A Phase 2 Study of Osimertinib in combination with Platinum-pemetrexed in patients with EGFR-mutated Advanced non-small cell Lung cancer.

JRCT ID: jRCTs031180226

Registered date:11/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Non-squamous non-small cell lung cancer
• Date of first enrollment: 11/03/2019
• Target sample size: 66
• Study type: Interventional
• Intervention(s): Oshimertinib 80mg/day with cisplatin 75mg/m2 or carboplatin AUC 5plus pemetrexed 500mg/m2 every3week are administred up to 4cycles,followed by osimertinib 80mg/day and pemetrexed 500mg/m2 every 3week till the discontinuation criteria such as progression(PD).

Outcome(s)

• Primary Outcome: Safety (Adverse events graded by CTCAE version 5.0), ORR according to RECIST version 1.1)
• Secondary Outcome: Complete response rate, disease control rate, progression-free survival (All according to RECIST v1.1)

Key inclusion & exclusion criteria

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

Include criteria

1 .Patients with a diagnosis of non-squamous non-small cell lung cancer (NSCLC) histologically or cytologically.
2.Patients that are in stage IIIb, IIIc or stage IVa,IVb, (UICC 8th version) or have recurrence postoperatively without indication for surgical or radical radiation therapy.
3. The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations.
4.Patients with measurable lesions that can be evaluated by RECIST (version1.1)
5. Chemotherapy-naive and EGFR-TKI- naive and immune-checkpoint inhibitor- naive patients
* Prior adjuvant and neo-adjuvant therapies except for EGFR inhibitors are permitted as long as treatment was completed at least 6 months prior to the development of recurrent disease
6. From 20 to 75 years of age
7. PS 0 or 1 (ECOG)
8.Normal main organ functions (in principle, they should have the following values.)
1)Absolute neutrophil count >= Lower limit of normal (LLN)
2)Hemoglobin >= 9.0g/dL
3)Platelet count >= Lower limit of normal (LLN)
4)AST <= 2.5 times ULN if no demonstrable liver metastases or <= 5 times ULN in the presence of liver metastases
5)ALT <= 2.5 times ULN if no demonstrable liver metastases or <= 5 times ULN in the presence of liver metastases
6)Total bilirubin <= 1.5 times ULN if no liver metastases or <= 3 times ULN in the presence of documented Gilberts Syndrome or liver metastases
7)Creatinine clearance >= 50ml/min (calculated value)
8)SpO2 >= 95 %
9)LVEF >= 55 %
9. Written informed consent must be given

Exclude criteria

(1) Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
(2) Patients with clinically unstable brain metastases or spinal cord compression (However, patients are eligible if they are not on steroids, and have had a stable neurological status for at least 2 weeks after completion of definitive therapy and steroids.)
(3) Patients that have received radiation therapy for primary lesions (While, two weeks after a treatment with radiation for brain and/or bone metastasis, the patient can be enrolled.)
(4) Patients with severe complications such as uncontrolled heart, lung, liver, or kidney disease or diabetes mellitus.
(5) Any of the following cardiac criteria:
1) Mean resting corrected QT interval (QTc) > 470 msec
2) Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block.
3) Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities including :
1. Serum/plasma potassium <lower limit of normal(LLN)
2. Serum/plasma magnesium <lower limit of normal (LLN)
3. Serum/plasma calcium <lower limit of normal (LLN)
4. Heart failure, hypokalaemia, 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 pointe
(6) Any evidence of active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
(7) Male patients without an intention to use the measures of contraception. Or pregnant women, lactating women, women who are positive for pregnancy tests or women without an intention to use the measures of contraception*.
*However, the following female patients can be enrolled;
1. Female patient aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
2. Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution.
3. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salping ectomy but not tubal ligation.
(8) Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, total gastrectomy or previous significant bowel resection that would preclude adequate absorption of osimertinib
(9) Patients with pleural effusion, pericardial effusion and/or peritoneal effusion requiring tube drainage (While, if a patient has been clinically stable after drainage, the patient can be enrolled.)
(10) Besides the above-mentioned cases, those with contraindications for therapy with osimertinib, cisplatin, carboplatin, pemetrexed.
(11) Patients with active double cancers other than intramucosal carcinoma
(12) Patients who are not capable of oral ingestion
(13) Patients have a life expectancy <= 12 weeks
(14) Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
(15) Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater
(16) Currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 week prior)
(17) Patients with known hypersensitivity to any of the active or inactive excipients of study drugs (osimertinib, cisplatin, carboplatin and pemetrexed) or related compounds.
(18) Any evidence of 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 jeopardise compliance with the protocol
(19) Other cases that are determined to be inappropriate by attending physicians.

Related Information

• Primary Sponsor: Kobayashi Kunihiko
• Secondary Sponsor: Nonprofit Organization, North East Japan Study Group