Erlotinib and AT-101 in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients With Epidermal Growth Factor Receptor (EGFR) Activating Mutations

This study has been terminated.
Sponsor:
Collaborator:
Ascenta Therapeutics
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00988169
First received: September 30, 2009
Last updated: November 22, 2011
Last verified: November 2011
  Purpose

Advanced stage lung cancer is generally treated with anti-cancer medication called chemotherapy. Most lung cancer is caused by cigarette smoking. However, some lung cancers develop in people who never smoked or who only smoked for a short period of time. This type of lung cancer may respond to a medication called erlotinib (Tarceva). Erlotinib is an anticancer pill that is approved by the Food and Drug Administration (FDA) for use in patients with advanced lung cancer. Unfortunately, erlotinib does not work for all patients or only works for a period of time. The doctors are trying to find ways to improve the effect of erlotinib by combining it with another anti-cancer medication.

Ascenta Therapeutics, Inc. has developed a drug called AT-101 as a potential treatment for cancer. AT-101 is an investigational drug. That means that AT-101 is not approved by the United States Food and Drug Administration (FDA) for general use. The FDA does permit its use in studies like this one to determine whether it is safe and effective.

This is the first study to examine the effects of AT-101 and erlotinib. It is hoped that by combining AT-101 with erlotinib, AT-101 may help erlotinib work better to shrink lung cancer. Studies that have been performed in the laboratory suggest that AT-101 in combination with erlotinib may be more effective at shrinking tumors than erlotinib alone.


Condition Intervention Phase
Lung Cancer
Drug: oral erlotinib and pulsed doses of oral AT-101
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Erlotinib and AT-101 in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients With EGFR Activating Mutations

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Radiographic objective response rate (CR+PR, by WHO criteria for standard bidimensional tumor measurement) after one 21-day cycle of combination therapy with erlotinib and AT-101 [ Time Frame: 21 days after cycle one ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Safety and toxicity of the combination of erlotinib and AT-101 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Comparison of volumetric tumor measurement with standard bidimensional measurement, to assess utility as endpoint for future studies [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Correlative studies including: Bcl-2 expression and related family members and regulators by immunohistochemistry [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: September 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: oral erlotinib and pulsed doses of oral AT-101
This will be an open-label, single institution, phase II trial. The study will assess the efficacy of the combination of the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, and the novel pan-Bcl-2 inhibitor, AT-101, in treatment-naïve advanced (Wet Stage IIIB and IV)NSCLC patients with EGFR activating mutations A planned pause of 21 days will be performed after enrollment of the 10th and 20th patient to assess for excessive toxicity.
Drug: oral erlotinib and pulsed doses of oral AT-101
Patients will receive oral erlotinib 100 mg daily and pulsed doses of oral AT-101 given 40 mg twice daily on days 1-3 of a 21-day cycle. If the initial combination of erlotinib and AT-101 is tolerated, dose escalation of erlotinib to 150 mg daily will be allowed at the discretion of the treating investigator at the start of cycle 2. Patients will continue receiving treatment on study until they refuse further therapy, develop evidence of progressive disease, or develop unacceptable toxicity or a medical condition that would, in the judgment of the investigator,

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability to understand and the willingness to sign a written informed consent form; the consent form must be signed by the patient prior to any study-specific procedures.
  • Patients age ≥ 18 years with histologically confirmed wet Stage IIIB (with malignant pleural effusion) or Stage IV non-small cell lung cancer (metastatic or recurrent).
  • Pathologic confirmation of non-small cell lung cancer at Memorial Sloan-Kettering Cancer Center.
  • Presence of exon 19 or exon 21 EGFR activating mutation.
  • No prior EGFR tyrosine kinase therapy.
  • No prior systemic therapy for advanced NSCLC (Stage IIIB with malignant effusion or Stage IV)
  • Karnofsky performance status > or = to 70% OR ECOG performance status ≤ 2.
  • Measurable disease defined as greater than or equal to one known/suspected malignant lesion > or = to 1 cm measurable in two dimensions.
  • Adequate hematologic, renal, and/or hepatic function: WBC > or = to 3,000/ul, hemoglobin > or = to 9.0 g/dl, platelet count > or = to 100,000/ul, total bilirubin ≤ 1.5 X UNL, AST ≤ 2.5 X UNL, and serum creatinine within 1.5 x the upper limit of normal (<1.95 at MSKCC) or calculated creatinine clearance > or = to 60 ml/min.
  • Able to swallow and retain oral medication.
  • Willingness and ability to comply with study procedures and follow-up examination.
  • Four weeks since any major surgery, completion of radiation, or completion of all prior chemotherapy.
  • Acute toxicities of any prior therapy must have resolved to < Grade 1 or baseline prior to starting study therapy.
  • Effective contraception.

Exclusion Criteria:

  • Prior treatment with gefitinib, erlotinib, or other EGFR tyrosine kinase inhibitor therapy.
  • Concurrent cytotoxic or biological therapy.
  • Known KRAS mutation.
  • History within the past 6 months of myocardial infarction, cardiac stent placement, or intermittent ischemia with troponin leak.
  • Active secondary malignancy or history of other malignancy within the last 3 years except non-melanoma skin cancer and in-situ carcinoma of the cervix.
  • Active, serious comorbid medical conditions including severe infection, malnutrition, unstable angina, congestive heart failure (New York Heart Association Class III or IV), pulmonary fibrosis, or condition that would be felt by treating physician to preclude safe participation in the clinical trial.
  • Patients with malabsorption syndrome or diseases significantly affecting the gastrointestinal tract including prior gastric resection or small bowel resection, inflammatory bowel disease, or partial or complete small bowel obstruction.
  • Unstable brain or leptomeningeal metastases including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
  • Women who are pregnant or breast-feeding.
  • Inability/unwillingness to comply with protocol treatment or follow-up.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00988169

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Ascenta Therapeutics
Investigators
Principal Investigator: Naiyer Rizvi, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00988169     History of Changes
Other Study ID Numbers: 09-026
Study First Received: September 30, 2009
Last Updated: November 22, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
AT-101
erlotinib
Unresectable Stage IIIB
09-026

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Erlotinib
Gossypol
Gossypol acetic acid
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Contraceptive Agents, Male
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Contraceptive Agents, Female
Spermatocidal Agents
Antispermatogenic Agents

ClinicalTrials.gov processed this record on September 18, 2014