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

Phase 2

Terminated

• Conditions: Non Small Cell Lung Cancer
• Interventions: Drug: Entinostat; Drug: Erlotinib

• Registration Number: NCT00750698
• Lead Sponsor: Syndax Pharmaceuticals

Brief Summary

To evaluate the tumor responses to SNDX-275 (entinostat) in combination with continued erlotinib in participants with non-small Cell Lung Carcinoma (NSCLC) who are progressing on erlotinib.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-08
• Study First Submitted: 2008-09-08
• Study First Submitted QC: 2008-09-08
• Study First Posted: 2008-09-10
• Primary Completion: 2010-05
• Study Completion: 2010-06
• Results First Submitted: 2023-06-12
• Status Verified: 2023-07
• Results First Submitted QC: 2023-07-05
• Last Update Submitted: 2023-07-05
• Results First Posted: 2023-07-06
• Last Update Posted: 2023-07-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

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 participant's screening into the study)
3. Recovered from any toxicity associated with the most recent cancer treatment (no greater than grade 1 toxicity on Common Terminology Criteria for Adverse Events scale or to prior baseline condition)
4. At least 1 measurable lesion ≥ 20 millimeters (mm) by conventional computed tomography (CT) scan or ≥ 10 mm by spiral CT scan
5. Eastern Cooperative Oncology Group 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 grams/deciliter; platelets ≥ 75 x 10^9/liter (L); absolute neutrophil count ≥ 1.0 x 10^9/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. Aspartate aminotransferase and alanine aminotransferase 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 entinostat
14. Participant or legally acceptable representative has granted written informed consent before any study-specific procedure (including special screening tests) is performed

Exclusion Criteria

1. Prior stem cell transplant
2. Symptomatic central nervous system involvement
3. Prior treatment with an histone deacetylase 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 intravenous antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis B or C infection
12. Abnormal cardiac function as defined as clinically significant findings on electrocardiogram (multifocal premature ventricular complexes, 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 multigated acquisition 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. Participant is currently enrolled in (or completed within 28 days) another investigational drug study
18. Participant unavailable for on-study or follow-up assessments
19. Participant has any kind of medical, psychiatric, or behavioral disorder that places the participant at increased risk for study participation or compromises the ability of the participant to give written informed consent and/or to comply with study procedures and requirements

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Erlotinib-responsive	Entinostat	Participants self-administered entinostat in combination with continued erlotinib self-administration. "Erlotinib-responsive" participants are those who progressed following either a complete or partial response to erlotinib or a period of stable disease lasting at least 3 months.
Erlotinib-responsive	Erlotinib	Participants self-administered entinostat in combination with continued erlotinib self-administration. "Erlotinib-responsive" participants are those who progressed following either a complete or partial response to erlotinib or a period of stable disease lasting at least 3 months.
Erlotinib-nonresponsive	Entinostat	Participants self-administered entinostat in combination with continued erlotinib self-administration. "Erlotinib-nonresponsive" participants are those who either progressed immediately during treatment with erlotinib (after at least 1 full cycle of erlotinib treatment) or had an objective response or period of stable disease lasting less than 3 months.
Erlotinib-nonresponsive	Erlotinib	Participants self-administered entinostat in combination with continued erlotinib self-administration. "Erlotinib-nonresponsive" participants are those who either progressed immediately during treatment with erlotinib (after at least 1 full cycle of erlotinib treatment) or had an objective response or period of stable disease lasting less than 3 months.

Primary Outcome Measures

Name	Time	Method
Disease Control Rate (Complete Response, Partial Response, or Stable Disease for at Least 3 Months	At least 3 months

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival Rate	Up to 4 months

Trial Locations

Locations (5)

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Sharp Clinical Oncology Research; 🇺🇸 San Diego, California, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States