A Randomized Phase II Study of SUBATM-itraconazole in Patients With Untreated Squamous NSCLC. (NA_00067809)

This study has been terminated.
(Low Accrual)
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01752023
First received: December 14, 2012
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

Response rates.

Changes in tumor blood flow.


Condition Intervention Phase
Non-small Cell Lung Cancer Metastatic
Drug: Arm A
Drug: Arm B
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of SUBATM-itraconazole With Cisplatin/Gemcitabine in Patients With Previously Untreated Metastatic Squamous Non-Small Cell Lung Cancer.

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Objective response rates [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    To determine the objective response rates of cisplatin and gemcitabine with or without SUBATM-itraconazole in patients with chemotherapy-naïve metastatic squamous non-small cell lung cancer.

  • Tumor blood flow. [ Time Frame: 6 weeks. ] [ Designated as safety issue: No ]
    To assess the changes in tumor blood flow as measured by contrast enhanced MRI scanning in patients with metastatic squamous non-small cell lung cancer treated with cisplatin and gemcitabine with or without SUBATM-itraconazole.


Secondary Outcome Measures:
  • Median time to progression [ Time Frame: 2 years. ] [ Designated as safety issue: No ]
    To determine the median time to progression and median duration of survival of patients with metastatic squamous non-small cell lung cancer treated with cisplatin and gemcitabine with or without SUBATM-itraconazole.

  • Adverse effects [ Time Frame: 2 years. ] [ Designated as safety issue: Yes ]
    To characterize the adverse effects of cisplatin and gemcitabine with or without SUBATM-itraconazole in this patient population.

  • Itraconazole exposure parameters [ Time Frame: 2 years. ] [ Designated as safety issue: No ]
    To correlate itraconazole exposure parameters with median time to progression and median survival in this patient population.

  • Tumor necrosis [ Time Frame: 2 years. ] [ Designated as safety issue: No ]
    To assess changes in tumor necrosis in response to cisplatin and gemcitabine with or without SUBATM-itraconazole.


Enrollment: 3
Study Start Date: December 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
SUBATM-itraconazole 200 mg BID, Cisplatin 75 mg/m2 day 1, Gemcitabine 1000 mg/m2 days 1 + 8 for 6 cycles. Then SUBATM-itraconazole 200 mg BID alone.
Drug: Arm A
Experimental Arm
Other Name: SUBATM-itraconazole + Cisplatin and Gemcitabine for 6 cycles followed by SUBATM-itraconazole alone.
Active Comparator: Arm B
Arm B = Cisplatin 75 mg/m2 day 1, Gemcitabine 1000 mg/m2 days 1 + 8 for 6 cycles. Then Best supportive care.
Drug: Arm B
Active Comparator
Other Name: Cisplatin and Gemcitabine for 6 cyles followed by Best supportive care.

Detailed Description:

To determine the objective response rates of cisplatin and gemcitabine with or without SUBATM-itraconazole in patients with chemotherapy-naïve metastatic squamous non-small cell lung cancer.

To assess the changes in tumor blood flow as measured by contrast enhanced MRI scanning in patients with metastatic squamous non-small cell lung cancer treated with cisplatin and gemcitabine with or without SUBATM-itraconazole.

  Eligibility

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

Inclusion Criteria:

Stage IV squamous cell lung cancer, with no prior systemic chemotherapy.

Patients who have received prior adjuvant chemotherapy for early-stage lung cancer are eligible if at least 6 months have elapsed from completion of that treatment.

Patients whose tumors contain mixed non-small cell histologies are eligible if squamous carcinoma is the predominant histology. Mixed tumors with small cell anaplastic elements are not eligible.

Patient must have measurable disease per RECIST 1.1 (defined in section 9.1.2).

Patients with previous radiotherapy as definitive therapy for locally advanced non-small cell lung cancer are eligible, as long as the recurrence is outside the original radiation therapy port. Radiation therapy must have been completed greater than or equal to 2 weeks prior to enroll in this study.

Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of itraconazole or SUBATM-itraconazole in combination with gemcitabine/cisplatin in patients under 18 years of age, such patients are excluded from this study. Squamous cell lung cancer is exceedingly rare in children.

Life expectancy of at least 12 weeks.

Eastern Cooperative Oncology Group performance status 0 - 1.

Patients must have adequate organ and marrow function.

Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Prior treatment with gemcitabine, cisplatin (except in the adjuvant setting), itraconazole or SUBATM-itraconazole.

Uncontrolled brain metastases. Patients with brain metastases must have stable neurologic status following local therapy (surgery or radiation) for at least 2 weeks, and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to itraconazole, SUBATM-itraconazole, gemcitabine, cisplatin or other agents used in the study.

Itraconazole is a strong CYP3A4 inhibitor and may increase plasma concentrations of drugs metabolized by this pathway. Co-administration of cisapride, midazolam, pimozide, quinidine, lovastatin, simvastatin, triazolam, dofetilide, or levacetylmethadol (levomethadyl) with SUBATM-itraconazole or itraconazole is contraindicated.

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Pregnant women are excluded from this study because itraconazole is Class C agent and both gemcitabine and cisplatin are Class D agents, with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SUBATM-itraconazole and gemcitabine/cisplatin, breastfeeding should be discontinued if the mother is to be treated on this protocol.

HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with SUBATM-itraconazole, gemcitabine, or cisplatin with these essential mediations.

Medical contra-indication to MRI (e.g. gadolinium allergy, or severe claustrophobia).

  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: NCT01752023

Locations
United States, Maryland
Johns Hopkins University, SKCCC
Baltimore, Maryland, United States, 21287
Bayview Medical Center at Johns Hopkins
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01752023     History of Changes
Other Study ID Numbers: J1230, NA_00067809
Study First Received: December 14, 2012
Last Updated: June 25, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Cisplatin
Itraconazole
Hydroxyitraconazole
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
14-alpha Demethylase Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014