A Phase 1 Protocol of 5-Azacytidine and Erlotinib in Advanced Solid Tumor Malignancies

PRIMARY OBJECTIVES:

I. To document the toxicities, and reversibility of toxicities, of this regimen of 5-azacytidine (azacitidine) and erlotinib (erlotinib hydrochloride).

SECONDARY OBJECTIVES:

I. To determine any potential anti-tumor effects, as determined by the objective tumor response (complete and partial responses), clinical benefit (complete and partial responses, and clinical benefit), the time to tumor response, the time to tumor progression, and the overall survival.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor Malignancies
• Intervention / Treatment: Drug: 5-azacytidine, erlotinib; Drug: Erlotinib PO and Vidaza IV

Detailed Description

OUTLINE: This is a dose-escalation study.

Patients receive azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1 and 15, days 1-2 and 15-16, days 1-3 and 15-17, or days 1-4 and 15-18. Patients also receive erlotinib hydrochloride orally (PO) daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 28 days and then every 3 months for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must fulfill all of the following criteria to be eligible for study entry:
• Those who will be eligible will be all patients with non-hematologic neoplasms (lymphomas, leukemias, myeloma, myelodysplasia, or myeloproliferative syndromes) who have disease which has been previously treated and/or for which there is no acceptable standard treatment regimen available, and cannot be treated definitively with either surgery or radiotherapy. All will be appropriate candidates for treatment, and are not candidates for treatment with protocols of higher priority. All patients should have an ECOG/Zubrod/SWOG performance status of <2 at the time of the initiation of therapy, adequate end-organ function, no severe comorbid disease, and ability to provide informed consent.

Other Eligibility Criteria:

• Signed Informed Consent
• ECOG/Zubrod/SWOG Performance Status <2 (Karnofsky Performance Status > 70%)
• Life expectancy > 8 weeks
• Male or female' age >18 years
• Patients of childbearing potential must be using an effective means of contraception.
• Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine treatment.
• Histologic diagnosis of a solid tumor malignancy that is advanced and cannot be treated adequately by radiotherapy or surgery; or metastatic disease

• Baseline laboratory values (bone marrow, renal, hepatic):

  • Adequate bone marrow function:
  • Absolute neutrophil count >1000/µL
  • Platelet count >100'000/µL
  • Renal function:

• Serum creatinine < 1.5 x ULN

  • Hepatic function:

• Bilirubin <1.5x normal

  • Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels <=2 x ULN
  • Serum calcium < 12 mg/dl

Exclusion Criteria:

Patients meeting any of the following criteria are ineligible for study entry:

• Pregnant or lactating females
• Myocardial infarction or ischemia within the 6 months before Cycle 0' Day 0
• Uncontrolled' clinically significant dysrhythmia
• Prior radiotherapy to an indicator lesion unless there is objective evidence of tumor growth in that lesion
• Uncontrolled metastatic disease of the central nervous system
• Sensitivity to erlotinib, 5-azacytidine or mannitol
• Advanced hepatic tumors
• Radiotherapy within the 2 weeks before Cycle 1' Day 1
• Surgery within the 2 weeks before Cycle 1' Day 1
• Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 5; Erlotinib 150mg/day PO Day 1-28 and Vidaza 100mg/m2/day SQ Day 1-4 and 15-18	Drug: 5-azacytidine, erlotinib; Erlotinib 150 mg PO daily, days 1-8, and 15-22 5-Azacytidine 75 mg/m2/day, IV days 1 and 15; Other Names: Erlotinib :- Tarceva™ (OSI-774); Vidaza (5-azacytidine); Drug: Erlotinib PO and Vidaza IV; Patients enrolled to 1 of 5 cohorts, with varying drug doses and dose scheduling.
Experimental: Cohort 4; Erlotinib 200 mg/day PO Day 1-28 and Vidaza 75 mg/m2/day SQ 1-4 and 15-18	Drug: 5-azacytidine, erlotinib; Erlotinib 150 mg PO daily, days 1-8, and 15-22 5-Azacytidine 75 mg/m2/day, IV days 1 and 15; Other Names: Erlotinib :- Tarceva™ (OSI-774); Vidaza (5-azacytidine); Drug: Erlotinib PO and Vidaza IV; Patients enrolled to 1 of 5 cohorts, with varying drug doses and dose scheduling.
Experimental: Cohort 3; Erlotinib 150 mg/day PO Day 1-28 and Vidaza 75 mg/m2/day IV Day 1-3 and 15-17	Drug: 5-azacytidine, erlotinib; Erlotinib 150 mg PO daily, days 1-8, and 15-22 5-Azacytidine 75 mg/m2/day, IV days 1 and 15; Other Names: Erlotinib :- Tarceva™ (OSI-774); Vidaza (5-azacytidine); Drug: Erlotinib PO and Vidaza IV; Patients enrolled to 1 of 5 cohorts, with varying drug doses and dose scheduling.
Experimental: Cohort 2; Erlotinib 150 mg/day PO Day 1-28 and Vidaza 75 mg/m2/day IV Day 1-2 and 15-16	Drug: 5-azacytidine, erlotinib; Erlotinib 150 mg PO daily, days 1-8, and 15-22 5-Azacytidine 75 mg/m2/day, IV days 1 and 15; Other Names: Erlotinib :- Tarceva™ (OSI-774); Vidaza (5-azacytidine); Drug: Erlotinib PO and Vidaza IV; Patients enrolled to 1 of 5 cohorts, with varying drug doses and dose scheduling.
Experimental: Cohort 1; Erlotinib 150 mg/day PO Day 1-28 and Vidaza 75 mg/m2/day IV Day 1 and 15	Drug: 5-azacytidine, erlotinib; Erlotinib 150 mg PO daily, days 1-8, and 15-22 5-Azacytidine 75 mg/m2/day, IV days 1 and 15; Other Names: Erlotinib :- Tarceva™ (OSI-774); Vidaza (5-azacytidine); Drug: Erlotinib PO and Vidaza IV; Patients enrolled to 1 of 5 cohorts, with varying drug doses and dose scheduling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Quality and quantity of adverse events due to administration of erlotinib + 5-azacytidine, as therapy for the treatment of advanced or metastatic cancer.	4 years

Collaborators and Investigators

• Sponsor: New Mexico Cancer Care Alliance
• Investigators: Principal Investigator: Julie E Bauman, M.D., University of New Mexico Cancer Center

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: October 14, 2009
• First Submitted That Met QC Criteria: October 15, 2009
• First Posted (Estimate): October 16, 2009

Study Record Updates

• Last Update Posted (Estimate): May 1, 2013
• Last Update Submitted That Met QC Criteria: April 30, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Erlotinib; Tarceva; Vidaza; 5-azacytidine; Advanced Solid Tumor Malignancies
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride; Azacitidine
• Other Study ID Numbers: INST 0710C; NCI-2011-02646 (Registry Identifier: NCI CTRP)