ALK Gene Rearrangement PositivePhase 2NCT03779191

Alectinib in Combination With Bevacizumab in ALK Positive NSCLC

A Phase 2 study testing Alectinib and Bevacizumab in people with ALK Gene Rearrangement Positive and Non-Squamous Non-Small Cell Neoplasm of Lung, run by Instituto Nacional de Cancerologia de Mexico at 1 site in Mexico.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This single-arm, open-label, phase II clinical study aims to evaluate the progression-Free Survival (PFS) of the combination of Alectinib plus Bevacizumab in untreated and first and second-line chemotherapy failed subjects with stage IIIB/IV or recurrent disease after receiving radiation therapy or surgical resection. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: ALK Gene Rearrangement Positive, Non-Squamous Non-Small Cell Neoplasm of Lung
What is being tested?: Alectinib and Bevacizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 41 participants
Where: 1 siteMexico
Study dates: 8 Apr 2020to 30 Oct 2022
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Men and women, ≥18 years of age.
Subjects with NSCLC with known ALK-rearrangement tested with FDA-approved test (IHQ or FISH).
Subjects with sufficient tissue to test for ALK-rearranged using IHQ or FISH.
Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
Karnofsky Performance Status of ≥70
Subjects with histologically confirmed Stage 3B (IIIB), 4 (IV) or recurrent NSCLC (per the 8th International Association for the Study of Lung Cancer classification, non-squamous histology, with prior systemic chemotherapy (platinum-based) given as primary therapy for advanced disease. Prior adjuvant or neoadjuvant chemotherapy is permitted as long as the last administration of the prior regimen occurred at least 3 weeks prior to enrollment. Prior treatment with ALK inhibitors is permitted as long as the last administration occurred 3 weeks prior to enrollment.

Show all 20Show fewer

Subjects with CNS metastases are only eligible if the CNS metastases are adequately treated with radiotherapy and/or surgery and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 1 week prior to randomization.
Patients receiving radiotherapy or radiosurgery with a dose exceeding 30 Gy will have 3 weeks for neurological stabilization before randomization.
This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
Measurable disease by CT as per RECIST 1.1 criteria.
The target lesions may be located on a previously irradiated field exists if documented progression of disease (radiographic) in that site.
At least 12 weeks of life expectancy.
Signed written informed consent
Patients should have a signed and dated form of written informed consent approved by the institutional committee in accordance with regulatory and institutional guidelines. This must be obtained before performing any procedure related to the protocol that are not part of the normal care of the patient.
Patients must be willing and able to comply with scheduled visits, treatment program, laboratory testing including filling of questionnaires the results reported by the patient and other study requirements.
Reproductive Status
Women with reproductive potential (WOCBP) should use contraceptive methods based on tables found in Appendix 2. When a teratogenic drug test is used, and / or a drug for which there is not enough information to assess teratogenicity (have not been conducted preclinical studies) are required to use a highly effective method of contraception (failure rate less than 1 % per year). Individual methods of contraception should be determined in consultation with the researcher.
The WOCBP must have a negative pregnancy test in serum or urine (minimum sensitivity 25 IU / L or equivalent units of HCG) 24 hours before starting the investigational product.
Women should not be breastfeeding.
Sexually active men WOCBP should use any method of contraception with a failure rate of less than 1% per year. The investigator should review contraceptive methods and the time period during which contraception to use. Men who are sexually active with WOCBP, follow the instructions of birth control for a period of 90 days, plus the time required for the investigational drug is subject to five half-lives

Who cannot join

Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 [L858R] substitution mutations) are excluded. All subjects with non-squamous histology must have been tested locally for EGFR mutation status; use of an FDA-approved test is strongly encouraged (EGFR mutation testing may be performed during the Screening Period, Non-squamous subjects with unknown or indeterminate EGFR status may not be included).
Subjects with untreated CNS metastases are excluded.
Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as Vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
Treatment with other investigational drugs or other anti-cancer therapy, or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with this trial
Radiographical evidence of cavitated or necrotic tumors

Show all 33Show fewer

Centrally located tumors with radiographical evidence (CT or MRI) of local invasion of major blood vessels
History of clinically significant hemoptysis within the past 3 months
History of major thrombotic or clinically relevant major bleeding event in the past 6 months.
Known inherited predisposition to bleeding or thrombosis
Medical History and Concurrent Diseases
Any medical condition or serious uncontrolled or active infection with hepatitis or HIV that could be reactivated.
Other concurrent malignancies requiring intervention.
All toxicities attributed to a previous treatment for cancer other than alopecia or fatigue, must have resolved to Grade 1 (NCI CTCAE version 4) or baseline, prior to administration of study drug.
Prior treatment with tumor vaccines or other anti-tumor immune stimulating agents.
Prior treatment with Alectinib.
Prior treatment with Bevacizumab
Subjects with a history of interstitial lung disease.
Subjects must be recovered from the effects of major surgery, traumatic injury or substantially at least 7 days before the first dose of study treatment.
Physical Findings and Laboratory Tests
Positive for the surface antigen of hepatitis B virus (HBV HBsAg) or hepatitis C ribonucleic acid (HCV RNA) Evidence indicating acute or chronic infection
Known history of positive test for Human Immunodeficiency Virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS).
Allergies and Adverse Drug Reactions to
History of severe hypersensitivity to other monoclonal antibodies.
Previous history of severe hypersensitivity reaction to paclitaxel.
History of allergy or intolerance (unacceptable adverse event) to components of the study drug, or herbal teas that contain Polysorbate 80.
Sexual and Reproductive Status
WOCBP pregnant or who are nursing
Women with a positive pregnancy test in recruitment or prior to administration of the study drug.
Other Exclusion Criteria
Any other serious medical condition or uncontrolled active infection, findings on physical examination, laboratory findings, altered mental status, or psychiatric condition that, in the investigator's opinion, would limit the ability of an individual to meet the requirements of study, significantly increase the risk to the subject, or which affects the interpretability of the study results.
Prisoners or subjects who are involuntarily incarcerated.
Subjects who are compulsorily admitted for treatment of a mental or physical illness (eg, infectious disease). Eligibility criteria for this study were carefully considered to ensure the safety of study subjects, and to ensure that the results of the study can be used

Trial locations and contacts

1 site in 1 country.

Mexico1 site

Instituto Nacional de Cancerologia
Mexico City, 14080

Other trials in Mexico

About this study

Official title: Phase II, Open Label, Single Arm Trial of Alectinib in Combination With Bevacizumab in Untreated and Previously Treated Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) With Positive ALK Driver Mutation

The main question to be answered is:

Whether the combination of Alectinib plus Bevacizumab will improve PFS in untreated and previously treated subjects with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) and positive ALK translocation.

Participants will be treated with Alectinib and Bevacizumab every three weeks until disease progression, unacceptable toxicity, or patient withdrawal of consent.

Read the detailed description

Dose selection The required dose amount for Alectinib is based on a fixed dose of 600 mg, and the dose for Bevacizumab when preparing the solution is based on the subject's weight in kilograms (kg).

Dose Modification The administration of Alectinib/Bevacizumab will be stopped in case of Grade 4 hematological toxicities or Grade 3 non-hematological drug-related toxicities, including severe or life-threatening abnormalities.

The test treatment should be discontinued if toxicity does not resolve to grade 0-1 within 12 weeks after the last application.

With an adverse laboratory event still graded two, after 12 weeks, they can continue treatment at trial only if the reaction is asymptomatic and controlled.

Subjects who experience a recurrence of the same severe or life-threatening event to the same or greater degree with a re-challenge of alectinib/bevacizumab should discontinue the trial treatment.

Conditions: ALK Gene Rearrangement Positive, Non-Squamous Non-Small Cell Neoplasm of Lung
Being tested: Alectinib, Bevacizumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AlectinibDrug
Also called Alecensa
Alectinib dosed 600 mg twice a day (BID) with meals until disease progression, unacceptable toxicity, or other reasons specified in the protocol
BevacizumabDrug
Also called Avastin
Bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression, unacceptable toxicity, or other reasons specified in the protocol

Study groups in NCT03779191
Study group	Role	What they receive
Intervention	Experimental	Patients in this intervention arm will receive the therapeutic combination of Alectinib dosed PO 600 mg bis in die (BID) with meals and Bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression, unacceptable toxicity, or other reasons specified in the protocol Receives: Drug: Alectinib; Drug: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Progression-free survival
PFS based on response criteria according to RECIST 1.1 in untreated and previously treated patients with Advanced or metastatic ALK-rearranged Non-Squamous NSCLC who receive treatment with Alectinib plus Bevacizumab
Measured: Through study completion, an average of 18 months

Secondary outcomes (7)

Objective response rate
To assess the ORR, based on response criteria according to RECIST 1.1, in untreated and previously treated patients with Advanced or Metastatic ALK-rearranged Non-Squamous NSCLC who receive treatment with Alectinib plus Bevacizumab.
Measured: 8 weeks
Brain- ORR
To assess the brain ORR, based on response criteria according RECIST 1.1, in untreated and previously treated patients with Advanced or metastatic Non-Squamous NSCLC who receive treatment with Alectinib plus Bevacizumab.
Measured: 8 weeks
Overall survival
To assess the OS in untreated and previously treated patients with Advanced or metastatic Non-Squamous ALK-rearranged NSCLC who receive treatment with Alectinib plus Bevacizumab.
Measured: Through study completion, an average of 18 months
Time to developing brain metastases
To assess the time since inclusion until developing brain metastases in untreated and previously treated patients with Advanced or metastatic Non-Squamous ALK-rearranged NSCLC who receive treatment with Alectinib plus Bevacizumab.
Measured: Through study completion, an average of 18 months
Change From Baseline in Global Quality of Life (QOL), Functional Scales and Symptoms Scales as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) During Overall Treatment
The EORTC QLQ C30 consists of 30 questions and includes 5 functional scales (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale; 3 symptom scales (fatigue, pain, nausea, and vomiting); and 6 single items that assess additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and financial impact. All scales and single-item measures range in scores from 0 to 100. Higher scores on the functional scales represent higher levels of functioning. Higher scores on the global health status/quality of life scale represent higher health status/quality of life. Higher scores on symptom scales/items represent a greater presence of symptoms.
Measured: From Baseline up to Cycle 20 (each cycle is 3 weeks) Day 1.
Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment
The EORTC QLQ LC13 consists of 13 questions and includes 1 multi-item scale and 9 single items assessing symptoms (dyspnea, cough, haemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication use. The scale scores rang from 0 to 100, with higher scores indicating higher ("worse") level of symptoms.
Measured: From Baseline up to Cycle 20 (each cycle is 3 weeks) Day 1.
Time to Deterioration (TTD) in Participant Reported Global Quality of Life, or Cough From QLQ-LC13
The EORTC QLQ C30 consists of 30 questions and includes 5 functional scales (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale; Higher scores on the global health status/quality of life scale represent higher health status/quality of life. TTD in pain in global Quality of Life was defined as the time from randomization to the first time the participant's score showed a 10 point or greater increase after baseline in any of the 3 symptoms. TTD in months was calculated as (date of deterioration or censoring - randomization date +1)/30.4375.
Measured: From Baseline up to Cycle 20 (each cycle is 3 weeks) Day 1.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Apr 202030 Oct 2022

First posted19 Dec 2018
Study start8 Apr 2020
Primary completion1 Aug 2022
Study completion30 Oct 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (9)Papers the sponsor has linked to this study.
Other trials for ALK Gene Rearrangement PositiveStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Phase II, single arm trial assessing Alectinib in combination with Bevacizumab in untreated and previously treated patients with Advanced or Metastatic Non-Squamous ALK-rearranged NSCLC
Masking: None (open label)
Enrolment: 41 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03779191
Sponsor's protocol ID: Alectinib plus Bevacizumab
Status last verified: Jul 2023
First submitted: 13 Dec 2018
Last updated: 6 Jul 2023
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Arrieta O, Guzman-de Alba E, Alba-Lopez LF, Acosta-Espinoza A, Alatorre-Alexander J, Alexander-Meza JF, Allende-Perez SR, Alvarado-Aguilar S, Araujo-Navarrete ME, Argote-Greene LM, Aquino-Mendoza CA, Astorga-Ramos AM, Austudillo-de la Vega H, Aviles-Salas A, Barajas-Figueroa LJ, Barroso-Quiroga N, Blake-Cerda M, Cabrera-Galeana PA, Calderillo-Ruiz G, Campos-Parra AD, Cano-Valdez AM, Capdeville-Garcia D, Castillo-Ortega G, Casillas-Suarez C, Castillo-Gonzalez P, Corona-Cruz JF, Correa-Acevedo ME, Cortez-Ramirez SS, de la Cruz-Vargas JA, de la Garza-Salazar JG, de la Mata-Moya MD, Dominguez-Flores ME, Dominguez-Malagon HR, Dominguez-Parra LM, Dominguez-Peregrina A, Duran-Alcocer J, Enriquez-Aceves MI, Elizondo-Rios A, Escobedo-Sanchez MD, de Villafranca PE, Flores-Cantisani A, Flores-Gutierrez JP, Franco-Marina F, Franco-Gonzalez EE, Franco-Topete RA, Fuentes-de la Pena H, Galicia-Amor S, Gallardo-Rincon D, Gamboa-Dominguez A, Garcia-Andreu J, Garcia-Cuellar CM, Garcia-Sancho-Figueroa MC, Garcia-Torrentera R, Gerson-Cwilich R, Gomez-Gonzalez A, Green-Schneeweiss L, Guillen-Nunez Mdel R, Gutierrez-Velazquez H, Ibarra-Perez C, Jimenez-Fuentes E, Juarez-Sanchez P, Juarez-Ramiro A, Kelly-Garcia J, Kuri-Exsome R, Lazaro-Leon JM, Leon-Rodriguez E, Llanos-Osuna S, Llanos-Osuna S, Loyola-Garcia U, Lopez-Gonzalez JS, Lopez y de Antunano FJ, Loustaunau-Andrade MA, Macedo-Perez EO, Machado-Villarroel L, Magallanes-Maciel M, Martinez-Barrera L, Martinez-Cedillo J, Martinez-Martinez G, Medina-Esparza A, Meneses-Garcia A, Mohar-Betancourt A, Morales Blanhir J, Morales-Gomez J, Motola-Kuba D, Najera-Cruz MP, Nunez-Valencia Cdel C, Ocampo-Ocampo MA, Ochoa-Vazquez MD, Olivares-Torres CA, Palomar-Lever A, Patino-Zarco M, Perez-Padilla R, Pena-Alonso YR, Perez-Romo AR, Aquilino Perez M, Pinaya-Ruiz PM, Pointevin-Chacon MA, Poot-Braga JJ, Posadas-Valay R, Ramirez-Marquez M, Reyes-Martinez I, Robledo-Pascual J, Rodriguez-Cid J, Rojas-Marin CE, Romero-Bielma E, Rubio-Gutierrez JE, Saenz-Frias JA, Salazar-Lezama MA, Sanchez-Lara K, Sansores Martinez R, Santillan-Doherty P, Alejandro-Silva J, Tellez-Becerra JL, Toledo-Buenrostro V, Torre-Bouscoulet L, Torecillas-Torres L, Torres M, Tovar-Guzman V, Turcott-Chaparro JG, Vazquez-Cortes JJ, Vazquez-Manriquez ME, Vilches-Cisneros N, Villegas-Elizondo JF, Zamboni MM, Zamora-Moreno J, Zinser-Sierra JW. [National consensus of diagnosis and treatment of non-small cell lung cancer]. Rev Invest Clin. 2013 Mar;65 Suppl 1:S5-84. Spanish.
PubMed 24459776
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. Epub 2015 Feb 4.
PubMed 25651787
Spiro SG, Silvestri GA. One hundred years of lung cancer. Am J Respir Crit Care Med. 2005 Sep 1;172(5):523-9. doi: 10.1164/rccm.200504-531OE. Epub 2005 Jun 16.
PubMed 15961694
Choi YL, Soda M, Yamashita Y, Ueno T, Takashima J, Nakajima T, Yatabe Y, Takeuchi K, Hamada T, Haruta H, Ishikawa Y, Kimura H, Mitsudomi T, Tanio Y, Mano H; ALK Lung Cancer Study Group. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med. 2010 Oct 28;363(18):1734-9. doi: 10.1056/NEJMoa1007478.
PubMed 20979473
Ou SH, Bartlett CH, Mino-Kenudson M, Cui J, Iafrate AJ. Crizotinib for the treatment of ALK-rearranged non-small cell lung cancer: a success story to usher in the second decade of molecular targeted therapy in oncology. Oncologist. 2012;17(11):1351-75. doi: 10.1634/theoncologist.2012-0311. Epub 2012 Sep 18.
PubMed 22989574
Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007 Aug 2;448(7153):561-6. doi: 10.1038/nature05945. Epub 2007 Jul 11.
PubMed 17625570
Inamura K, Takeuchi K, Togashi Y, Nomura K, Ninomiya H, Okui M, Satoh Y, Okumura S, Nakagawa K, Soda M, Choi YL, Niki T, Mano H, Ishikawa Y. EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. J Thorac Oncol. 2008 Jan;3(1):13-7. doi: 10.1097/JTO.0b013e31815e8b60.
PubMed 18166835
Doebele RC, Pilling AB, Aisner DL, Kutateladze TG, Le AT, Weickhardt AJ, Kondo KL, Linderman DJ, Heasley LE, Franklin WA, Varella-Garcia M, Camidge DR. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012 Mar 1;18(5):1472-82. doi: 10.1158/1078-0432.CCR-11-2906. Epub 2012 Jan 10.
PubMed 22235099
Pulford K, Lamant L, Morris SW, Butler LH, Wood KM, Stroud D, Delsol G, Mason DY. Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALK1. Blood. 1997 Feb 15;89(4):1394-404.
PubMed 9028963

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All ALK Gene Rearrangement Positive trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase II, Open Label, Single Arm Trial of Alectinib in Combination With Bevacizumab in Untreated and Previously Treated Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) With Positive ALK Driver Mutation
ClinicalTrials.gov ID: NCT03779191
Acronym / sponsor ID: Alectinib plus Bevacizumab
Conditions: ALK Gene Rearrangement Positive, Non-Squamous Non-Small Cell Neoplasm of Lung
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 41 participants (actual)
Lead sponsor: Instituto Nacional de Cancerologia de MexicoUniversity, hospital or other
Collaborators: Roche Pharma AG
Study start: 8 Apr 2020 (actual)
Primary completion: 1 Aug 2022 (actual)
Study completion: 30 Oct 2022 (actual)
First posted: 19 Dec 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The main question to be answered is:

Participants will be treated with Alectinib and Bevacizumab every three weeks until disease progression, unacceptable toxicity, or patient withdrawal of consent.

Detailed description

Dose selection The required dose amount for Alectinib is based on a fixed dose of 600 mg, and the dose for Bevacizumab when preparing the solution is based on the subject's weight in kilograms (kg).

The test treatment should be discontinued if toxicity does not resolve to grade 0-1 within 12 weeks after the last application.

With an adverse laboratory event still graded two, after 12 weeks, they can continue treatment at trial only if the reaction is asymptomatic and controlled.

Subjects who experience a recurrence of the same severe or life-threatening event to the same or greater degree with a re-challenge of alectinib/bevacizumab should discontinue the trial treatment.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Phase II, single arm trial assessing Alectinib in combination with Bevacizumab in untreated and previously treated patients with Advanced or Metastatic Non-Squamous ALK-rearranged NSCLC

Arm	Type	Receives
Intervention	Experimental	Drug: Alectinib, Drug: BevacizumabPatients in this intervention arm will receive the therapeutic combination of Alectinib dosed PO 600 mg bis in die (BID) with meals and Bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression, unacceptable toxicity, or other reasons specified in the protocol

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (20 listed)

Men and women, ≥18 years of age.
Subjects with NSCLC with known ALK-rearrangement tested with FDA-approved test (IHQ or FISH).
Subjects with sufficient tissue to test for ALK-rearranged using IHQ or FISH.
Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
Karnofsky Performance Status of ≥70

Key exclusion criteria (33 listed)

Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 [L858R] substitution mutations) are excluded. All subjects with non-squamous histology must have been tested locally for EGFR mutation status; use of an FDA-approved test is strongly encouraged (EGFR mutation testing may be performed during the Screening Period, Non-squamous subjects with unknown or indeterminate EGFR status may not be included).
Subjects with untreated CNS metastases are excluded.
Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as Vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
Treatment with other investigational drugs or other anti-cancer therapy, or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with this trial

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AlectinibAlso: AlecensaAlectinib dosed 600 mg twice a day (BID) with meals until disease progression, unacceptable toxicity, or other reasons specified in the protocol	Drug	Intervention
BevacizumabAlso: AvastinBevacizumab 15 mg/kg intravenously every 3 weeks until disease progression, unacceptable toxicity, or other reasons specified in the protocol	Drug	Intervention

Primary outcome

Progression-free survival
Time frame: Through study completion, an average of 18 months
PFS based on response criteria according to RECIST 1.1 in untreated and previously treated patients with Advanced or metastatic ALK-rearranged Non-Squamous NSCLC who receive treatment with Alectinib plus Bevacizumab

7 secondary outcomes

Objective response rate
Time frame: 8 weeks
Brain- ORR
Time frame: 8 weeks
Overall survival
Time frame: Through study completion, an average of 18 months
Time to developing brain metastases
Time frame: Through study completion, an average of 18 months
Change From Baseline in Global Quality of Life (QOL), Functional Scales and Symptoms Scales as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) During Overall Treatment
Time frame: From Baseline up to Cycle 20 (each cycle is 3 weeks) Day 1.
Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment
Time frame: From Baseline up to Cycle 20 (each cycle is 3 weeks) Day 1.
Time to Deterioration (TTD) in Participant Reported Global Quality of Life, or Cough From QLQ-LC13
Time frame: From Baseline up to Cycle 20 (each cycle is 3 weeks) Day 1.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2023.
Background: PubMed 24459776Arrieta O, Guzman-de Alba E, Alba-Lopez LF, Acosta-Espinoza A, Alatorre-Alexander J, Alexander-Meza JF, Allende-Perez SR, Alvarado-Aguilar S, Araujo-Navarrete ME, Argote-Greene LM, Aquino-Mendoza CA, Astorga-Ramos AM, Austudillo-de la Vega H, Aviles-Salas A, Barajas-Figueroa LJ, Barroso-Quiroga N, Blake-Cerda M, Cabrera-Galeana PA, Calderillo-Ruiz G, Campos-Parra AD, Cano-Valdez AM, Capdeville-Garcia D, Castillo-Ortega G, Casillas-Suarez C, Castillo-Gonzalez P, Corona-Cruz JF, Correa-Acevedo ME, Cortez-Ramirez SS, de la Cruz-Vargas JA, de la Garza-Salazar JG, de la Mata-Moya MD, Dominguez-Flores ME, Dominguez-Malagon HR, Dominguez-Parra LM, Dominguez-Peregrina A, Duran-Alcocer J, Enriquez-Aceves MI, Elizondo-Rios A, Escobedo-Sanchez MD, de Villafranca PE, Flores-Cantisani A, Flores-Gutierrez JP, Franco-Marina F, Franco-Gonzalez EE, Franco-Topete RA, Fuentes-de la Pena H, Galicia-Amor S, Gallardo-Rincon D, Gamboa-Dominguez A, Garcia-Andreu J, Garcia-Cuellar CM, Garcia-Sancho-Figueroa MC, Garcia-Torrentera R, Gerson-Cwilich R, Gomez-Gonzalez A, Green-Schneeweiss L, Guillen-Nunez Mdel R, Gutierrez-Velazquez H, Ibarra-Perez C, Jimenez-Fuentes E, Juarez-Sanchez P, Juarez-Ramiro A, Kelly-Garcia J, Kuri-Exsome R, Lazaro-Leon JM, Leon-Rodriguez E, Llanos-Osuna S, Llanos-Osuna S, Loyola-Garcia U, Lopez-Gonzalez JS, Lopez y de Antunano FJ, Loustaunau-Andrade MA, Macedo-Perez EO, Machado-Villarroel L, Magallanes-Maciel M, Martinez-Barrera L, Martinez-Cedillo J, Martinez-Martinez G, Medina-Esparza A, Meneses-Garcia A, Mohar-Betancourt A, Morales Blanhir J, Morales-Gomez J, Motola-Kuba D, Najera-Cruz MP, Nunez-Valencia Cdel C, Ocampo-Ocampo MA, Ochoa-Vazquez MD, Olivares-Torres CA, Palomar-Lever A, Patino-Zarco M, Perez-Padilla R, Pena-Alonso YR, Perez-Romo AR, Aquilino Perez M, Pinaya-Ruiz PM, Pointevin-Chacon MA, Poot-Braga JJ, Posadas-Valay R, Ramirez-Marquez M, Reyes-Martinez I, Robledo-Pascual J, Rodriguez-Cid J, Rojas-Marin CE, Romero-Bielma E, Rubio-Gutierrez JE, Saenz-Frias JA, Salazar-Lezama MA, Sanchez-Lara K, Sansores Martinez R, Santillan-Doherty P, Alejandro-Silva J, Tellez-Becerra JL, Toledo-Buenrostro V, Torre-Bouscoulet L, Torecillas-Torres L, Torres M, Tovar-Guzman V, Turcott-Chaparro JG, Vazquez-Cortes JJ, Vazquez-Manriquez ME, Vilches-Cisneros N, Villegas-Elizondo JF, Zamboni MM, Zamora-Moreno J, Zinser-Sierra JW. [National consensus of diagnosis and treatment of non-small cell lung cancer]. Rev Invest Clin. 2013 Mar;65 Suppl 1:S5-84. Spanish.
Background: PubMed 25651787Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. Epub 2015 Feb 4.
Background: PubMed 15961694Spiro SG, Silvestri GA. One hundred years of lung cancer. Am J Respir Crit Care Med. 2005 Sep 1;172(5):523-9. doi: 10.1164/rccm.200504-531OE. Epub 2005 Jun 16.
Background: PubMed 20979473Choi YL, Soda M, Yamashita Y, Ueno T, Takashima J, Nakajima T, Yatabe Y, Takeuchi K, Hamada T, Haruta H, Ishikawa Y, Kimura H, Mitsudomi T, Tanio Y, Mano H; ALK Lung Cancer Study Group. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med. 2010 Oct 28;363(18):1734-9. doi: 10.1056/NEJMoa1007478.
Background: PubMed 22989574Ou SH, Bartlett CH, Mino-Kenudson M, Cui J, Iafrate AJ. Crizotinib for the treatment of ALK-rearranged non-small cell lung cancer: a success story to usher in the second decade of molecular targeted therapy in oncology. Oncologist. 2012;17(11):1351-75. doi: 10.1634/theoncologist.2012-0311. Epub 2012 Sep 18.
Background: PubMed 17625570Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007 Aug 2;448(7153):561-6. doi: 10.1038/nature05945. Epub 2007 Jul 11.
Background: PubMed 18166835Inamura K, Takeuchi K, Togashi Y, Nomura K, Ninomiya H, Okui M, Satoh Y, Okumura S, Nakagawa K, Soda M, Choi YL, Niki T, Mano H, Ishikawa Y. EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. J Thorac Oncol. 2008 Jan;3(1):13-7. doi: 10.1097/JTO.0b013e31815e8b60.
Background: PubMed 22235099Doebele RC, Pilling AB, Aisner DL, Kutateladze TG, Le AT, Weickhardt AJ, Kondo KL, Linderman DJ, Heasley LE, Franklin WA, Varella-Garcia M, Camidge DR. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012 Mar 1;18(5):1472-82. doi: 10.1158/1078-0432.CCR-11-2906. Epub 2012 Jan 10.
Background: PubMed 9028963Pulford K, Lamant L, Morris SW, Butler LH, Wood KM, Stroud D, Delsol G, Mason DY. Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALK1. Blood. 1997 Feb 15;89(4):1394-404.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Oscar G Arrieta Rodriguez, M.D., M.Sc. principal investigator

Instituto Nacional de Cancerología de México

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (time frame: Through study completion, an average of 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03779191, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2023.