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

This study has been terminated.
(Interim analysis showed that the primary endpoint would not be met.)
Sponsor:
Information provided by (Responsible Party):
CytRx
ClinicalTrials.gov Identifier:
NCT01337154
First received: April 15, 2011
Last updated: June 27, 2013
Last verified: June 2013
  Purpose

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 Intervention 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 Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by CytRx:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Within 18 months of study start. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 18 months of study start. ] [ Designated as safety issue: No ]
    Objective tumor response will be evaluated using the RECIST 1.1 criteria.

  • Overall survival [ Time Frame: Within 24 months of study start. ] [ Designated as safety issue: No ]
  • Assessment of quality of life [ Time Frame: Within 24 months of study start. ] [ Designated as safety issue: No ]
    EORTC QLQ-C30 version 3.


Enrollment: 140
Study Start Date: April 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01337154

Locations
United States, California
Desert Hematology Oncology Medical Group, Inc.
Rancho Mirage, California, United States, 92270
United States, Kansas
Kansas City Cancer Center
Kansas City, Kansas, United States, 66112
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Bulgaria
Department of Medical Oncology, Specialized Hospital for Active Treatment of Oncological Diseases
Sofia, Bulgaria, 1233
Medical Oncology Clinic, Multiprofile Hospital for Active Treatment
Varna, Bulgaria, 9010
Department of Medical Oncology, Complex Oncology Center
Veliko Tarnovo, Bulgaria, 5000
India
NIZAM's Institute of Medical Sciences
Hyderabad, Andhra Pradesh, India, 500082
M S Patel Cancer Centre, Shree Krishna Hospital
Anand, Gujarat, India, 388 325
Curie Manavata Cancer Centre
Nashik, Maharashtra, India, 411013
Shatabdi Super Speciality Hospital
Nashik, Maharashtra, India, 422 005
Noble Hospital
Pune, Maharashtra, India, 411013
Dr. Kamakshi Memorial Hospital
Chennai, Pallikaranai, India, 600100
G Kuppuswamy Naidu Memorial Hospital, Valvadi Narayanaswamy Cancer Centre
Coimbatore, Pappanaickenpalayam, India, 641037
Orchid Nursing Home
Kolkata, West Bengal, India, 700054
Mexico
Instituto Nacional de Cancerologia
Mexico City, Mexico
Russian Federation
State Medical Institution: Arkhangelsk Regional Clinical Oncology Center
Arkhangelsk, Russian Federation, 163045
State Therapeutical and Prophylatic Institution: Chelyabinsk Regional Clinical Oncology Center
Chelyabinsk, Russian Federation, 454087
State Medical Instituion Kursk Regional Oncology Center
Kursk, Russian Federation, 305035
Non-State Medical Institution: Central Clinical Hospital #2
Moscow, Russian Federation, 129128
St. Petersburg State Healthcare Institution: City Clinical Oncology Center
Saint-Pertersburg, Russian Federation, 197022
Ukraine
Public Institution: Dnipropetrovsk City Multispeciality Clinical Hospital #4
Dnipropetrovsk, Ukraine, 49102
Public Clinical Treatment and Prophylaxis Instituion: Donetsk Regional Antitumor Center
Donetsk, Ukraine, 83092
Ivano-Frankivsk Regional Oncology Center
Ivano-Frankivsk, Ukraine, 76018
Public Healthcare Instituion: Kharkiv Regional Clinical Oncology Center
Kharkiv, Ukraine, 61070
Kyiv City Clinical Oncology Center
Kyiv, Ukraine, 03115
Zakarpattia Regional Clinical Oncology Center
Uzhhorod, Ukraine, 88014
Sponsors and Collaborators
CytRx
Investigators
Principal Investigator: Oscar Arrieta, M.D. Instituto Nacional de Cancerologia, Columbia
  More Information

No publications provided

Responsible Party: CytRx
ClinicalTrials.gov Identifier: NCT01337154     History of Changes
Other Study ID Numbers: TAMI-P2-NSCLC-01
Study First Received: April 15, 2011
Last Updated: June 27, 2013
Health Authority: United States: Food and Drug Administration
Mexico: Ministry of Health

Keywords provided by CytRx:
NSCLC
non-small cell lung cancer
tamibarotene

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Pleural Effusion
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pleural Diseases
Benzoates
Carboplatin
Paclitaxel
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 20, 2014