Clinical trial NCT01337154: First Line Study of Tamibarotene in Combination for Advanced Non-Small Cell Lung Cancer
Official title: A Randomized, Placebo-Controlled Phase 2b Study of Tamibarotene Plus Paclitaxel and Carboplatin Versus Placebo Plus Paclitaxel and Carboplatin as First Line Treatment for Subjects With Advanced Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Stage IIIB Non-small Cell Lung Cancer With Pleural Effusion
Stage IV Non-small Cell Lung Cancer
Keywords: NSCLC
non-small cell lung cancer
tamibarotene
Lead sponsor: CytRx
Sponsor class: INDUSTRY
First posted: 2011-04-18
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this study is to determine the progression-free survival and objective response rate in subjects with either stage IIIB with pleural effusion NSCLC or stage IV NSCLC who are treated with up to six cycles of paclitaxel plus carboplatin and either tamibarotene or placebo. Subjects will be randomly assigned to receive tamibarotene, 6 mg/m2, divided as twice daily orally, or an equal number of matching placebo tablets, starting 1 week before chemotherapy and continuing through all 6 cycles and beyond. Subjects will be assessed for response on Day 50, Day 113, then every other month using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).


Eligibility criteria: Inclusion Criteria:

* Subjects must be at least 18 years of age
* Subjects must have pathological findings consistent with primary non-small cell lung cancer of any histology.
* Subjects must have either stage IIIB with pleural effusion or IV NSCLC with radiographically measurable disease (RECIST 1.1 criteria). Women non-smokers with stage IV NSCLC should be screened for EGFR mutation and if positive be excluded from the study and placed on an EGFR kinase inhibitor.
* Subjects must have an ECOG Performance Status ≤2.
* If corticosteroids are required for controlling cerebral edema, subjects must be on a stable dose for at least 1 week.
* Subjects must have recovered from any toxicity of prior therapies.
* Subjects must be at least 4 weeks removed from surgery or radiation therapy.
* Subjects must have a life expectancy of at least 12 weeks.
* Subjects must have adequate bone marrow function (defined as an absolute neutrophil count of ≥1500 cells/mm3 and platelet count ≥100,000 cells/mm3), liver function with total bilirubin ≤2.0 mg/dL, and serum creatinine ≤1.5 x institutional ULN.
* Subjects must be able to understand and be willing to sign a written informed consent document.
* Tamibarotene, as with all retinoids, is teratogenic. Therefore, female subjects of childbearing potential must agree to use 2 effective methods of contraception (hormonal, barrier method of birth control, or abstinence) and sexually-active male subjects must agree to use an effective method of contraception (hormonal or barrier method of birth control or abstinence) while participating in this study and for six months afterwards. Women of childbearing potential must have a negative pregnancy test ≤1 week prior to registration.
* Subjects must be able to swallow tablets.
* If available, tumor specimens must be submitted for immunohistochemistry analyses with their pathology reports.

Exclusion Criteria:

* Subjects who have received or are currently receiving chemotherapy or antibody therapy, or are enrolled in another treatment clinical trial.
* Subjects with a coagulopathy or bleeding disorder.
* Clinically evident congestive heart failure \>class II of the New York Heart Association (NYHA) guidelines.
* Serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
* History or signs of active coronary artery disease with or without angina pectoris (i.e. myocardial infarction with 6 months prior to enrollment, uncontrolled angina, electrocardiographic evidence of acute ischemia).
* Subjects who have a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol or may not be able to comply with the safety monitoring requirements of the study.
* HIV-positive subjects; however, subjects will not be routinely screened for HIV.
* Subjects who are allergic to any of the intended chemotherapies.
* Female subjects who are pregnant or breast-feeding.
* Active, clinically significant serious infection requiring treatment with antibiotics, antivirals, or antifungals.
* Subjects with peripheral neuropathy ≥grade 2
* Prior systemic treatment for locally advanced or metastatic disease (exception below): Prior adjuvant chemotherapy for Stage I-III or combined modality chemotherapy-radiation for locally advanced disease allowed if completed \>12 months prior to randomization.
* Subjects with brain metastases are only eligible if treated and neurologically stable with no ongoing requirement for corticosteroids, e.g., dexamethasone, for at least 2 weeks.
* Subjects with hypertriglyceridemia (\>1000 mg/dL).
* Subjects with elevated liver function tests if AST is ≥2.5x the institutional or central laboratory's upper limit of normal for subjects without liver metastases, or \>5x the institutional or central laboratory's upper limit of normal for subjects with liver metastases.
* Subjects with HbA1c ≥8.0.
* Subjects taking vitamin A either as a supplement or as part of a multivitamin unless there has been at least a 2 week washout.
* Subjects using concomitant medications that are known inducers or inhibitors of CYP3A4 up to 14 days before Cycle 1 Day 1 (pimozide, diltiazem, erythromycin, clarithromycin, and quinidine, and amiodarone) should be excluded from the study.
* Subjects whose tumors cannot be adequately measured per RECIST 1.1.

Primary outcomes:
measure: Progression-free survival
timeFrame: Within 18 months of study start.
Secondary outcomes:
measure: Objective response rate
timeFrame: Within 18 months of study start.
measure: Overall survival
timeFrame: Within 24 months of study start.
measure: Assessment of quality of life
timeFrame: Within 24 months of study start.
Other outcomes:
Locations:
city: Rancho Mirage
country: United States
facility: Desert Hematology Oncology Medical Group, Inc.
state: California
city: Kansas City
country: United States
facility: Kansas City Cancer Center
state: Kansas
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Sofia
country: Bulgaria
facility: Department of Medical Oncology, Specialized Hospital for Active Treatment of Oncological Diseases
city: Varna
country: Bulgaria
facility: Medical Oncology Clinic, Multiprofile Hospital for Active Treatment
city: Veliko Tarnovo
country: Bulgaria
facility: Department of Medical Oncology, Complex Oncology Center
city: Hyderabad
country: India
facility: NIZAM's Institute of Medical Sciences
state: Andhra Pradesh
city: Anand
country: India
facility: M S Patel Cancer Centre, Shree Krishna Hospital
state: Gujarat
city: Nashik
country: India
facility: Curie Manavata Cancer Centre
state: Maharashtra
city: Nashik
country: India
facility: Shatabdi Super Speciality Hospital
state: Maharashtra
city: Pune
country: India
facility: Noble Hospital
state: Maharashtra
city: Chennai
country: India
facility: Dr. Kamakshi Memorial Hospital
state: Pallikaranai
city: Coimbatore
country: India
facility: G Kuppuswamy Naidu Memorial Hospital, Valvadi Narayanaswamy Cancer Centre
state: Pappanaickenpalayam
city: Kolkata
country: India
facility: Orchid Nursing Home
state: West Bengal
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cancerologia
city: Arkhangelsk
country: Russian Federation
facility: State Medical Institution: Arkhangelsk Regional Clinical Oncology Center
city: Chelyabinsk
country: Russian Federation
facility: State Therapeutical and Prophylatic Institution: Chelyabinsk Regional Clinical Oncology Center
city: Kursk
country: Russian Federation
facility: State Medical Instituion Kursk Regional Oncology Center
city: Moscow
country: Russian Federation
facility: Non-State Medical Institution: Central Clinical Hospital #2
city: Saint-Pertersburg
country: Russian Federation
facility: St. Petersburg State Healthcare Institution: City Clinical Oncology Center
city: Dnipropetrovsk
country: Ukraine
facility: Public Institution: Dnipropetrovsk City Multispeciality Clinical Hospital #4
city: Donetsk
country: Ukraine
facility: Public Clinical Treatment and Prophylaxis Instituion: Donetsk Regional Antitumor Center
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Oncology Center
city: Kharkiv
country: Ukraine
facility: Public Healthcare Instituion: Kharkiv Regional Clinical Oncology Center
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Oncology Center
city: Uzhhorod
country: Ukraine
facility: Zakarpattia Regional Clinical Oncology Center
Study officials:
affiliation: Instituto Nacional de Cancerologia, Columbia
name: Oscar Arrieta, M.D.
role: PRINCIPAL_INVESTIGATOR
References: