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

NCT01337154 | Terminated Phase 2 DMC

• 1 other identifier: TAMI-P2-NSCLC-01
• Study Type: interventional
• Target: 140
• Locations: 6 countries
• Sites: 26

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).

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

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  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.

  Within 18 months of study start.

Secondary Outcomes (3)

• Objective response rate

  Within 18 months of study start.

• Overall survival

  Within 24 months of study start.

• Assessment of quality of life

  Within 24 months of study start.

Study Arms (2)

Tamibarotene

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Tamibarotene DRUG

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

Tamibarotene

Placebo DRUG

Tablets, orally, daily

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CytRx: lead

Study Sites (26)

Desert Hematology Oncology Medical Group, Inc.

Rancho Mirage, California, 92270, United States

Location

Kansas City Cancer Center

Kansas City, Kansas, 66112, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Department of Medical Oncology, Specialized Hospital for Active Treatment of Oncological Diseases

Sofia, 1233, Bulgaria

Location

Medical Oncology Clinic, Multiprofile Hospital for Active Treatment

Varna, 9010, Bulgaria

Location

Department of Medical Oncology, Complex Oncology Center

Veliko Tarnovo, 5000, Bulgaria

Location

NIZAM's Institute of Medical Sciences

Hyderabad, Andhra Pradesh, 500082, India

Location

M S Patel Cancer Centre, Shree Krishna Hospital

Anand, Gujarat, 388 325, India

Location

Curie Manavata Cancer Centre

Nashik, Maharashtra, 411013, India

Location

Shatabdi Super Speciality Hospital

Nashik, Maharashtra, 422 005, India

Location

Noble Hospital

Pune, Maharashtra, 411013, India

Location

Dr. Kamakshi Memorial Hospital

Chennai, Pallikaranai, 600100, India

Location

G Kuppuswamy Naidu Memorial Hospital, Valvadi Narayanaswamy Cancer Centre

Coimbatore, Pappanaickenpalayam, 641037, India

Location

Orchid Nursing Home

Kolkata, West Bengal, 700054, India

Location

Instituto Nacional de Cancerologia

Mexico City, Mexico

Location

State Medical Institution: Arkhangelsk Regional Clinical Oncology Center

Arkhangelsk, 163045, Russia

Location

State Therapeutical and Prophylatic Institution: Chelyabinsk Regional Clinical Oncology Center

Chelyabinsk, 454087, Russia

Location

State Medical Instituion Kursk Regional Oncology Center

Kursk, 305035, Russia

Location

Non-State Medical Institution: Central Clinical Hospital #2

Moscow, 129128, Russia

Location

St. Petersburg State Healthcare Institution: City Clinical Oncology Center

Saint-Pertersburg, 197022, Russia

Location

Public Institution: Dnipropetrovsk City Multispeciality Clinical Hospital #4

Dnipropetrovsk, 49102, Ukraine

Location

Public Clinical Treatment and Prophylaxis Instituion: Donetsk Regional Antitumor Center

Donetsk, 83092, Ukraine

Location

Ivano-Frankivsk Regional Oncology Center

Ivano-Frankivsk, 76018, Ukraine

Location

Public Healthcare Instituion: Kharkiv Regional Clinical Oncology Center

Kharkiv, 61070, Ukraine

Location

Kyiv City Clinical Oncology Center

Kyiv, 03115, Ukraine

Location

Zakarpattia Regional Clinical Oncology Center

Uzhhorod, 88014, Ukraine

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

tamibarotene

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Oscar Arrieta, M.D.

  Instituto Nacional de Cancerologia, Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2011
• First Posted: April 18, 2011
• Study Start: April 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: June 28, 2013

Record last verified: 2013-06

Locations

ME (1); UA (6); BU (3); RU (5); IN (8); US (3)