A Kadcyla (also known as trastuzumab emtansine or T-DM1) study in patients with HER2-positive lung cancer after chemotherapy treatment

Phase 1

• Conditions: HER2 IHC-Positive (IHC 2 + or IHC 3 +), Locally Advanced or Metastatic Non-Small Cell Lung Cancer; MedDRA version: 20.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-001237-83-PL
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-10-27
• Last Update Posted: 12 November 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

- Age >= 18 years
- Histologically or cytologically documented diagnosis of Stage IIIB not amenable to radical treatment or Stage IV NSCLC; pathological characterization must determine the non-squamous or squamous histological subtype as well as adenocarcinoma subtype classification.
- HER2 status of IHC 2+ or 3+ as determined by a Sponsor-designated central laboratory
- Prior treatment with at least one regimen of platinum-based (cisplatin or carboplatin) chemotherapy in the locally advanced or metastatic setting/recurrent NSCLC with documented disease progression by investigator assessment
- Patients with a known ALK fusion oncogene (must be documented in the patient's chart) must have also experienced disease progression or intolerance with a first-line ALK Tyrosine Kinase Inhibitor (TKI) approved for the treatment of ALK fusion oncogene NSCLC (e.g., crizotinib). Disease progression or intolerance must be documented
- Patients with a known mutation in the EGFR gene (must be documented in the patient's chart) must have also experienced disease progression or intolerance with an EGFR TKI approved for the treatment of EGFR-mutant NSCLC (e.g., gefitinib, erlotinib, afatinib). Disease progression or intolerance must be documented.
- Measurable disease determined as per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1
- Life expectancy >= 12 weeks
- Adequate organ function
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- LVEF >= 50% by either echocardiogram (ECHO) or or multiple-gated acquisition (MUGA)
- Use of highly effective contraception
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28

Exclusion Criteria

Cancer-Related Criteria
- Any approved anti-cancer therapy <= 21 days (including chemotherapy or hormonal therapy) before the first study treatment; the following exceptions are allowed: (1) 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 computed tomography scan must be completed after discontinuation of TKIs); (2) Hormone-replacement therapy or oral contraceptives; (3) Anti-emetics, GCS-F, prophylactic antibiotics are allowed according to local standards
- Investigational therapy participation in another clinical study with therapeutic intent <= 21 days before first study treatment
- Previous irradiation is permitted if >= 14 days since the last fraction of radiotherapy have elapsed before the first study treatment on Day 1 of Cycle 1 as long as a sufficient number of target lesions remain to allow for measurable disease as per RECIST v1.1.
- Patients who have untreated brain metastases or are symptomatic; patients with treated brain metastases must have discontinued corticosteroid therapy and not have any neurological symptoms
- History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins or any excipient of the product
- History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin > 500 miligrams per meter square (mg/m2); Epirubicin > 900 mg/m2; Mitoxantrone > 120 mg/m2. If another anthracycline, or more than one anthracycline, has been used, the cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin.
- Current peripheral neuropathy of Grade >= 3 per the National Cancer Institute Common Toxicity Criteria for Adverse Events v. 4.0
- History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those mentioned above.

Cardiopulmonary Function Criteria
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- Severe dyspnea at rest due to complications of advanced malignancy or requiring current continuous oxygen therapy
- Clinical history of active hemoptysis
- Evidence of pneumonitis during screening
- Current unstable ventricular arrhythmia requiring treatment
- History of symptomatic congestive heart failure (CHF; New York Heart Association [NYHA] Classes II-IV)
- History of myocardial infarction or unstable angina within 6 months of enrollment
- History of a decrease in LVEF to < 50%

General Criteria
- Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease)
- Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of the need for major surgery during the course of study treatment
- Current pregnancy or lactation
- Current known active infection with HIV, hepatitis B, or hepatitis C virus

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified