- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00522938
Clinical Trial of the Safety and Effectiveness of CHR-2797 With Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
A Phase I-II, Multicenter, Open-label Trial of Co-administered CHR-2797 and Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Phase A:
Maximum tolerated dose will be determined during Cycle 1. Tumor assessments will be made after Cycle 2 (56 days), although it is not mandatory for Phase A patients to have measurable disease. Patients who have satisfactory outcomes after Cycle 2 may continue treatment for up to a year with erlotinib 150 mg/day, and the dose of CHR-2797 they received in Study Phase A.
Study Phase B:
Patients will be treated with the dose of CHR-2797 selected in Study Phase A and 150mg/day erlotinib. Patients will receive 2 cycles of treatment (56 days) before efficacy assessment. Patients who have complete response, partial response, or stable disease are eligible to continue the study for up to a year until disease progression or unacceptable toxicity. If a patient has complete response, partial response, or stable disease at the end of the 1-year study period and the Investigator believes that continuation treatment would be beneficial, the patient may continue to be treated at the dose of CHR-2797 under a separate protocol.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Beverly Hills, California, United States, 90210
- Tower Cancer Research Foundation
-
Orange, California, United States, 92868
- Medical Oncology Care Associates
-
-
Kentucky
-
Paducah, Kentucky, United States, 42003
- Oncology Associates of West Kentucky
-
-
New York
-
Bronx, New York, United States, 10467
- Montefiore Medical Center
-
Staten Island, New York, United States, 10310
- Richmond University Medical Center
-
-
North Carolina
-
Charlotte, North Carolina, United States, 28207
- Clinworks Research Center
-
Huntersville, North Carolina, United States, 28070
- Carolina BioOncology Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- Creatinine ≤1.5×ULN or calculated creatinine clearance ≥60 mL/min
- Female patients with reproductive potential must have a negative serum pregnancy test within 72 hours prior to start of study medication. All female patients of childbearing potential, and all male patients, must agree to use a medically acceptable method of contraception or agree to be abstinent throughout the treatment period and for 3 months after discontinuation of treatment. (See Section 4.1for more information.)
- Screening for LVEF >= 55%
Exclusion Criteria:
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
- Requirement for intravenous (IV) alimentation
- Malabsorption syndrome
- Active peptic ulcer disease
- A serious uncontrolled medical disorder or active infection which would impair their ability to receive study treatment
- Known primary brain, metastatic brain, or meningeal tumors, or clinical signs or symptoms of brain metastases
- Second malignancy (except adequately treated basal cell carcinoma of the skin or in-situ carcinoma of the cervix or breast)
- Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
- Uncontrolled hypercalcemia (>NCI-CTC Grade 1)
Significant cardiovascular disease including but not limited to the following:
- History (past or present) of congestive heart failure
- History (past or present) of angina pectoris requiring medication
- History of myocardial infarction with past 12 months
- Presence of clinically significant valvular heart disease
- History (past or present) of arrhythmia requiring treatment
- Presence of conduction defect on Screening ECG
- History (past or present) of uncontrolled hypertension
- Patients with interstitial lung disease
- Major surgery within 4 weeks prior to enrollment
- >20% weight loss in previous 3 months
- Pregnant or lactating women
- Known rapidly deteriorating liver function tests (2×ULN rise in 1 week)
- Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and/or compliance with the requirements of the protocol
- Known or suspected allergy to any study medication used in this study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Study Phase A- To determine the safety, tolerability, and maximum tolerated dose (MTD) of CHR-2797 when co-administered with erlotinib
Time Frame: end of study
|
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)
Time Frame: End of study
|
End of study
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Study Phase A- To determine the pharmacokinetic (PK) profiles of CHR-2797 and erlotinib when co-administered
Time Frame: End of study
|
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)
Time Frame: End of study
|
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
Time Frame: End of study
|
End of study
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Erlotinib Hydrochloride
- Tosedostat
Other Study ID Numbers
- CHR-2797-005
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Carcinoma, Non-Small-Cell Lung
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Bristol-Myers SquibbCompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage I Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung Cancer | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung Carcinoma | Non-Squamous Non-Small...United States
-
National Cancer Institute (NCI)CompletedStage IIIA Non-Small Cell Lung Cancer | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IB Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIA Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIB Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIIA Lung Non-Small Cell Cancer AJCC v7 | Recurrent Lung Non-Small Cell Carcinoma | Stage IIIB Lung Non-Small Cell Cancer AJCC v7 | Stage IA...United States
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
-
M.D. Anderson Cancer CenterActive, not recruitingStage IB Lung Non-Small Cell Carcinoma AJCC v7 | Stage II Lung Non-Small Cell Cancer AJCC v7 | Stage IIA Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIB Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIIA Lung Non-Small Cell Cancer AJCC v7 | Stage I Lung Non-Small Cell Cancer AJCC v7 | Stage...United States
-
National Cancer Institute (NCI)Active, not recruitingLung Non-Squamous Non-Small Cell Carcinoma | Stage IB Lung Non-Small Cell Carcinoma AJCC v7 | Stage II Lung Non-Small Cell Cancer AJCC v7 | Stage IIA Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIB Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIIA Lung Non-Small Cell Cancer AJCC v7United States, Puerto Rico
-
National Cancer Institute (NCI)Active, not recruitingStage IIIA Lung Non-Small Cell Cancer AJCC v7 | Advanced Lung Non-Squamous Non-Small Cell Carcinoma | Metastatic Lung Non-Squamous Non-Small Cell Carcinoma | Stage IIIB Lung Non-Small Cell Cancer AJCC v7 | Stage IV Lung Non-Small Cell Cancer AJCC v7 | Stage III Lung Non-Small Cell Cancer AJCC...United States
-
University of Southern CaliforniaNational Cancer Institute (NCI); Society of Thoracic RadiologyActive, not recruitingStage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIIB Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
Clinical Trials on CHR-2797 (tosedostat)
-
Chroma TherapeuticsCompletedAcute Myeloid Leukemia | Multiple Myeloma | Myelodysplastic SyndromeUnited Kingdom
-
Chroma TherapeuticsInstitute of Cancer Research, United KingdomCompletedAdvanced Solid Tumors
-
Chroma TherapeuticsUnknownAcute Myeloid LeukemiaUnited States
-
Weill Medical College of Cornell UniversityCTI BioPharmaCompletedMyelodysplastic SyndromeUnited States
-
Chroma TherapeuticsCompleted
-
Chroma TherapeuticsQuintiles, Inc.CompletedAcute Myeloid Leukemia | AMLUnited States, Canada, Netherlands
-
CTI BioPharmaChroma TherapeuticsCompleted
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedAdult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Previously Treated Myelodysplastic Syndromes | Secondary Myelodysplastic Syndromes | Adult Acute Myeloid Leukemia... and other conditionsUnited States
-
GlaxoSmithKlineTerminatedArthritis, RheumatoidUnited Kingdom
-
Chroma TherapeuticsCompletedLymphoid Malignancies | Hematological DiseaseFrance, Belgium, Netherlands