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A Phase 2 Exploratory Study of Erlotinib and SNDX-275 in Patients With Non-small Cell Lung Carcinoma Who Are Progressing on Erlotinib

This study has been completed.
Sponsor:
Information provided by:
Syndax Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00750698
First received: September 8, 2008
Last updated: March 17, 2011
Last verified: February 2010
  Purpose

Preclinical studies have shown that SNDX-275 is able to reactivate the expression of EGFR, E-cadherin and ErbB3 expression. The combination of SNDX-275 with erlotinib (an EGFRi) in patients who are progressing on erlotinib will show measurable activity as evidenced by the disease control rate and with an acceptable safety profile.


Condition Intervention Phase
Non Small Cell Lung Cancer
Drug: SNDX-275
Drug: erlotinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Exploratory Study of Erlotinib and SNDX-275 in Patients With Non-small Cell Lung Carcinoma Who Are Progressing on Erlotinib

Resource links provided by NLM:


Further study details as provided by Syndax Pharmaceuticals:

Primary Outcome Measures:
  • Disease control rate (complete response, partial response, or stable disease for at least 3 months) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival rate at 2 months [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Progression-free survival rate at 4 months [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: August 2008
Study Completion Date: June 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
"Erlotinib-responsive" patients are those who progressed following either a complete or partial response to erlotinib or a period of stable disease lasting at least 3 months.
Drug: SNDX-275
SNDX-275 (10 mg fixed dose PO Q2W) on days 1 and 15 of a 28-day cycle for up to 6 cycles
Other Name: entinostat
Drug: erlotinib
erlotinib (150 mg PO QD) for up to six (6) 28-day cycles
Other Name: Tarceva
Experimental: 2
"Erlotinib-nonresponsive" patients are those who either progressed immediately during treatment with erlotinib (i.e. after at least 1 full cycle of erlotinib treatment) or had an objective response or period of stable disease lasting less than 3 months.
Drug: SNDX-275
SNDX-275 (10 mg fixed dose PO Q2W) on days 1 and 15 of a 28-day cycle for up to 6 cycles
Other Name: entinostat
Drug: erlotinib
erlotinib (150 mg PO QD) for up to six (6) 28-day cycles
Other Name: Tarceva

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION:

  1. Cytologically or histologically confirmed NSCLC of stage IIIb (pleural effusion) or IV
  2. Disease is progressing (either no response to treatment or subsequent relapse after an objective response) on erlotinib treatment, based on at least 2 scans (the last being within 4 weeks of study enrollment and can serve as the baseline scan for the patient's screening into the study )
  3. Recovered from any toxicity associated with the most recent cancer treatment (no greater than grade 1 toxicity on CTCAE scale or to prior baseline condition)
  4. At least 1 measurable lesion ≥ 20mm by conventional CT scan or ≥ 10mm by spiral CT scan
  5. ECOG performance score of 0, 1, or 2 and life expectancy of at least 3 months
  6. Paraffin-embedded tumor specimen available for correlative studies
  7. Male or female over 18 years of age
  8. Hemoglobin ≥ 9.0 g/dL; platelets ≥ 75 x 10⁹/L; ANC ≥ 1.0 x 10⁹/L without the use of hematopoietic growth factors
  9. Coagulation tests within the normal range
  10. Bilirubin and creatinine less than 2 times the upper limit of normal for the institution
  11. AST and ALT less than 3 times the upper limit of normal for the institution
  12. Potassium, magnesium and phosphorus within the normal range for the institution (supplementation is permissible)
  13. Willing to use accepted and effective methods of contraception during the study (both men and women as appropriate) and for 3 months after the last dose of SNDX-275
  14. Patient or legally acceptable representative has granted written informed consent before any study-specific procedure (including special screening tests) is performed

EXCLUSION:

  1. Prior stem cell transplant
  2. Symptomatic CNS involvement
  3. Prior treatment with an HDAC inhibitor
  4. Concurrent anticancer therapy, with the exception of radiotherapy for a non-target study lesion
  5. Currently taking medication(s) on the prohibited medication list
  6. Systemic chemotherapy or treatment with an investigational agent within 28 days before enrollment
  7. Current use of valproic acid
  8. Untreated or unstable brain metastases, or taken steroids for this condition within 4 weeks of study drug administration
  9. Currently active second malignancy, or any malignancy within the last 5 years other than cured basal or squamous cell skin carcinoma, cervical carcinoma in situ, or superficial bladder cancer
  10. Inability to swallow oral medications or a gastrointestinal malabsorption condition
  11. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known HIV infection, or active hepatitis B or C infection
  12. Abnormal cardiac function as defined as clinically significant findings on ECG (multifocal PVCs, ST-T wave changes consistent with myocardial infarction or acute ischemia, QTc greater than 500 milliseconds), tachycardia, or left ventricular ejection fraction less than 40% on MUGA scan
  13. Another serious or uncontrolled medical condition within 3 months of enrollment such as hypertension, diabetes mellitus, or suppressed immune system
  14. Known hypersensitivity to benzamides
  15. Morbid obesity
  16. Women who are currently pregnant or breast-feeding
  17. Patient is currently enrolled in (or completed within 28 days) another investigational drug study
  18. Patient unavailable for on-study or follow-up assessments
  19. Patient has any kind of medical, psychiatric, or behavioral disorder that places the patient at increased risk for study participation or compromises the ability of the patient to give written informed consent and/or to comply with study procedures and requirements
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00750698

Locations
United States, California
City of Hope
Duarte, California, United States
University of California San Diego
La Jolla, California, United States
Sharp Memorial Hospital
San Diego, California, United States
United States, Florida
University of Miami, Miller School of Medicine
Miami, Florida, United States
United States, Georgia
Medical College of Georgia
Augusta, Georgia, United States
United States, Illinois
RUSH University Medical Center
Chicago, Illinois, United States
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States
United States, Minnesota
the Mayo Clinic
Rochester, Minnesota, United States
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States
United States, North Carolina
Blumenthal Cancer Center
Charlotte, North Carolina, United States
United States, South Carolina
University of South Carolina
Charleston, South Carolina, United States
South Carolina Oncology Associates
Columbia, South Carolina, United States
Sponsors and Collaborators
Syndax Pharmaceuticals
Investigators
Study Chair: Alex Adjei, MD Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Jeannette Hasapidis, Executive Director of Clinical Operations, Syndax Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00750698     History of Changes
Other Study ID Numbers: SNDX-275-0403
Study First Received: September 8, 2008
Last Updated: March 17, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Syndax Pharmaceuticals:
lung cancer
non small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Entinostat
Erlotinib
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014