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Non Small Cell Lung Cancer MetastaticPhase 2R2D2NCT03845270

Her2-positive Lung Cancer Treated With Dedicated Drug

A Phase 2 study testing pertuzumab + trastuzumab + docetaxel in people with Non Small Cell Lung Cancer Metastatic and Non Small Cell Lung Cancer Stage III, run by Intergroupe Francophone de Cancerologie Thoracique at 18 sites in France.

Completed

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

Official record
Search all trials

Trial summary

HER2 (erbB-2/neu) is a member of the erbB receptor tyrosine kinase family. ERBB2 gene which encodes human epidermal growth factor 2 (HER2) is a major proliferative driver activating downstream signaling through PI3K-AKT and MEK-ERK. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
pertuzumab + trastuzumab + docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
18 sitesFrance
Study dates
17 May 2019to 18 Dec 2023
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

  • Patient having signed an informed consent form
  • Histologically or cytologically confirmed NSCLC (per 2015 8th edition TNM classification)
  • Not suitable for radiation, inoperable stage III or stage IV
  • HER2 exon 20 mutation or insertion among which: in-frame insertions in exon 20 between codons 775 and 881 including the 12bp insertion with a duplication / insertion of 4 amino acids (YVMA) at codon 775, the 3bp insertion with a complex insertion-substitution G776>VC and point mutations L755S and G776C. Other mutation/insertion should be discussed with IFCT. Analysis must be performed in INCa-labelled laboratories or platforms according to a validated procedure.
  • Prior treatment with at least one regimen of platinum-based chemotherapy with documented disease progression.
  • Note: taxanes are allowed provided that no grade >2 associated adverse event occurred (except hematological toxicity).
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  • Presence of at least one lesion that can be measured by CT scan (RECIST v1.1)
  • Age ≥ 18 years
  • Adequate organ function, as evidenced by the following laboratory results:
  • ANC > 1500 cells/mm3 Platelet count > 100,000 cells/mm3 Hemoglobin > 9.0 g/dL Patients are allowed to receive transfused RBC to achieve this level. Total bilirubin ≤ 1.5 × ULN, except in patients with previously documented Gilbert's syndrome, in which case the direct bilirubin should be less than or equal to the ULN SGOT and SGPT ≤ 2.5 × ULN Alkaline phosphatase ≤ 2.5 × ULN, Alkaline phosphatase < 5×ULN and SGOT and SGPT < 5×ULN for patients with hepatic and/or bone metastases Clearance creatinine ≥ 30 mL/min INR and aPTT ≤ 1.5 x ULN This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
  • WHO performance index of 0, 1 or 2
  • LVEF ≥ 50%
  • Patient who is capable, according to the investigator, of complying with the study's requirements and restrictions
  • Estimated life expectancy > 3 months
  • A female is eligible to enter and participate in this study if she is of:
  • Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has undergone:
  • Hysterectomy.
  • Bilateral oophorectomy (ovariectomy).
  • Bilateral tubal ligation.
  • Or who is post-menopausal:
  • Patients not using hormone replacement therapy (HRT) must have experienced total cessation of menses for ≥1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone value >40 mIU/mL and an estradiol value <40 pg/mL (<140 pmol/L).
  • Patients must discontinue HRT prior to study enrolment due to the potential for inhibition of cytochrome enzymes that metabolize estrogens and progestins. For most forms of HRT, at least 2 4 weeks must elapse between the cessation of HRT and determination of menopausal status; length of this interval depends on the type and dosage of HRT. If a female subject is determined not to be post-menopausal, they must use adequate contraception, as defined immediately below.
  • Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception during the study and for at least 7 months after the last dose of investigational product. Contraceptive methods acceptable to IFCT, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:
  • A non-hormonal intrauterine device with a documented failure rate of less than 1% per year.
  • Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.
  • Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 7 months after the last dose of investigational product.
  • Two effective forms of non-hormonal contraception (condom with spermicidal jelly, foam suppository or film; diaphragm with spermicide; or male condom and diaphragm with spermicide).
  • Note: Oral contraceptives are not allowed.
  • Female patients who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 15 days following the last dose of study drug.
  • A male with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception or abstinence during the study and for at least 7 months after the last dose of investigational product.
  • Patient will be eligible for inclusion in this study only if either affiliated to or a beneficiary of social security insurance.

Who cannot join

  • History of cancer except cancer dating from over two years ago and considered to be cured, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma and stage I uterine cancer.
  • Any approved anti-cancer therapy ≤ 21 days before enrollment. Note: TKIs approved for the treatment of NSCLC must be discontinued ≥ 7 days prior to the first study treatment on Cycle 1, Day 1. (The baseline scan must be completed after discontinuation of TKIs).
  • Patients with concomitant EGFR, ALK, ROS1, MET, BRAF and KRAS mutation. Other molecular co-alterations should be discussed with IFCT before patient's enrollment.
  • Previous treatment with an anti-HER2 agent.
  • Any other investigational therapy ≤ 28 days before inclusion
  • Previous irradiation <14 days before enrollment.
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  • Brain metastases that are symptomatic, or require any radiation, surgery, or corticosteroid therapy to control symptoms from brain metastases within 4 weeks before enrollment. Asymptomatic brain metastases with a fixed dose of steroids for at least 2 weeks are eligible.
  • Carcinomatous meningitis
  • History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab, pertuzumab or docetaxel or murine proteins or one of the excipients
  • Pregnancy and breast-feeding
  • Any evidence of severe or uncontrolled systemic disease. (E.g. unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) or other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study.
  • Evidence of active pneumonitis during screening
  • Current unstable ventricular arrhythmia requiring treatment, history of symptomatic congestive heart failure (CHF; New York Heart Association [NYHA] Classes II-IV) and history of myocardial infarction or unstable angina within 6 months before enrollment.
  • Unresolved toxicity grade > 2 from previous anti-tumor treatments

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

France18 sites

  • CHU Besançon

    Besançon

  • CHU de Bordeaux

    Bordeaux

  • Caen - CHU Côte de Nacre

    Caen, 14000

  • Clermont-Ferrand - CHU

    Clermont-Ferrand

  • CHI Créteil

    Créteil

  • CHRU Grenoble

    Grenoble

  • Centre Hospitalier - Pneumologie

    Le Mans, 72000

  • Lyon - URCOT

    Lyon

  • Hôpital Nord APHM

    Marseille

  • Montpellier - CHRU

    Montpellier, 34295

  • CHU de Nantes

    Nantes

  • Nice CLCC

    Nice

  • AP-HP Hopital Tenon - Pneumologie

    Paris, 75020

  • AP-HP Hôpital Bichat

    Paris

  • Rennes - CHU

    Rennes, 35033

  • CHU Strasbourg

    Strasbourg

  • CHU Toulouse

    Toulouse

  • Gustave Roussy

    Villejuif

Other trials in France

About this study

Official title: Phase II Trial of Trastuzumab in Combination With Pertuzumab in Pretreated Patients With Non-small Cell Lung Cancer (NSCLC) Harboring a Her2 Mutation and Receiving Docetaxel

HER2 (erbB-2/neu) is a member of the erbB receptor tyrosine kinase family. ERBB2 gene which encodes human epidermal growth factor 2 (HER2) is a major proliferative driver activating downstream signaling through PI3K-AKT and MEK-ERK. HER2 overexpression or gene amplification is associated with sensitivity to trastuzumab and lapatinib in breast cancer. Among actual lung cancer biomarker, HER2 remains apart. HER2 involvement is known for a long time but clinical research has been stopped for many years since the first clinical trials in unselected patients were negative. Recently trastuzumab + pertuzumab + docetaxel has been tested for first-line treatment of HER2-positive metastatic breast cancer (CLEOPATRA trial). Analysis of the primary end point showed that patients who received pertuzumab, trastuzumab, and docetaxel (pertuzumab group) had a significantly longer median progression-free survival, as assessed by independent reviewers an did those who received placebo, trastuzumab, and docetaxel (control group) (hazard ratio favoring the pertuzumab group, 0.62). There is thus a strong rational for treating HER2 mutated lung cancer patient with these drugs.

Being tested
pertuzumab + trastuzumab + docetaxel
Keywords
IFCT, NSCLC, HER2
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • pertuzumab + trastuzumab + docetaxelDrug

    Cycle 1 : D1 : pertuzumab 840 mg, D2 : trastuzumab 8 mg/kg + docetaxel 75 mg/m² Subsequent cycle : D1 : pertuzumab 420 mg + trastuzumab 6 mg/kg + docetaxel 75 mg/m²

Study groups in NCT03845270
Study groupRoleWhat they receive
pertuzumab + trastuzumab + docetaxelExperimentalCycle 1 : D1 : pertuzumab 840 mg, D2 : trastuzumab 8 mg/kg + docetaxel 75 mg/m² Subsequent cycle : D1 : pertuzumab 420 mg + trastuzumab 6 mg/kg + docetaxel 75 mg/m²
Receives: Drug: pertuzumab + trastuzumab + docetaxel

What is being measured

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

  1. Overall Response

    Proportion of patients with a confirmed complete response or partial response according to RECIST version 1.1

    Measured: [Time Frame: About 24 months]

Secondary outcomes (6)

  1. Objective Response Rate

    Percentage of patient with objective response rate with RECIST 1.1 as assessed by radiology review committee

    Measured: 6 weeks

  2. Overall Survival

    Time from enrollment until death due to any cause

    Measured: About 24 months

  3. Progression-free survival

    Time from enrollment to first observation of progression (according to RECIST v1.1) or date of death (from any cause)

    Measured: About 24 months

  4. Duration of response

    Time from documentation of tumor response to disease progression.

    Measured: About 24 months

  5. Objective Response Rate

    Percentage of patient with objective response rate with RECIST 1.1 as assessed by investigators

    Measured: 6 weeks (confirmation needed at least after 4 weeks)

  6. Incidence, type and severity of non-serious and serious adverse event

    Measured: About 24 months

Timeline

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

  1. First posted19 Feb 2019
  2. Study start17 May 2019
  3. Primary completion1 Feb 2021
  4. Study completion18 Dec 2023

Resources

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
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03845270
Sponsor's protocol ID
IFCT-1703
Acronym
R2D2
Status last verified
Dec 2023
First submitted
14 Feb 2019
Last updated
19 Dec 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Mazieres J, Lafitte C, Ricordel C, Greillier L, Negre E, Zalcman G, Domblides C, Madelaine J, Bennouna J, Mascaux C, Moro-Sibilot D, Pinquie F, Cortot AB, Otto J, Cadranel J, Langlais A, Morin F, Westeel V, Besse B. Combination of Trastuzumab, Pertuzumab, and Docetaxel in Patients With Advanced Non-Small-Cell Lung Cancer Harboring HER2 Mutations: Results From the IFCT-1703 R2D2 Trial. J Clin Oncol. 2022 Mar 1;40(7):719-728. doi: 10.1200/JCO.21.01455. Epub 2022 Jan 24.

    PubMed 35073148

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing pertuzumab + trastuzumab + docetaxel in people with Non Small Cell Lung Cancer Metastatic and Non Small Cell Lung Cancer Stage III, run by Intergroupe Francophone de Cancerologie Thoracique at 18 sites in France.

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 31 inclusion and 14 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 19 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in France. 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?

Overall Response (time frame: [Time Frame: About 24 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 NCT03845270, which also lists 1 linked publication.

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 19 Dec 2023.

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