First Line Study of Tamibarotene in Combination for Advanced Non-Small Cell Lung Cancer

Sponsor

CytRx (Industry)

Overall Status

Terminated

CT.gov ID

NCT01337154

Collaborator

(none)

140

Enrollment

Locations

Arms

Duration (Months)

5.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Stage IIIB Non-small Cell Lung Cancer With Pleural Effusion Stage IV Non-small Cell Lung Cancer	Drug: Tamibarotene Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

140 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2011

Actual Primary Completion Date :

Jun 1, 2013

Actual Study Completion Date :

Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tamibarotene Subjects will receive tamibarotene, 6 mg/m2, divided as twice daily orally starting 1 week before chemotherapy and continuing through all 6 cycles and through the duration of the study. Chemotherapy will include paclitaxel (IV; 200 mg/m2) and carboplatin (IV; AUC=6)administered once every 3 weeks for up to 6 cycles.	Drug: Tamibarotene Tablet, 6 mg/m2, oral, divided into twice a day dosing.
Placebo Comparator: Placebo Subjects will take an equal number of placebo tablets as the group receiving tamibarotene divided as twice daily orally, starting 1 week before chemotherapy and continuing through all 6 cycles and through the duration of the study. Paclitaxel (IV; 200 mg/m2) and carboplatin (IV; AUC=6) will be administered once every 3 weeks for up to 6 cycles.	Drug: Placebo Tablets, orally, daily

Arm

Intervention/Treatment

Experimental: Tamibarotene

Subjects will receive tamibarotene, 6 mg/m2, divided as twice daily orally starting 1 week before chemotherapy and continuing through all 6 cycles and through the duration of the study. Chemotherapy will include paclitaxel (IV; 200 mg/m2) and carboplatin (IV; AUC=6)administered once every 3 weeks for up to 6 cycles.

Drug: Tamibarotene

Tablet, 6 mg/m2, oral, divided into twice a day dosing.

Placebo Comparator: Placebo

Subjects will take an equal number of placebo tablets as the group receiving tamibarotene divided as twice daily orally, starting 1 week before chemotherapy and continuing through all 6 cycles and through the duration of the study. Paclitaxel (IV; 200 mg/m2) and carboplatin (IV; AUC=6) will be administered once every 3 weeks for up to 6 cycles.

Drug: Placebo

Tablets, orally, daily

Outcome Measures

Primary Outcome Measures

Progression-free survival [Within 18 months of study start.]
Progression-free survival (PFS) is defined as the time from enrollment (i.e., assignment of subject ID number) to first documentation of objective tumor progression or to death due to any cause in the absence of previous documentation of objective tumor progression.

Secondary Outcome Measures

Objective response rate [Within 18 months of study start.]
Objective tumor response will be evaluated using the RECIST 1.1 criteria.
Overall survival [Within 24 months of study start.]
Assessment of quality of life [Within 24 months of study start.]
EORTC QLQ-C30 version 3.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Desert Hematology Oncology Medical Group, Inc.	Rancho Mirage	California	United States	92270
2	Kansas City Cancer Center	Kansas City	Kansas	United States	66112
3	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
4	Department of Medical Oncology, Specialized Hospital for Active Treatment of Oncological Diseases	Sofia		Bulgaria	1233
5	Medical Oncology Clinic, Multiprofile Hospital for Active Treatment	Varna		Bulgaria	9010
6	Department of Medical Oncology, Complex Oncology Center	Veliko Tarnovo		Bulgaria	5000
7	NIZAM's Institute of Medical Sciences	Hyderabad	Andhra Pradesh	India	500082
8	M S Patel Cancer Centre, Shree Krishna Hospital	Anand	Gujarat	India	388 325
9	Curie Manavata Cancer Centre	Nashik	Maharashtra	India	411013
10	Shatabdi Super Speciality Hospital	Nashik	Maharashtra	India	422 005
11	Noble Hospital	Pune	Maharashtra	India	411013
12	Dr. Kamakshi Memorial Hospital	Chennai	Pallikaranai	India	600100
13	G Kuppuswamy Naidu Memorial Hospital, Valvadi Narayanaswamy Cancer Centre	Coimbatore	Pappanaickenpalayam	India	641037
14	Orchid Nursing Home	Kolkata	West Bengal	India	700054
15	Instituto Nacional de Cancerologia	Mexico City		Mexico
16	State Medical Institution: Arkhangelsk Regional Clinical Oncology Center	Arkhangelsk		Russian Federation	163045
17	State Therapeutical and Prophylatic Institution: Chelyabinsk Regional Clinical Oncology Center	Chelyabinsk		Russian Federation	454087
18	State Medical Instituion Kursk Regional Oncology Center	Kursk		Russian Federation	305035
19	Non-State Medical Institution: Central Clinical Hospital #2	Moscow		Russian Federation	129128
20	St. Petersburg State Healthcare Institution: City Clinical Oncology Center	Saint-Pertersburg		Russian Federation	197022
21	Public Institution: Dnipropetrovsk City Multispeciality Clinical Hospital #4	Dnipropetrovsk		Ukraine	49102
22	Public Clinical Treatment and Prophylaxis Instituion: Donetsk Regional Antitumor Center	Donetsk		Ukraine	83092
23	Ivano-Frankivsk Regional Oncology Center	Ivano-Frankivsk		Ukraine	76018
24	Public Healthcare Instituion: Kharkiv Regional Clinical Oncology Center	Kharkiv		Ukraine	61070
25	Kyiv City Clinical Oncology Center	Kyiv		Ukraine	03115
26	Zakarpattia Regional Clinical Oncology Center	Uzhhorod		Ukraine	88014