary malignancy except for
a. Malignancy treated with curative intent and with no known active disease >=5 years before the first dose of IP and of low potential risk for recurrence
b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
c. Adequately treated carcinoma in situ without evidence of disease
12) History of leptomeningeal carcinomatosis
13) History of active primary immunodeficiency
14) Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
15) Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
a. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
b. Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent
c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
16) Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
17) Female patients who are pregnant or breastfeeding or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
18) Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
19) Prior randomisation or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
20) Patients who have received prior anti PD-1, anti PD-L1including durvalumab or anti CTLA-4.
21) Resectable uterine cervical cancer.
22) Recurrence of uterine cervical cancer.
23) Patients with intestinal invasion of cervical cancer.
24) Uncontrollable pain due to cervical cancer.
25) Patients who have active or history of severe interstitial pneumonia or pulmonary fibrosis.
26) Patients with ileus.
27) Patients with systemic infection which required intensive treatment.
28) Patients with a history of transient ischemic stroke, cerebrovascular accident, thrombosis, or thromboembolism within 180 days before the enrolment of this study.
29) Patients with uncontrolled diabetes or bleeding tendency.
30) Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.
31) Judged to be ineligible as a result of screening tests and related medical examinations at Chiba University Hospital.
32) Determined to be ineligible by the physician in charge for any other reason

Related Information

• Primary Sponsor: Murata Kazutoshi
• Source(s) of Monetary Support: Astrazeneca Co., Ltd.