Cancer Molecular Screening and Therapeutics (MoST) Program Addendum 18 substudy 40: Durvalumab plus chemotherapy
- Conditions
- Extra-pulmonary small cell carcinomaCancer - Any cancer
- Registration Number
- ACTRN12621001225808
- Lead Sponsor
- The University of Sydney
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 6
1. Adults aged 18 years and older, with treatment-naïve histologically confirmed (immunohistochemistry positive for Cam5.2, and/ or TTF1, Chromogranin, synaptophysin, with or without CD56 positivity) extensive-stage extra-pulmonary small cell carcinoma, not amenable to curative radiotherapy or surgical resection.
2. All efforts should be made to ensure sufficient and accessible tissue, including both FFPE and fresh biopsy (<90 days old) for molecular screening, PD-L1 immunohistochemistry assay and exploratory objectives, unless deemed unsuitable by the study physician in discussion with the lead PI of this substudy. In which case archival tissue is acceptable. However, there is no need to wait for MTB report for participant to be enrolled and study treatment commenced.
3. ECOG performance status 0-1.
4. One cycle of platinum (either cisplatin or carboplatin) and etoposide for extensive-stage extrapulmonary small cell carcinoma is allowed, within 3 weeks of enrolment.
5. If the CNS is involved, this must be controlled/ stable either with local treatment or by steroids (maximum 10 mg daily prednisone or equivalent dose of an alternative corticosteroid).
6. Measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) without prior radiotherapy to these sites. If radiotherapy was given to a single target lesion, there must be clear radiological evidence of progression of the lesion since completion of the radiotherapy.
7. Adequate organ system function as assessed by the following minimal laboratory requirements (within 14 days prior to first administration of study drug):
a. Haemoglobin >= 9.0 g/L, Absolute neutrophil count (ANC) >=1.5 x 10^9/L), platelets >= 100 x 10^9/L,
b. Liver function; ALT/AST <= 2.5 x ULN (in the absence of liver metastases, <= 5 x ULN for patients with liver involvement) and total bilirubin <=1.5xULN (except participants with Gilbert’s Syndrome, who are eligible with bilirubin <=2.5 ULN)
c. Serum creatinine clearance >45 mL/min
8. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
9. Signed, written informed consent to participate in this specific treatment substudy.
10. Life expectancy of at least 12 weeks.
11. Body weight >30kg.
1. Prior systemic anti-cancer therapy for extensive-stage extrapulmonary small cell carcinoma, other than 1 cycle of platinum and etoposide given immediately prior to study registration.
2. Small cell transformation from other histology.
3. Large cell histology, including those of neuroendocrine origin, or small cell carcinoma of the ovary (hypercalcemic type).
4. Prior therapy with an anti-PD-1, anti-PD-L1 (including durvalumab), anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
5. Known history of hypersensitivity to active or inactive components or contraindications to durvalumab.
6. History of allergy or hypersensitivity to investigational product, cisplatin/ carboplatin, etoposide, or any excipient.
7. Participants with symptomatic or uncontrolled brain metastases or leptomeningeal disease are excluded.
8. 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.
e. Patients with celiac disease controlled by diet alone.
9. Any condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent dose of an alternative corticosteroid) or other immunosuppressive medications within 28 days of durvalumab administration. Intranasal, inhaled, or topical steroids or local steroid injections (e.g., intra-articular injection) are permitted in the absence of active autoimmune disease. Standard steroid premedication given prior to chemotherapy or as prophylaxis for imaging contrast allergy should not be counted for this criterion.
10. Current treatment or treatment within the last 12 months with any investigational anti-cancer products.
11. 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.
12. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 14 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.
13. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) >= 470 msec in screening ECG measured using standard institutional method or history of familial long QT syndrome.
14. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study treatment. Note: Local surgery of isolated lesions for palliative intent is acceptable.
15. No other malignancy that requires active treatment. Participants with a past history of adequately treated carcinoma in situ, non-melanoma skin cancer or lentigo maligna without evidence of disease or superficial transitional ce
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method