Best EGFR-TKI Sequence in NSCLC Harboring EGFR Mutations

NCT04811001 | Unknown Phase 2

• 1 other identifier: CAPLAND
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 20

Brief Summary

The best drug sequencing of dacomitinib or osimertinib in patients with advanced or metastatic Epidermal Growth Factor Receptor (EGFR) mutation positive non-small-cell lung cancer (NSCLC) has not yet been determined. The study enables investigation of the efficacy of dacomitinib followed by or subsequent to osimertinib osimertinib in patients with classical or uncommon activating EGFR mutations. Efficacy of dacomitinib will be defined in patients with asymptomatic or controlled brain metastases, special population eligible in this clinical trial.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS defined as the time from randomization to the date of death due to any cause, or to the date of censoring at the last time the subject was known to be alive

  Up to 2 years since last patient enrolled

Secondary Outcomes (4)

• Progresison Free Survival (PFS1)

  Up to 2 years since last patient enrolled

• Progresison Free Survival (PFS2)

  Up to 2 years since last patient enrolled

• Response Rate (RR)

  At 1 year and 2 years

• Adverse Events

  During the trial, untill 2 years

Study Arms (2)

Arm A (Osimertinib->Dacomitinib)

EXPERIMENTAL

Osimertinib 80 mg/day until progression, unacceptable toxicity or patient refusal. At treatment discontinuation patients maintaining the original EGFR mutation will switch to Dacomitinib 45 mg/day until progression, unacceptable toxicity or patient refusal.

Drug: Osimertinib; Drug: Dacomitinib

Arm B (Dacomitinib->Osimertinib)

EXPERIMENTAL

Dacomitinib 45 mg/day until progression, unacceptable toxicity or patient refusal. At treatment discontinuation, patients harboring the EGFR-T790M will receive Osimertinib 80 mg/day until progression, unacceptable toxicity or patient refusal.

Drug: Osimertinib; Drug: Dacomitinib

Interventions

Osimertinib DRUG

TAGRISSO 40 mg film-coated tablets TAGRISSO 80 mg film-coated tablets

Also known as: Tagrisso

Arm A (Osimertinib->Dacomitinib); Arm B (Dacomitinib->Osimertinib)

Dacomitinib DRUG

Vizimpro 15 mg film-coated tablets Vizimpro 30 mg film-coated tablets Vizimpro 45 mg film-coated tablets

Also known as: Vizimpro

Arm A (Osimertinib->Dacomitinib); Arm B (Dacomitinib->Osimertinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent;
• Male or female patient aged ≥18 years;
• Patients eligible and candidate to receive osimertinib as first- or second-line treatment according to clinical practice and study design, as decided by Investigator regardless study participation;
• Patients with brain metastases are allowed provided they are asymptomatic and stable (i.e. without evidence of progression by imaging for at least two weeks prior to the first dose of trial treatment and without deterioration of any neurologic symptoms);
• No evidence of concomitant drivers including KRAS mutations, HER2 mutations, ALK or ROS1 rearrangements, MET mutations, BRAF mutations;
• No previous EGFR-TKI therapy; Previous palliative radiotherapy or surgery allowed. Prior brain radiotherapy and Stereotactic Radiosurgery (SRS) are allowed. Previous neo/adjuvant chemotherapy is allowed as long as therapy was completed at least 6 months before diagnosis of advanced or metastatic NSCLC;
• At least one radiological measurable disease according to RECIST criteria version 1.1;
• Performance status 0-1 (ECOG PS);
• Patient compliance to trial procedures;
• Adequate bone marrow function (ANC ≥ 1.5x109/L, platelets ≥100x109/L, haemoglobin \>9 g/dl);
• Adequate liver function (AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN, bilirubin \< grade 2, transaminases no more than 3xULN/\<5xULN in presence of liver metastases);
• Normal level of alkaline phosphatase, and creatinine;
• Female patients should be using adequate contraceptive measures, should not be breastfeeding, until 12 months after the last dose, and must have a negative pregnancy test (serum or urine) prior to first dose of study drug (within 72 hours); or female patients must have an evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
• 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 luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution. Documentation of irreversible surgical by hysterectomy, bilateraloophorectomy, or bilateral salpingectomy but not tubal ligation.

You may not qualify if:

• Previous therapy with any EGFR-TKI;
• Previous systemic anti-cancer therapy for advanced/metastatic NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug;
• Absence of measurable lesions;
• Concomitant radiotherapy or chemotherapy;
• Symptomatic or immediately requiring therapy brain metastases or carcinomatous meningitis. Subjects with asymptomatic and stable or treated brain metastases may participate;
• Diagnosis of any other malignancy during the last 3 years, except for in situ carcinoma of cervix uteri and squamous cell carcinoma of the skin;
• History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis (but not history of prior radiation pneumonitis);
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV);
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of the study drugs;
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \>470 msec, obtained from 3 ECGs using local clinic ECG machine-derived QTcF value;
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval \>250 msec or history of episodes of bradycardia (\<50 BPM);
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as 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;
• Abnormal cardiac function: LVEF \< 50% (assessed by MUGA or ECHO)
• Pregnancy or lactating female;

Sponsors & Collaborators

• Fondazione Ricerca Traslazionale: lead

Study Sites (20)

Istituto Toscano Tumori Ospedale San Donato

Arezzo, AR, 52100, Italy

NOT YET RECRUITING

IRCCS Istituto Tumori "Giovanni Paolo II"

Bari, BA, 70124, Italy

ACTIVE NOT RECRUITING

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)

Meldola, FC, 47014, Italy

NOT YET RECRUITING

ca Azienda OspedalieroUniversitaria Caregg

Florence, FI, 50134, Italy

NOT YET RECRUITING

IRCCS AOU San Martino IST - Istituto Nazionale per la Ricerca sul Cancro

Genova, GE, 16132, Italy

NOT YET RECRUITING

Ospedale Versilia

Lido di Camaiore, LU, 55041, Italy

NOT YET RECRUITING

Ospedale San Luca

Lucca, LU, 55100, Italy

NOT YET RECRUITING

AOU - Policlinico di Modena

Modena, MO, 41100, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Paolo Giaccone

Palermo, PA, 90127, Italy

ACTIVE NOT RECRUITING

Casa di Cura La Maddalena

Palermo, PA, 90146, Italy

NOT YET RECRUITING

Istituto Oncologico Veneto

Padua, PD, 35128, Italy

RECRUITING

Centro di Riferimento Oncologico di Basilicata

Rionero in Vulture, PZ, 85028, Italy

ACTIVE NOT RECRUITING

RCCS- Arcispedale Santa Maria Nuova

Reggio Emilia, RE, 42123, Italy

NOT YET RECRUITING

Istituto Nazionale Tumori "Regina Elena"

Roma, RM, 00144, Italy

RECRUITING

Ospedale Civile SS. Annunziata

Sassari, SS, 07100, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliera S. Maria di Terni

Terni, TR, 05100, Italy

NOT YET RECRUITING

A.O. Busto Arsizio P.O. Saronno

Saronno, VA, 21047, Italy

ACTIVE NOT RECRUITING

ASST Sette Laghi

Varese, VA, 21100, Italy

NOT YET RECRUITING

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, 80131, Italy

RECRUITING

A.O.U. "Maggiore della Carità

Novara, 28100, Italy

RECRUITING

MeSH Terms

Interventions

osimertinib; dacomitinib

Study Officials

• Alessandro Morabito, MD

  Istituto Nazionale Tumori IRCCS Fondazione Pascale

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Federico Cappuzzo, MD

CONTACT

+39 0652665698; f.cappuzzo@gmail.com

Lorenza Landi, MD

CONTACT

+39 0652665698; landi.lorenza@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, non-comparative study investigating two EGFR-TKI sequences

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: March 23, 2021
• Study Start: June 12, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: February 21, 2023

Record last verified: 2023-02

Locations

IT (20)