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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier:
NCT00996515
First received: October 14, 2009
Last updated: April 30, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Advanced Solid Tumor Malignancies
Drug: 5-azacytidine, erlotinib
Drug: Erlotinib PO and Vidaza IV
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Protocol of 5-Azacytidine and Erlotinib in Advanced Solid Tumor Malignancies

Resource links provided by NLM:


Further study details as provided by New Mexico Cancer Care Alliance:

Primary Outcome Measures:
  • Quality and quantity of adverse events due to administration of erlotinib + 5-azacytidine, as therapy for the treatment of advanced or metastatic cancer. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: June 2008
Study Completion Date: September 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00996515

Locations
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
Sponsors and Collaborators
New Mexico Cancer Care Alliance
Investigators
Principal Investigator: Julie E Bauman, M.D. University of New Mexico Cancer Center
  More Information

No publications provided

Responsible Party: New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier: NCT00996515     History of Changes
Other Study ID Numbers: INST 0710C, NCI-2011-02646
Study First Received: October 14, 2009
Last Updated: April 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by New Mexico Cancer Care Alliance:
Advanced Solid Tumor Malignancies
Erlotinib
Vidaza
Tarceva
5-azacytidine

Additional relevant MeSH terms:
Neoplasms
Azacitidine
Erlotinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014