Randomized phase III study of erlotinib + bevacizumab vs erlotinib

JRCT ID: jRCTs031180056

Registered date:19/12/2018

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Advanced non-squamous non-small cell lung cancer
• Date of first enrollment: 03/06/2015
• Target sample size: 214
• Study type: Interventional

Intervention(s)

The erlotinib plus bevacizumab arm.
Erlotinib 150 mg/day will be taken orally at one hour before daily breakfast starting from day 1 of cycle 1. Bevacizumab 15 mg/kg will be administered as an intravenous infusion on day 1 of every 21-day (+ 3days) cycle. Patients will be remained on treatment until disease progression or unacceptable toxicity, as per the protocol. If either drug will be discontinued, the other can be continued on a 21-day cycle.

The erlotinib monotherapy arm.
Erlotinib 150 mg/day will be taken orally at one hour before daily breakfast starting from day 1 of cycle 1. Patients will be remained on treatment until disease progression or unacceptable toxicity, as per the protocol. If erlotinib administration will be suspended into next cycle, the resumed day is regarded as day 1 of next cycle.

Outcome(s)

• Primary Outcome: Progression-free survival
• Secondary Outcome: Overall survival, response rate, disease control rate, duration of response, safety, QOL

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1)Histologically or cytologically documented non-squamous NSCLC
(2)EGFR (Exon 19 deletion or Exon 21 L858R) mutation status, detected with PCR, is active
(3)Stage IIIB or stage IV or recurrent NSCLC
(4)No prior systemic chemotherapy. Patients with history of treatment with anticancer drugs for pleurodesis are not eligible. If patients have received neoadjuvant / adjuvant chemotherapy, the patients who experience recurrence after 6 months are permitted
(5)Regarding the patients who have be treated withradiotherapy;
1)Not have received radiotherapy to lesions of lung
2)More than 2 weeks after receiving radiotherapy to lesions except lung
(6)Regarding the patients who have be treated with therapy as follows;
1)More than 4 weeks after the last operation
2)More than 2 weeks after the last pleurodesis except anticancer drugs
3)More than 2 weeks after the last biopsy with an incision
4)More than 2 weeks after the last treatment for injury
5)More than 2 weeks after the last blood transfusion
6)More than 4 weeks after the last administration of other investigational drugs
(7)Patients who have at least one or more measurable lesion by RESIST (Version1.1)
(8)Aged >=20, at the time of consent
(9)ECOG PS 0-2
(10)Have adequate organ function as follows;
1)neutrophil >=1,500/mm3
2)hemoglobin >=9.0g/dL
3)platelet >=100,000/mm3
4)bilirubin <=1.5mg/dL
5)AST/ALT <=2.5xULN
6)serum creatinine <=1.5mg/dL
7)PaO2(room air) >=70Torr or SpO2 >=94%
8)APTT <=ULN
9)PT-INR <=1.5
10)urine protein under 1+
(11)Written informed consent
(12)Estimated life expectancy at least 3 months

Exclude criteria

(1)Exon 20 T790M mutation status, detected with PCR, is active. Have received
(2)Have symptomatic brain metastasis
(3)Have a history of multiple malignancies within 5 years
(4)History of pulmonary hemorrhage or hemoptysis as defined below;
1)Hemosputum continuing for more than 1 week within 1 year before enrollment.
2)Have had or require continuous oral administration of hemostat
3)Have had or require injectable administration of hemostat
(5)Evidence of bleeding diathesis or hemoptysis
(6)Evidence of tumor invading a perihilar blood vessel or cavitation in intra-thoracic lesion on imaging
(7)Evidence of tumor invading segmental bronchus
(8)Uncontrolled pleural, ascites effusion or cardiac effusion
(9)Having a history or serious complications as bellows;
1)SVC syndrome complication
2)Spinal cord compression
3)Having a history of serious symptomatic cerebrovascular disease within 1 year before enrollment
4)Unrecovered fracture or severe injury
5)Systemic treatment of steroid for more than 4 weeks
6)Have severe infection
7)Having a history or evidence of ILD complication on imaging or lung infection (except history of radiation pneumonitis in radiation area)
8)Have gastrointestinal dysfunction as follows;
<1>Impossible to take drugs orally
<2>Need intravenous feeding
<3>Have malabsorption by surgery
<4>Have active peptic ulcer
9)Have severe corneal disease complication
10)Have severe heart disease complication
11)Have diverticulitis
12)Have ever had a history of gastrointestinal perforation within 1 year prior to registration
13)Have severe neurological deficit or mental disorder
14)Have active hepatic disease
(10)Surgery planned in trial period
(11)Have a history of severe allergy of other monoclonal antibody drugs
(12)Have a history of EGFR TKI or anti-angiogenesis drug administration
(13)Pregnant or breast-feeding woman
(14)Patients who have no will to contraception
(15)Patients whose participation in the trial is judged to be inappropriate by the doctor

Related Information

• Primary Sponsor: Maemondo Makoto
• Secondary Sponsor: Nonprofit Organization, North East Japan Study Group,Nonprofit Organization, North East Japan Study Group
• Secondary ID(s): UMIN000017069