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

NCT01752023 | Terminated Phase 2 Results DMC

• 2 other identifiers: J1230NA_00067809
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

Response rates. Changes in tumor blood flow.

Conditions

Non-small Cell Lung Cancer Metastatic

Outcome Measures

Primary Outcomes (2)

• Objective Response Rates

  Per response evaluation criteria in solid tumors criteria

  6 weeks

• Tumor Blood Flow.

  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.

  6 weeks.

Secondary Outcomes (4)

• Median Time to Progression

  2 years.

• Adverse Effects

  2 years.

• Itraconazole Exposure Parameters

  2 years.

• Tumor Necrosis

  2 years.

Study Arms (2)

Cisplatin + Gemcitabine with SUBATM-itraconazole

EXPERIMENTAL

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: Cisplatin + Gemcitabine with SUBATM-itraconazole

Cisplatin + Gemcitabine

ACTIVE COMPARATOR

Arm B = Cisplatin 75 mg/m2 day 1, Gemcitabine 1000 mg/m2 days 1 + 8 for 6 cycles. Then Best supportive care.

Drug: Cisplatin + Gemcitabine

Interventions

Cisplatin + Gemcitabine with SUBATM-itraconazole DRUG

Experimental Arm

Also known as: SUBATM-itraconazole + Cisplatin and Gemcitabine for 6 cycles followed by SUBATM-itraconazole alone.

Cisplatin + Gemcitabine with SUBATM-itraconazole

Cisplatin + Gemcitabine DRUG

Active Comparator

Also known as: Cisplatin and Gemcitabine for 6 cyles followed by Best supportive care.

Cisplatin + Gemcitabine

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (2)

Bayview Medical Center at Johns Hopkins

Baltimore, Maryland, 21224, United States

Location

Johns Hopkins University, SKCCC

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Interventions

Cisplatin; Gemcitabine

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Ronan Kelly, MD
• Organization: SKCCC at Johns Hopkins

rkelly25@jhmi.edu

443-287-0005

Study Officials

• David Ettinger, MD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2012
• First Posted: December 18, 2012
• Study Start: March 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: October 17, 2018
• Results First Posted: June 2, 2017

Record last verified: 2018-09

Locations

US (2)