The 'MADe IT' Clinical Trial: Molecular Analyses Directed Individualized Therapy for Advanced Non-Small Cell Lung Cancer

NCT00215930 | Completed Phase 2 Results DMC

• 1 other identifier: MCC-13208
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

The standard treatment for non-small cell lung cancer, stage IV or IIIB malignant pleural effusion is chemotherapy. The decision to use a regimen is currently determined by toxicity or by physician's preference. In this protocol, the treatment regimen will be assigned based on the patients' tumor molecular profile. A tumor molecular profile analysis will allow the physician to define a specific molecular portrait that shows the genetic basis of the tumor. This analysis results in a detailed report that will determine which chemotherapy will be assigned to the patient.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

malignant pleural effusion

Outcome Measures

Primary Outcomes (1)

• Best Disease Response After a Maximum of Six Cycles.

  Determine the number of participants for each category of response rates (RR) in newly diagnosed patients with advanced non-small cell lung cancer (NSCLC) who are treated with a chemotherapeutic regimen assigned to them on the basis of expression of the genes ribonucleotide reductase subunit 1 (ERCC1) and excision repair cross-complementing group 1 gene (RRM1) expression. Prior to treatment we measured the level of ERCC1 and RRM1 expression in the patients tumor, on the basis of which the patient would be assigned a specific doublet chemotherapy.

  24 Months

Secondary Outcomes (2)

• Overall Survival (OS)

  24 Months

• Progression Free Survival (PFS)

  24 Months

Study Arms (1)

Double Agent Chemotherapy

EXPERIMENTAL

Molecular Analysis-Directed Chemotherapy Assignment based on gene expression of ERCC1 and RRM1.

Drug: Vinorelbine; Drug: Docetaxel; Drug: Gemcitabine; Drug: Carboplatin

Interventions

Vinorelbine DRUG

Ribonucleotide reductase subunit 1(RRM1)above 16.5 and Excision repair cross-complementing group 1 gene(ERCC1)above 8.7: Treat patients with Docetaxel and Vinorelbine (DV). DV group was treated with vinorelbine (45mg/m2ondays 1 and 15) and docetaxel (60mg/m2ondays 1 and 15) every 28 days.

Also known as: Navelbine

Double Agent Chemotherapy

Docetaxel DRUG

RRM1 below 16.5 and ERCC1 above 8.7: Treat patients with Gemcitabine and Docetaxel (GD). GD group was treated with gemcitabine (1,250 mg/m2 on days 1 and 8) and docetaxel (40 mg/m2 on days 1 and 8) every 21 days. RRM1 above 16.5 and ERCC1 below 8.7: Treat patients with Docetaxel and Carboplatin (DC). DC group was treated with docetaxel (75 mg/m2 on day 1) and carboplatin (AUC 5 on day 1) every 21 days. RRM1 above 16.5 and ERCC1 above 8.7: Treat patients with Docetaxel and Vinorelbine (DV). DV group was treated with vinorelbine (45mg/m2ondays 1 and 15) and docetaxel (60mg/m2ondays 1 and 15) every 28 days.

Also known as: Taxotere

Double Agent Chemotherapy

Gemcitabine DRUG

Ribonucleotide reductase subunit 1(RRM1) below 16.5, and Excision repair cross-complementing group 1 gene(ERCC1) below 8.7: Patients treated with Gemcitabine and Carboplatin (GC). GC group was treated with gemcitabine (1,250 mg/m2 on days 1 and 8) and carboplatin (area under the concentration-time curve \[AUC\] of 5 on day 1) every 21 days. RRM1 below 16.5 and ERCC1 above 8.7: Treat patients with Gemcitabine and Docetaxel (GD). GD group was treated with gemcitabine (1,250 mg/m2 on days 1 and 8) and docetaxel (40 mg/m2 on days 1 and 8) every 21 days.

Also known as: Gemzar

Double Agent Chemotherapy

Carboplatin DRUG

Ribonucleotide reductase subunit 1(RRM1) below 16.5, and Excision repair cross-complementing group 1 gene(ERCC1) below 8.7: Patients treated with Gemcitabine and Carboplatin (GC). GC group was treated with gemcitabine (1,250 mg/m2 on days 1 and 8) and carboplatin (area under the concentration-time curve \[AUC\] of 5 on day 1) every 21 days. RRM1 above 16.5 and ERCC1 below 8.7: Treat patients with Docetaxel and Carboplatin (DC). DC group was treated with docetaxel (75 mg/m2 on day 1) and carboplatin (AUC 5 on day 1) every 21 days.

Also known as: Paraplatin

Double Agent Chemotherapy

Eligibility Criteria

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

You may qualify if:

• histologically confirmed adenocarcinoma, large cell or squamous cell carcinoma NSCLC; as well as be willing to undergo a biopsy to enable customization of chemotherapy; unresectable/ metastatic (stage IV or IIIB malignant pleural effusion) NSCLC;
• male or female, aged \> 18 years;
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;
• adequate bone marrow, hepatic and renal function assessed within 14 days as evidenced by the following:
• absolute neutrophil count \> 1,500/mm3
• platelet count \> 100,000/mm3
• Hemoglobin \> 8gm/dl
• no evidence of myelodysplastic syndrome or abnormal bone marrow reserve;
• creatinine \< 1.5 x upper normal limit(UNL)
• total bilirubin must be within normal limits
• aspartate aminotransferase(AST)Serum glutamic oxaloacetic transaminase(SGOT) and/or alanine aminotranserase (ALT) serum glutamic pyruvic transaminase(SGPT) \< 2×5 x UNL in the presence of a normal alkaline phosphatase;
• alkaline phosphatases \< 4 x UNL in the presence of normal AST and ALT; patients with elevations of both alkaline phosphatase and liver enzymes (AST \& ALT) will be excluded.
• serum calcium \< 1.1 x UNL;
• at least one unidimensionally measurable lesion;
• signed informed consent;

You may not qualify if:

• Pregnant or lactating women
• Prior systemic chemotherapy or immunotherapy for advanced NSCLC, patients may have received neoadjuvant or adjuvant therapy but more than 6 months prior to study entry;
• Prior malignancies, except cured non-melanoma skin cancer, curatively treated in situ carcinoma of the cervix or other cancer curatively treated and with non-evidence of disease for at least 3 years;
• presence of uncontrolled brain or leptomeningeal metastases;
• current peripheral neuropathy and hearing deficit of neural origin, CTCAE v3.0 grade 2 except if due to trauma;
• other serious illness or medical condition, including but not limited to:
• congestive heart disease; prior myocardial infarction within 6 months;
• history of significant neurologic or psychiatric disorders that would inhibit their understanding and giving of informed consent;
• infection requiring I.V. antibiotics and tuberculosis under treatment ongoing at study entry;
• untreated superior vena cava syndrome;
• active peptic ulcer; unstable diabetes mellitus or other contraindication to high dose corticosteroid therapy such as herpes, herpes zoster, cirrhosis;
• hypercalcemia requiring therapy at the time of study entry;
• preexisting clinically significant ascites and/or clinical significant pericardial effusion;
• patients whose lesion(s) are assessable only by radionuclide scan;
• patients with a history of severe hypersensitivity reaction to Taxotere or other drugs formulated with polysorbate 80 must be excluded

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Eli Lilly and Company: collaborator
• Aventis Pharmaceuticals: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Pleural Effusion, Malignant

Interventions

Vinorelbine; Docetaxel; Gemcitabine; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Pleural Neoplasms; Pleural Effusion; Pleural Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes

Results Point of Contact

• Title: Gerald Bepler, M.D., via Moffitt Cancer Center
• Organization: Karmanos Cancer Institute (formerly at Moffitt Cancer Center)

beplerg@karmanos.org

813-745-4398

Study Officials

• Gerold Bepler, MD, PhD

  H. Lee Moffitt Cancer Center & Research Institute (now at Karmanos Cancer Institute)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: September 15, 2005
• First Posted: September 22, 2005
• Study Start: February 1, 2004
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: March 23, 2017
• Results First Posted: February 23, 2011

Record last verified: 2011-03

Locations

US (1)