A Phase Ib, Open-label, Single-center study to assess the safety of cancer-immunotherapy induction with Tremelimumab and Durvalumab prior to Chemoradiotherapy and/or Resection in the treatment of locally advanced NSCLC.
- Conditions
- Non-Small Cell Lung CancerLung Cancer10038666
- Registration Number
- NL-OMON55743
- Lead Sponsor
- Antoni van Leeuwenhoek Ziekenhuis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 34
1. Provision of signed, written and dated informed consent prior to any study
specific procedures.
2. Male or female aged 18 years or older.
3. WHO performance status of 0 or 1.
4. Pathologically proven NSCLC stage III or inoperable stage II (cT1-3N0-1),
according to the 8th edition of the AJCC staging, with a clinical indication
for concurrent chemo-irradiation.
5. Body weight >30kg
6. Patients with locoregional recurrent lung tumour following surgery or a
second primary cancer are eligible, unless a pneumonectomy was performed.
7. Negative pregnancy test (urine or serum) for female patients with
childbearing potential;
8. For women of childbearing potential: agreement to remain abstinent (refrain
from heterosexual intercourse) or use contraceptive methods that result in a
failure rate of <= 1% per year, during the treatment period and for at least 180
days after the last dose of Durvalumab and Tremelimumab combination therapy or
1 month after the last dose of chemotherapy, whichever is later.
A woman is considered to be of childbearing potential if she is postmenarcheal,
has not reached a postmenopausal state (>=12 continuous months of amenorrhea
with no identified cause other than menopause), and has not undergone surgical
sterilization (removal of ovaries and/or uterus).
Examples of contraceptive methods with a failure rate of <= 1% per year include
bilateral tubal ligation, male sterilization, established proper use of
hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine
devices (IUDs), and copper IUDs.
The following age-specific requirements apply:
- 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).
9. Adequate organ function. Minimum required laboratory data: see protocol
10. All acute toxic effects of any prior radiotherapy, chemotherapy, or
surgical procedure must have resolved to Grade <= 1, except alopecia (any
grade). Patients with Grade >=2 neuropathy will be evaluated on a case-by-case
basis after consultation with the Study Physician.
11. Patients should be medically operably defined by:
a. Sufficient cardiopulmonary function (Brunelli, Kim, Berger, &
Addrizzo-Harris, 2013)
b. No major contra-indications for surgery.
Exclusion Criteria A potential subject who meets any of the following criteria
will be excluded from participation in this study:
1. Patients with grade 3 dyspnoea or worse at baseline (according to CTCAE
version 4.03).
2. Prior radiotherapy to the thorax.
3. Participation in another clinical study with an investigational product
during the last 4 weeks.
4. Concurrent enrolment in another clinical study, unless it is an
observational (non-interventional) clinical study or the follow-up period of an
interventional study.
5. Recent major surgery within 4 weeks prior to entry into the study (excluding
the placement of vascular access) that would prevent administration of
chemotherapy.
6. 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., Exclusion Criteria 7.
Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow*up
schedule; those conditions should be discussed with the patient before
registration in the trial.
8. Any condition that, in the opinion of the investigator, would interfere with
evaluation of the CRT or interpretation of patient safety or study results.
9. 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.
10. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, 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 (eg, 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
11. Subject noncompliance that, in the opinion of the investigator or sponsor,
warrants withdrawal; eg, refusal to adhere to scheduled visits
12. General contra-indications for immunotherapy:
a. 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, or human immunodeficiency virus (positive
HIV 1/2 antibodies). 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. Pat
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is safety. Treatment is deemed safe if adverse events can<br /><br>be managed and patients have completed the planned multimodality treatment,<br /><br>defined by CIT-CRT/R. </p><br>
- Secondary Outcome Measures
Name Time Method