TELMA: Atezolizumab Plus Bevacizumab in First Line NSCLC Patients

Sponsor

Fundación GECP (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03836066

Collaborator

(none)

Enrollment

Locations

Arm

56.5

Anticipated Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multi-center phase II clinical trial of atezolizumab in combination with bevacizumab as first line treatment for locally advanced or metastasic high-intermediate tumour mutation burden selected NSCLC patients. 102 patients will be enrolled in this trial to examine the efficacy of this combination measured by progression free survival according to response evaluation Criteria in solid tumours (RECIST) version 1.1.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: Atezolizumab-Bevacizumab	Phase 2

Detailed Description

Chemotherapy-naïve patients high-intermediate TMB (TMB≥10 mutations/MB) and with locally advanced or metastatic non-squamous non-small cell lung cancer patients will be selected. Enroled patientswill receive 1200 mg of atezolizumab and 15mg/Kg of Avastin® (bevacizumab) administered by IV infusion every 21 days (+/- 3 days).

The treatment will start within 1-5 days from enrolment. Atezolizumab may continue beyond disease progression per RECIST v1.1 until loss of clinical benefit, unacceptable toxicity, patient or physician decision to discontinue , or death. Bevacizumab will be administered until progression disease, unacceptable toxicity, patient or physician decision to discontinue or death.

For all patients, tumour response data collection will continue until disease progression, even if the patient stops study treatment prior to disease progression.

The primary endpoint is to evaluate the efficacy of Atezolizumab in combination with Bevacizumab as measured by Progression Free Survival according to RECIST Version 1.1.

PFS after enrolment is defined as the time from enrolment to the first occurrence of disease progression or death from any cause, whichever occurs first.

Patient accrual is expected to be completed within 1.5 years excluding a run-in-period of 46 months. Treatment and follow-up are expected to extend the study duration to a total of 4.5 years. Patients will be followed 1.5 years after the end of treatment independently of the cause of end of treatment. The study will end once survival follow-up has concluded.

Study Design

Study Type:

Interventional

Actual Enrollment :

41 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Open Label Study of Atezolizumab in Combination With Bevacizumab as First Line Treatment for Locally Advanced or Metastasic High-intermediate Tumor Mutation Burden Selected Non-squamous Non-small Cell Lung Cancer Patients.

Actual Study Start Date :

May 15, 2019

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Jan 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental: Atezolizumab plus Bevacizumab arm 1 group, Atezolizumab 1200mb + Bevacizumab 15 mg/kg (IV),every 21 days.	Drug: Atezolizumab-Bevacizumab Atezoluzumab 1200 mg + Bevacizumab 15 mg / kg Other Names: Tecentriq-Avastin

Arm

Intervention/Treatment

Experimental: Experimental: Atezolizumab plus Bevacizumab arm

1 group, Atezolizumab 1200mb + Bevacizumab 15 mg/kg (IV),every 21 days.

Drug: Atezolizumab-Bevacizumab

Atezoluzumab 1200 mg + Bevacizumab 15 mg / kg

Other Names:

Tecentriq-Avastin

Outcome Measures

Primary Outcome Measures

Efficacy of Atezolizumab in combination with Bevacizumab [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months]
To evaluate the efficacy of Atezolizumab in combination with Bevacizumab as measured by Progression Free Survival according to Response Evaluation Criteria in Solid Tumours (RECIST).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female, aged ≥ 18 years old
ECOG performance status of 0 or 1.
Histologically or cytologically confirmed, Stage IIIB or IV non-squamous NSCLC according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology
No prior treatment for Stage IIIB or IV non-squamous NSCLC.
Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemo-radiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemo-radiotherapy.
Patients with a treated asymptomatic CNS metastasis are eligible, provided they meet all of the following criteria:
Only supratentorial and cerebellar metastases allowed (i.e., no metastases to midbrain, pons, medulla or spinal cord).
No ongoing requirement for corticosteroids as therapy for CNS disease.
No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization.
No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study. Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible without the need for an additional brain scan prior to inclusion, if all other criteria are met.
Patients with high-intermediate Tumour Mutational Burden analysed by Foundation Medicine (≥10 mutations/ MB) performed by a Foundation Medicine laboratory on previously obtained archival tumour tissue or tissue obtained from a biopsy at prescreening (sample must fulfil minimal sample requirements of 20% tumour cellularity and a minimum surface of 25mm2).
Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site since radiation and the previously irradiated lesion is not the only site of disease.
Adequate hematologic and organ function defined by the following laboratory results obtained within 14 days prior to randomization:

Neutrophils ≥ 1500 cells/μL without granulocyte colony-stimulating factor support.

Lymphocyte count ≥ 500/μL.
Platelet count ≥ 100,000/μL without transfusion.
Haemoglobin ≥ 9.0 g/dL. Patients may be transfused to meet this criterion.
INR or aPTT ≤ 1.5 × upper limit of normal (ULN). This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN, with the following exceptions: Patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN. Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 × ULN.
Serum bilirubin ≤ 1.25 × ULN. Patients with known Gilbert disease who have serum bilirubin level ≤ 3 × ULN may be enrolled.
Serum creatinine ≤ 1.5 × ULN or creatinine clearance of ≥45ml/min (based on the Cockcroft Gault formula).

All patients are notified of the investigational nature of this study and signed a written informed consent in accordance with institutional and national guidelines, including the Declaration of Helsinki prior to any trial-related intervention.
For female patients of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate (< 1% per year) when used consistently and correctly, and to continue its use for 5 months after the last dose of Atezolizumab and/or 6 months after the last dose of Bevacizumab, whichever is later. Such methods include: combined (oestrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD): intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence.
For male patients with female partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate [< 1% per year] when used consistently and correctly, and to continue its use for 6 months after the last dose of Bevacizumab. Male patients should not donate sperm during this study and for at least 6 months after the last dose of Bevacizumab.
Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drugs. The same rules are valid for male patients involved in this clinical study if they have a partner of childbirth potential. Male patients must always use a condom.
Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.

Exclusion Criteria:

Patients with a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene.
Patients with an anaplastic lymphoma kinase (ALK) fusion oncogene.
Patients with an STK-1 Ligand alteration.
Patients with MDM2 amplification.
Patients with ROS1 translocations.
Active or untreated CNS metastases as determined by CT or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments.
Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomization.
Leptomeningeal disease.
Uncontrolled tumour-related pain. Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to initiation of study drug. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for locoregional therapy, if appropriate, prior to initiation of study drug.
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX®) are allowed.
Uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN).
Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Clínico Universitario de Santiago	Santiago De Compostela	A Coruña	Spain	15706
2	Hospital General Universitario de Elche	Elche	Alicante	Spain	03203
3	ICO Badalona	Badalona	Barcelona	Spain	08916
4	Consorci Sanitari de Terrassa	Terrassa	Barcelona	Spain	08022
5	Complejo Hospitalario Universitario A Coruña	A Coruña	La Coruña	Spain	15006
6	Hospital Puerta de Hierro	Majadahonda	Madrid	Spain	28222
7	Hospital Universitario Son Espases	Palma De Mallorca	Mallorca	Spain	07120
8	Hospital Universitario Son Llàtzer	Palma De Mallorca	Mallorca	Spain	07198
9	Complexo Hospitalario Universitario de Vigo	Vigo	Pontevedra	Spain	36036
10	Hospital General de Alicante	Alicante		Spain	03010
11	Hospital Clínic de Barcelona	Barcelona		Spain	08036
12	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08041
13	Consorcio Hospitalario Provincial de Castelló	Castelló		Spain	12004
14	Hospital Universitario Reina Sofía	Córdoba		Spain	14004
15	Complejo Hospitalario de Jaén	Jaén		Spain	23007
16	Hospital Universitario Lucus Augusti	Lugo		Spain	27003
17	Hospital La Princesa	Madrid		Spain	28006
18	Hospital Clínico San Carlos	Madrid		Spain	28040
19	Hospital Universitario Fundación Jiménez Díaz	Madrid		Spain	28040
20	Hospital General Universitario de Málaga	Málaga		Spain	29010
21	Complejo Hospitalario de Toledo	Toledo		Spain	45004
22	Hospital Universitari i Politécnic La Fe	Valencia		Spain	46009
23	Hospital Clínico Universitario de Valencia	Valencia		Spain	46010
24	Hospital General de Valencia	Valencia		Spain	46014
25	Hospital Clínico Universitario de Valladolid	Valladolid		Spain	47003