Phase 1b study of safety and tolerability in patients treated with stereotactic radiotherapy combined with durvalumab and tremelimumab in stage 4 NSCLC
- Conditions
- Non-small cell lung cancer (NSCLC)10038666
- Registration Number
- NL-OMON44296
- Lead Sponsor
- niversitair Medisch Centrum Groningen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 25
- Written informed consent;
- Histologically confirmed stage IIIB (without curative treatment options) and stage IV NSCLC. Tumor mutation status must be known, analyzed by next generation sequencing for specific mutations;
- A tumour tissue sample (< 6 month old);
- Any line of previous chemotherapy (but at least 1 line), with washout period of at least 4 weeks;
- At least one unidimensionally measurable lesion according to RECIST1.1 criteria;
- Age * 18 years;
- ECOG / WHO performance status of 0 or 1;
- Life expectancy of *12 weeks;
- Body weight > 30 kg;
- Adequate normal organ and bone marrow function:
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.
- Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women * 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >;1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- Subject is willing and able to comply with the protocol for the duration of the study;
- Male and female patients with reproductive potential must use an approved contraceptive method, if appropriate. Female patients with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
- Involvement in the planning and/or conduct of the study
- Participation in another clinical study with an investigational product during the last 3 months.
- 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.
- Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) 1 month prior to the first dose of study drug (wash out period).
- Primary tumor smaller than 3 cm.
- 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.
- Patients with Grade * 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.
- Any history of radiotherapy treatment to the chest.
- Any prior radiotherapy (including palliative radiotherapy to non-target lesions) within 4 month of the first dose of study drug.
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
- History of leptomeningeal carcinomatosis
- Subjects with untreated CNS metastases are excluded.
- Active or prior documented autoimmune or inflammatory disorders
- Uncontrolled intercurrent illness
- Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
- History of allogenic organ transplantation.
- History of active primary immunodeficiency
- Active infection including tuberculosis, hepatitis B, hepatitis C, or HIV. Patients with a past or resolved HBV infection and absence are eligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for HCV RNA
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab
- 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
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
- Patients who have received any prior anti-PD-1, anti PD-L1 or anti CTLA-4.
- Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
- Judgment by the investigator that the patient is unsuitable to participate in the study
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Establishing MTD in 3 sequential combination immunotherapy * radiotherapy<br /><br>cohorts. Percentage of grade III/IV toxicities determined between first<br /><br>radiotherapy day and 8 weeks after combination treatment.</p><br>
- Secondary Outcome Measures
Name Time Method <p>All AEs, PFS, OS, response rate, T cell immune response (intracellular<br /><br>production of IL-2, IFN-*, TNF-* and IL-4 by CD4+ en CD8+ T cells to 6<br /><br>different stimuli).</p><br>