Clinical Trial of the Safety and Effectiveness of CHR-2797 With Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer

NCT00522938 | Terminated Phase 1 DMC

• 1 other identifier: CHR-2797-005
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 7

Brief Summary

This is an open-label, multicenter, multiple-dose, Phase I-II study of CHR-2797 co-administered with erlotinib in patients with histologically or pathologically confirmed Stage IIIB (with pleural effusion), Stage IV, or recurrent metastatic NSCLC. Throughout this protocol, "study medication" includes both CHR-2797 and erlotinib. This study will involve 2 distinct study phases. Study Phase A will assess safety and determine the MTD of the combination of CHR-2797 and erlotinib. In addition, PK profiles for the combination of CHR-2797 and erlotinib will be evaluated. In Study Phase B, the dose chosen based on the maximum tolerated dose established in Study Phase A will be administered in a single-arm treatment design in order to evaluate the efficacy of co-administration of CHR-2797 and erlotinib.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Lung; Cancer; Non-small; Lung Cancer; NSCLC; erlotinib; oral; Locally Advanced Non-small Cell Lung Cancer; Metastatic Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Study Phase A- To determine the safety, tolerability, and maximum tolerated dose (MTD) of CHR-2797 when co-administered with erlotinib

  end of study

• Study Phase B- To determine the objective tumor response rate to CHR-2797 and erlotinib when co-administered to patients with histologically and/or pathologically confirmed Stage IIIB, Stage IV, or recurrent metastatic non-small cell lung cancer (NSCLC)

  End of study

Secondary Outcomes (3)

• Study Phase A- To determine the pharmacokinetic (PK) profiles of CHR-2797 and erlotinib when co-administered

  End of study

• Study Phase B- To further evaluate the efficacy of the combination of CHR-2797 and erlotinib in patients with locally advanced or metastatic non small cell lung cancer (NSCLC)

  End of study

• Study Phase B- To determine the safety and tolerability of CHR-2797 and erlotinib when co administered. To determine the trough levels of CHR-2797 and erlotinib after co-administration for 28 days

  End of study

Interventions

CHR-2797 (tosedostat) DRUG

Once daily, oral ingestion of CHR-2797 capsules(PhaseI: 120mg, 160mg or 200mg depending on cohort or Phase II: recommended dose) capsules until progressive disease or withdrawal from the study

erlotinib DRUG

Once daily, oral ingestion of erlotinib tablets 150mg tablets until progressive disease or withdrawal from the study. Per protocol, the Investigator may reduce the dose of erlotinib or cease treatment with erlotinib(per label) with Sponsor approval.

Also known as: Tarceva

Eligibility Criteria

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

You may qualify if:

• Histologically and/or pathologically confirmed NSCLC (cytologic specimens obtained by brushing, washing, or needle aspiration of a defined lesion are acceptable). This includes the histologic subtypes of squamous cell, adeno, large cell, anaplastic cell, bronchioalveolar carcinoma, and NSCLC not otherwise specified (NOS). Note that tumors with the presence of small cell anaplastic elements are not eligible
• NSCLC with documentation of Stage IIIB (with pleural effusion), or Stage IV, or recurrent metastatic disease based on current TNM classification
• Disease progression or relapse following failure of platinum-based chemotherapy
• For Study Phase A, patients are not required to have measurable disease (according to RECIST criteria) for enrollment. For patients in Study Phase B, patients must have measurable disease according to RECIST, defined by at least 1 lesion that can be accurately measured. All other lesions (e.g., pleural effusions) including small lesions (\<1 cm×1 cm by spiral CT scan) are considered non-measurable for the purposes of this study. Baseline tumor measurements are to be completed as close as possible to, but no longer than 14 days before the start of study treatment
• Prior radiation to the measurable site(s) of disease is not allowed, unless disease progression has been documented at that site since the radiotherapy. Patients who have had extensive radiotherapy are also excluded, because of the associated myelosuppressive effect
• Prior surgery is allowed, provided it was completed at least 4 weeks prior to enrollment and the patient has recovered from surgery.
• No known prior primary brain, metastatic brain, or meningeal tumors or clinical signs or symptoms of brain metastases
• Able to understand and willing to sign an informed consent document
• Age ≥18 years
• Predicted life expectancy \>3 months
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤2
• Laboratory values within the normal or reasonable ranges and, specifically,adequate bone marrow, hepatic, and renal function including the following:
• Hemoglobin \>10 g/dL, absolute neutrophil count (ANC)\>1.5×109/L, platelets ≥100×109/L
• Total bilirubin ≤1.5× upper limit normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5×ULN or \<5×ULN in patients with documented liver metastases

You may not qualify if:

• Excluded therapies:
• Concurrent anti-cancer therapy
• Treatment with cytotoxic agents within the last 3 or 4 weeks, depending on the usual frequency of administration of the regimen, or within the last 6 weeks for agents such as mitomycin. Patients must have had resolution of acute treatment-related toxicities to baseline or National Cancer Institute Common Toxicity Criteria (NCI-CTC) Grade \<1, with the exception of alopecia
• Therapy within the last 28 days or while on study with another investigational drug
• Use of biological response modifiers, such as granulocyte-colony stimulating factor (G-CSF) or erythropoietin, within 28 days of enrollment
• Prior therapy with an epidermal growth factor receptor (EGFR) inhibitor
• Radiation to the site(s) of measurable disease, unless disease progression has been documented at that site since the radiotherapy.
• Need for palliative radiotherapy of indicator lesions
• Treatment with known strong CYP3A4 inhibitors, for example '- azole antifungals, protease inhibitors, erythromycin, clarithromycin within 2 weeks of enrollment or at any time during the study
• Treatment with strong CYP3A4 inducers such as rifampicin, rifabutin or rifapentine within 2 weeks of enrollment or at any time during the study
• Warfarin or doses of coumadin (or equivalent) that are higher than 1mg/day
• Excluded medical conditions:
• Current hematological malignancy
• Gastro-intestinal abnormalities including:
• Inability to take oral medication

Sponsors & Collaborators

• Chroma Therapeutics: lead

Study Sites (7)

Tower Cancer Research Foundation

Beverly Hills, California, 90210, United States

Location

Medical Oncology Care Associates

Orange, California, 92868, United States

Location

Oncology Associates of West Kentucky

Paducah, Kentucky, 42003, United States

Location

Richmond University Medical Center

Staten Island, New York, 10310, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Clinworks Research Center

Charlotte, North Carolina, 28207, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28070, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms; Lung Neoplasms

Interventions

tosedostat; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2007
• First Posted: August 30, 2007
• Study Start: December 1, 2007
• Primary Completion: February 1, 2008
• Study Completion: April 1, 2008
• Last Updated: June 28, 2012

Record last verified: 2012-02

Locations

US (7)