Phase III of RRM1 & ERCC1 Directed Customized Chemotherapy for the Treatment of Patients With NSCLC

NCT00499109 | Completed Phase 3 Results

• 4 other identifiers: MCC-15005105372IST 12223CA129343
• Study Type: interventional
• Target: 275
• Locations: 3 countries
• Sites: 9

Brief Summary

This is a clinical research study to evaluate if chemotherapy in the experimental arm (E) results in a better outcome compared to patients in the standard of care arm (C). 2:1 randomization to experimental arm (E) or standard arm (C). In arm E, treatment of dual-agent chemotherapy will be selected based on RRM1 and ERCC1 expression at the protein level. In arm C, treatment of dual-agent chemotherapy will be gemcitabine/carboplatin, i.e., standard of care.

Conditions

Non-Small Cell Lung Cancer

Keywords

RRM1; ERCC1; Customized Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. The data of first documented disease progression or death, as defined by Response Evaluation Criteria In Solid Tumors (RECIST), was recorded, and the time interval from randomization to that date was calculated for each patient and used to generate Kaplan-Meier survival estimates and to calculate the PFS at 6 months.

  6 months

Secondary Outcomes (2)

• Overall Survival (OS)

  12 months

• Response Rate (RR)

  6 months

Study Arms (2)

E. Dual Agent Chemotherapy

EXPERIMENTAL

Experimental Arm E. Patients received treatment according to gene expression strata with four doublet regimens. Low ERCC1 and Low RRM1 Group - Gemcitabine (G) and Carboplatin (Cb): GCb Group. Low RRM1 and High ERCC1 Group - Gemcitabine (G) and Docetaxel (D): GD Group. High RRM1 and Low ERCC1 Group - Docetaxel (D) and Carboplatin (Cb): DCb Group. High ERCC1 and High RRM1 Group - Vinorelbine (V) and Docetaxel (D): DV Group.

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

C. Standard of Care Control Arm

ACTIVE COMPARATOR

Control Arm C: Gemcitabine and Carboplatin (GCb). All patients in arm C were treated with GCb regardless of gene expression levels. Patients received up to 6 cycles, and no maintenance therapy was allowed.

Drug: Carboplatin; Drug: Gemcitabine

Interventions

Docetaxel DRUG

GD Group: 40 mg/m\^2 on days 1 and 8, every 21 days DCb Group: 75 mg/m\^2 on day 1 DV Group: 50 mg/m\^2 on days 1 and 15, every 28 days

Also known as: Taxotere

E. Dual Agent Chemotherapy

Vinorelbine DRUG

DV Group: 35 mg/m\^2 on days 1 and 15

Also known as: anti-cancer chemotherapy drug

E. Dual Agent Chemotherapy

Carboplatin DRUG

GCb Group: Area under the curve (AUC) 5 on day 1, every 21 days DCb Group: AUC 6 on day 1, every 21 days Control Arm: Patients received up to 6 cycles, and no maintenance therapy was allowed.

Also known as: Paraplatin

C. Standard of Care Control Arm; E. Dual Agent Chemotherapy

Gemcitabine DRUG

GCb Group: 1,250 mg/m\^2 on days 1 and 8 GD Group: 1,250 mg/m\^2 on days 1 and 8 Control Arm: Patients received up to 6 cycles, and no maintenance therapy was allowed.

Also known as: Gemzar

C. Standard of Care Control Arm; E. Dual Agent Chemotherapy

Eligibility Criteria

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

You may not qualify if:

• Willing to undergo biopsy to enable customization of chemotherapy
• Stage IV or IIIB (malignant pleural effusion) NSCLC
• Measurable or evaluable disease by Response Evaluation Criteria In Solid Tumors (RECIST)
• Performance status 0 or 1 by Eastern Cooperative Oncology Group (ECOG) criteria
• Adequate bone marrow function as evidenced by the following (assessed within 14 days of starting treatment): Absolute neutrophil count \>= 1,500/mm³, Platelet count \>= 100,000/mm³, Hemoglobin \>= 8.0 gm/dL
• Prothrombin time (PT) and activated prothrombin time with thromboplastin and kaolin (APTT) within normal laboratory ranges
• Serum creatinine \<= 1.5 x upper limit of normal (ULN) assessed within 14 days of starting treatment
• Adequate liver function as evidenced by the following (assessed within 14 days of starting treatment): Total bilirubin must be within normal limits; aspartic transaminase (AST) and alanine transaminase (ALT) \<= 2.5 x ULN with a normal alkaline phosphatases; alkaline phosphatases \<= 4 x upper limit of normal with normal AST and ALT; patients with elevations of alk phos and AST and/or ALT will be excluded
• Serum calcium \<= 1.1 x ULN
• Signed informed consent document
• Women of childbearing potential must have a negative pregnancy test. Men with partners in the childbearing age group and women of childbearing potential must use effective contraception while on treatment and for 6 months thereafter.
• Previous surgery for NSCLC (more that 30 days before study entry)
• Previous radiotherapy (RT) is allowed if: the time between completion of RT and initiation of chemotherapy is at least 7 days; the patient has fully recovered from all toxic effects; at least one target lesion or evaluable disease is outside the radiation field
• Previous chemotherapy 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. Stable brain metastases being defined as no progression of brain metastases 28 days after conclusion of definitive treatment as documented by a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain. Patients with incidentally discovered asymptomatic brain metastases may be enrolled and treated with chemotherapy without prior brain irradiation if deemed feasible by the treating physician.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Sanofi: collaborator

Study Sites (9)

Center for Cancer Care & Research/Watson

Lakeland, Florida, 33805, United States

Location

Leesburg Regional Medical Center

Leesburg, Florida, 34748, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Johns Hopkins Sidney Kimmell Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Southeast Nebraska Cancer Center

Lincoln, Nebraska, 68510-2496, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2947, United States

Location

Klinik Loewenstein

Löwenstein, 74245, Germany

Location

Ponce School of Medicine

Ponce, 00716, Puerto Rico

Location

Related Publications (1)

• Bepler G, Williams C, Schell MJ, Chen W, Zheng Z, Simon G, Gadgeel S, Zhao X, Schreiber F, Brahmer J, Chiappori A, Tanvetyanon T, Pinder-Schenck M, Gray J, Haura E, Antonia S, Fischer JR. Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2013 Jul 1;31(19):2404-12. doi: 10.1200/JCO.2012.46.9783. Epub 2013 May 20.

  PMID: 23690416 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Docetaxel; Vinorelbine; Carboplatin; Gemcitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Charles C. Williams, M.D., Study Chair
• Organization: H. Lee Moffitt Cancer Center and Research Institute

charles.williams@moffitt.org

813-745-7282

Study Officials

• Charles Williams, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2007
• First Posted: July 11, 2007
• Study Start: May 1, 2007
• Primary Completion: April 1, 2013
• Study Completion: November 1, 2013
• Last Updated: July 9, 2014
• Results First Posted: March 26, 2014

Record last verified: 2014-06

Locations

DE (1); PR (1); US (7)