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

• Sponsor: Syndax Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00750698
• Collaborator: (none)
• Enrollment: 8
• Locations: 12
• Arms: 2
• Duration (Months): 22
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: SNDX-275; Drug: erlotinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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 Names: entinostat ; Drug: erlotinib; erlotinib (150 mg PO QD) for up to six (6) 28-day cycles; Other Names: 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 Names: entinostat ; Drug: erlotinib; erlotinib (150 mg PO QD) for up to six (6) 28-day cycles; Other Names: Tarceva

Outcome Measures

Primary Outcome Measures

1. Disease control rate (complete response, partial response, or stable disease for at least 3 months) [3 months]

Secondary Outcome Measures

1. Progression-free survival rate at 2 months [2 months]

2. Progression-free survival rate at 4 months [4 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States
2	University of California San Diego	La Jolla	California	United States
3	Sharp Memorial Hospital	San Diego	California	United States
4	University of Miami, Miller School of Medicine	Miami	Florida	United States
5	Medical College of Georgia	Augusta	Georgia	United States
6	RUSH University Medical Center	Chicago	Illinois	United States
7	University of Maryland Medical Center	Baltimore	Maryland	United States
8	the Mayo Clinic	Rochester	Minnesota	United States
9	Roswell Park Cancer Institute	Buffalo	New York	United States
10	Blumenthal Cancer Center	Charlotte	North Carolina	United States
11	University of South Carolina	Charleston	South Carolina	United States
12	South Carolina Oncology Associates	Columbia	South Carolina	United States

Sponsors and Collaborators

• Syndax Pharmaceuticals

Investigators

• Study Chair: Alex Adjei, MD, Roswell Park Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Syndax Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00750698
• Other Study ID Numbers: SNDX-275-0403
• First Posted: Sep 10, 2008
• Last Update Posted: May 2, 2022
• Last Verified: Apr 1, 2022

• Keywords provided by Syndax Pharmaceuticals: lung cancer; non small cell lung cancer
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride; Entinostat

Study Results

No Results Posted as of May 2, 2022