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

New Mexico Cancer Care Alliance

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumor Malignancies

Treatments: Drug: Erlotinib PO and Vidaza IV; Drug: 5-azacytidine, erlotinib

Study type: Interventional

Funder types: Other

Identifiers

NCT00996515

INST 0710C

NCI-2011-02646 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 5 patient groups

Cohort 5

Experimental group

Description:

Erlotinib 150mg/day PO Day 1-28 and Vidaza 100mg/m2/day SQ Day 1-4 and 15-18

Treatment:

Drug: 5-azacytidine, erlotinib

Drug: Erlotinib PO and Vidaza IV

Cohort 4

Experimental group

Description:

Erlotinib 200 mg/day PO Day 1-28 and Vidaza 75 mg/m2/day SQ 1-4 and 15-18

Treatment:

Drug: 5-azacytidine, erlotinib

Drug: Erlotinib PO and Vidaza IV

Cohort 3

Experimental group

Description:

Erlotinib 150 mg/day PO Day 1-28 and Vidaza 75 mg/m2/day IV Day 1-3 and 15-17

Treatment:

Drug: 5-azacytidine, erlotinib

Drug: Erlotinib PO and Vidaza IV

Cohort 2

Experimental group

Description:

Erlotinib 150 mg/day PO Day 1-28 and Vidaza 75 mg/m2/day IV Day 1-2 and 15-16

Treatment:

Drug: 5-azacytidine, erlotinib

Drug: Erlotinib PO and Vidaza IV

Cohort 1

Experimental group

Description:

Erlotinib 150 mg/day PO Day 1-28 and Vidaza 75 mg/m2/day IV Day 1 and 15

Treatment:

Drug: 5-azacytidine, erlotinib

Drug: Erlotinib PO and Vidaza IV