A clinical trial to check if combination therapy of osimertinib plus platinum plus pemetrexed is better than monotherapy (osimertinib) for patient with Epidermal growth factor receptor positive Locally Advance or Metastatic Non- small Cell Lung Cancer.
- Conditions
- Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
- Registration Number
- CTRI/2020/06/025980
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
1.Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
2.Provision of signed and dated, written informed consent form prior to any mandatory study-specific procedures, sampling, and analyses
3. For patients who agree to the optional genetic testing, provision of signed and dated genetic testing section of the written Main ICF prior to collection of a sample for genetic analysis for inclusion in the optional genetic research as allowed by local regulations
Age
4.Male or female, at least 18 years of age; patients from Japan at least 20 years of age
Type of patient and disease characteristics
5.Pathologically confirmed nonsquamous NSCLC
6.Newly diagnosed locally advanced (clinical stage IIIB, IIIC) or metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC (per Version 8 of the International Association for the Study of Lung Cancer [IASLC] Staging Manual in Thoracic Oncology), not amenable to curative surgery or radiotherapy
7. The tumor harbors 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations, which may include T790M, assessed by a CLIA-certified (US sites) or an accredited (outside of the US) local laboratory or by central prospective tissue testing
8.Mandatory provision of a baseline plasma sample and an unstained, archival tumor tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status
9. Patients must have untreated advanced NSCLC not amenable to curative surgery or radiotherapy. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapy, investigational agents, are permitted as long as treatment was completed at least 12 months prior to the development of recurrent disease
10.WHO PS of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks
11.Life expectancy >12 weeks at Day 1
12.At least 1 lesion, not previously irradiated that can be accurately measured at baseline as =10 mm in the longest diameter (except lymph nodes, which must have a short axis of =15 mm) with CT or MRI, and that is suitable for accurate repeated measurements. If only 1 measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and as long as it has not been biopsied within 14 days of the baseline tumor assessment scans
Reproduction
13.Female patients who are not abstinent (in line with the preferred and usual lifestyle choice of the patient) and intend to be sexually active with a male partner must be using highly effective contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to first dose of IP or must have evidence of non-child-bearing potential by fulfilling 1 of the following criteria at screening:
i. Post-menopausal, defined as more than 50 years of age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
ii. Women under 50 years old would be considered as postmenopausal if t
Medical conditions
1.Spinal cord compression; symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, and have a stable neurological status for at least 2 weeks after completion of the definitive therapy and steroids. Patients with asymptomatic brain metastases can be eligible for inclusion if in the opinion of the Investigator immediate definitive treatment is not indicated.
2.Past medical history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
3.Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
4.Any of the following cardiac criteria
i. Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine-derived QTcF value
ii. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG; eg, complete left bundle branch block, third-degree heart block, seconddegree heart block
iii. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities including serum/plasma potassium, magnesium and calcium below the LLN, heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes
correction of electrolyte abnormalities to within normal ranges can be performed during screening
5.Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
i. Absolute neutrophil count below the lower limit of normal (
ii. Platelet count below the LLN
iii. Hemoglobin <90 g/L
The use of granulocyte colony stimulating factor support, platelet transfusion and blood transfusions to meet these criteria is not permitted
iv. ALT >2.5 x the upper limit of normal (ULN) if no demonstrable liver metastases or >5 x ULN in the presence of liver metastases
v. AST >2.5 x ULN if no demonstrable liver metastases or >5 x ULN in the presence of liver metastases
vi. Total bilirubin >1.5 x ULN if no liver metastases or >3 x ULN in the presence of documented Gilberts Syndrome (unconjugated hyperbilirubinemia) or liver
vii. metastases
viii. Creatinine clearance <60 mL/min calculated by Cockcroft and Gault equation
6.Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of IP.
7.Any unresolved toxicities from prior systemic therapy (eg, adjuvant chemotherapy) greater than CTCAE Grade 1 at the time of starting study treatment, with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy.
8.Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would prec
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To evaluate the safety and tolerability of osimertinib <br/ ><br>plus chemotherapyTimepoint: RECIST 1.1 Evaluation- every 12 weeks from the 1st dose of IP. <br/ ><br> <br/ ><br>IDMC meeting at following timepoints <br/ ><br>60 patients across both treatment arm with at least 28 day of follow up. <br/ ><br>150 patients across both treatment arm with at least 28 day of follow up. <br/ ><br>300 patients across both treatment arm with at least 28 day of follow up. <br/ ><br> <br/ ><br>After completion of Recruitment <br/ ><br>Every 6 months until primary PFS analysis data cut off (278 progression events) <br/ ><br>
- Secondary Outcome Measures
Name Time Method