Randomized Phase III Multicenter Trial of RRM1 & ERCC1 Directed Customized Chemotherapy versus Standard of Care for 1st Line Treatment of Patients with Advanced Non-Small-Cell Lung Cancer - MADeIT

Status

Not yet recruiting

Phases

Unknown

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2008-000617-30-DE

Enrollment

267

Registered

2008-09-26

Start date

2008-09-25

Completion date

Unknown

Last updated

2012-08-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Patients with untreated advanced stage NSCLC. 2:1 randomization to experimental (A) or standard arm (B). In arm A, treatment of dual-agent chemotherapy will be selected based on RRM1 and ERCC1 expression at the protein level and will consist of gemcitabine and carboplatin (GC), docetaxel and carboplatin (DC), gemcitabine and docetaxel (GD), or docetaxel and vinorelbine (DV). In arm B, treatment of dual-agent chemotherapy will be gemcitabine/carboplatin (GC) (standard of care). MedDRA versio

Interventions

Trade Name: Taxotere Product Name: Docetaxel Pharmaceutical Form: Concentrate and solvent for solution for injection INN or Proposed INN: Docetaxel CAS Number: 114977-28-5 Other descriptive name: DOCE

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Histologically confirmed NSCLC of adenocarcinoma, squamous cell carcinoma, large cell carcinoma, or NSCLC not otherwise specified (NOS). Patients with suspected NSCLC may enroll prior to the diagnostic biopsy in order to obtain both the diagnostic and molecular analysis-required specimen during the same procedure. - Willing to undergo a biopsy to enable customization of chemotherapy - Stage IV or IIIB (malignant pleural effusion) NSCLC - Measurable or evaluable disease by RECIST (Therasse et al, JNCI 2000) - Age >= 18 years - Previous chemotherapy is allowed if the last dose was administered equal to or greater than 12 months ago. This chemotherapy must have been given in an adjuvant or neoadjuvant mode prior to or after a complete surgical resection (R0 resection) for a NSCLC. - Patients with stable brain metastases will be allowed to enroll. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: - Pregnant or lactating women - Prior systemic chemotherapy or immunotherapy for advanced NSCLC. - Prior malignancies, except: cured non-melanoma skin cancer; curatively treated in situ carcinoma of the cervix; any other curatively treated malignancy with no evidence of disease recurrence for at least 3 years - peripheral neuropathy or hearing loss of neural origin equal to or greater than grade 2 by CTCAE v3.0 except if due to trauma - patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80

Design outcomes

Primary

Measure	Time frame
Main Objective: The primary objective is to evaluate if chemotherapy selection based on tumoral RRM1 and ERCC1 expression results in superior outcome in patients with untreated, advanced NSCLC compared to standard of care treatment with gemcitabine and carboplatin. - primary endpoint is PFS at 6 months (determined from the date of randomization) - secondary endpoints are OS and response rates to treatment. ;Secondary Objective: - to determine the feasibility of treatment selection based on pharmacogenomic parameters - to describe the toxicity in patients treated with and without assignment of chemotherapy based on gene expression. Tertiary objectives: pharmacogenomic objectives ;Primary end point(s): Progression free survival: The primary endpoint is PFS at 6 months (determined from the date of randomization). The anticipated 6-month PFS in arm B is 38% (median PFS 0 of 4.3 months), and the goal in the experimental arm is to achieve a 33% improvement to 50% at 6 months (median PFS of 6.0 months). Overall survival and response rates to treatment: The secondary endpoints are OS (determined from the date of randomization) and response rates to treatment. The anticipated median OS in arm B is approximately 8.0 months, and we anticipate to achieve a 50% improvement to 12.0 months. Second-line treatments given to patients will be recorded as they may impact substantially on OS. Patients in arm B will not be allowed second-line treatment selection based on tumoral RRM1 and ERCC1 expression (the tumoral RRM1 and ERCC1 expression values will not be made available to the care providers). Response to treatment will be determined according to RECIST. The anticipated RR in arm B is approximately 25%, and the goal in the experimental arm is to achieve a 50% improvement to 37.5%.	—

Measure

Time frame

Main Objective: The primary objective is to evaluate if chemotherapy selection based on tumoral RRM1 and ERCC1 expression results in superior outcome in patients with untreated, advanced NSCLC compared to standard of care treatment with gemcitabine and carboplatin. - primary endpoint is PFS at 6 months (determined from the date of randomization) - secondary endpoints are OS and response rates to treatment. ;Secondary Objective: - to determine the feasibility of treatment selection based on pharmacogenomic parameters - to describe the toxicity in patients treated with and without assignment of chemotherapy based on gene expression. Tertiary objectives: pharmacogenomic objectives ;Primary end point(s): Progression free survival: The primary endpoint is PFS at 6 months (determined from the date of randomization). The anticipated 6-month PFS in arm B is 38% (median PFS 0 of 4.3 months), and the goal in the experimental arm is to achieve a 33% improvement to 50% at 6 months (median PFS of 6.0 months). Overall survival and response rates to treatment: The secondary endpoints are OS (determined from the date of randomization) and response rates to treatment. The anticipated median OS in arm B is approximately 8.0 months, and we anticipate to achieve a 50% improvement to 12.0 months. Second-line treatments given to patients will be recorded as they may impact substantially on OS. Patients in arm B will not be allowed second-line treatment selection based on tumoral RRM1 and ERCC1 expression (the tumoral RRM1 and ERCC1 expression values will not be made available to the care providers). Response to treatment will be determined according to RECIST. The anticipated RR in arm B is approximately 25%, and the goal in the experimental arm is to achieve a 50% improvement to 37.5%.

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Countries

Germany

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026