Protocol Number: 09-C-0018

Title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Oral Talactoferrin in Addition to Best Supportive Care in Adults with Non-Small Cell Lung Cancer (NSCLC) Who Have Failed Two or More Prior Treatment Regimens

Number:

09-C-0018

Summary:

Background:

• (Bullet) Patients with stage IIIB/IV NSCLC have a very poor prognosis despite chemotherapy, and radiation treatments. After second line therapy their median survival is between 6-8 months.

• (Bullet) Talactoferrin alfa (TLF) is a recombinant human lactoferrin, that displays anti-infective and anti-inflammatory properties, anti-tumor activity and anti-asthma properties.

• (Bullet) Previous studies in NSCLC demonstrated evidence of clinical activity. In A randomized, double blind, placebo controlled, Phase II study of oral recombinant human lactoferrin (rhLF) monotherapy in patients with stage IIIB/IV NSCLC who have failed 1st or 2nd line chemotherapy showed a 2.3 months increase in median Overall Survival (p less than 0.05, one-tailed). Talactoferrin appeared to be well tolerated in this study.

Objectives:

• (Bullet) Primary: Compare overall survival between Talactoferrin arm and placebo arm

• (Bullet) Secondary Objectives: Compare six month and one year survival rate, progression-free survival, objective tumor response rate, disease stabilization rate and safety and tolerability between Talactoferrin arm and placebo arm

• (Bullet) Tertiary Objective: Compare Quality of Life in English-speaking patients between Talactoferrin arm and placebo arm

Inclusion Criteria:

• (Bullet) Age greater than or equal to 18 years, histologically or cytologically confirmed stage IIIB/IV NSCLC confirmed at the NCI Lab of Pathology prior to starting treatment

• (Bullet) Received at least 2 prior systemic anti-cancer therapies for stage IIIB/IV NSCLC, one of which was a platinum-containing regimen.

• (Bullet) At least one target lesion that is unirradiated and measurable by RECIST

• (Bullet) Adequate organ function and Karnofsky PS of greater than 50 (ECOG 0, 1, or 2)

Exclusion Criteria:

• (Bullet) History of allergic reactions to compounds of similar chemical or biologic composition to talactoferrin or any GI tract disease resulting in the inability to take oral medications

Design:

• (Bullet) This is a double blind, placebo-controlled, multicenter, Phase III study. Approximately 720 patients will be randomized at a ratio of 2:1 to the talactoferrin or placebo arm, respectively.

• (Bullet) The two study arms are as follows:

• (Bullet) Arm 1: Talactoferrin 1.5 g bid orally

• (Bullet) Arm 2: Placebo bid orally

Each talactoferrin or placebo cycle will include 12 weeks (84 days) on study drug and 2 weeks (14 days) off study drug. Patients will receive talactoferrin or placebo for up to a maximum of five 14-week cycles (70 weeks), until the occurrence of progressive disease, start of a next-line therapy for NSCLC, unacceptable toxicity, withdrawal of consent, or withdrawal by investigator, whichever occurs first.

• (Bullet) Evaluation will be performed at baseline, at week 7 and week 14 and then every cycle (14 weeks) with CT Chest/Abdomen.

• (Bullet) This study is designed to have approximately 85% power to detect a 30% improvement in median Overall Survival (OS) in patients in the intent to treat population, from 4.6 months in the placebo arm to 6.0 months in the talactoferrin arm with a two-sided p-value of 0.05.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

1. Age greater than or equal to 18 years.

2. Histologically or cytologically confirmed stage IIIB or IV NSCLC

3. Failed at least 2 prior systemic anti-cancer regimens for advanced or metastatic NSCLC. The following criteria must be satisfied:

- Failure is defined as disease progression or unacceptable

toxicity

- The patient must have received a platinum-containing

regimen

- Failure to the most recent systemic anti-cancer regimen must

have occurred

4. At least one target lesion that is unirradiated and measurable by RECIST

5. Hemoglobin greater than or equal to 9.0 g/dL

6. Absolute neutrophil count greater than or equal to 2000/mm(3)

7. Lymphocytes greater than or equal to 800/ mm(3)

8. Platelet count greater than or equal to 100,000/ mm(3)

9. Total bilirubin less than or equal to 1.5 mg/dL

10. Creatinine less than or equal to 2.0 mg/dL

11. AST (SGOT) and ALT (SGPT) less than or equal to 2.5 x the upper limit of normal (ULN)

12. Lactate dehydrogenase less than or equal to 1.5 x ULN

13. Karnofsky performance status of greater than 50 (ECOG 0, 1, or 2)

14. Life expectancy of greater than 12 weeks

15. Able to understand and sign an informed consent

EXCLUSION CRITERIA:

1. Presence of brain metastases, unless the patient received brain irradiation, including adequate stereotactic radiosurgery, at least 4 weeks prior to randomization, and is stable, asymptomatic, and off steroids for at least 3 weeks prior to randomization

2. History of allergic reactions to compounds of similar chemical or biologic composition to talactoferrin

3. Any gastrointestinal tract disease or other medical condition resulting in the inability to take oral medications

4. History of other malignancies except: (i) adequately treated basal or squamous cell carcinoma of the skin; (ii) curatively treated, a) in situ carcinoma of the uterine cervix, b) prostate cancer, or c) superficial bladder cancer; or (iii) other curatively treated solid tumor with no evidence of disease for greater than or equal to 5 years

5. Uncontrolled ischemic heart disease, or uncontrolled symptomatic congestive heart failure

6. Serious active infection

7. Psychiatric illness / social situations that would limit study compliance

8. Other uncontrolled serious chronic disease or conditions that in the investigator's opinion could affect compliance or follow-up in the protocol

9. Concurrent radiotherapy to any site or radiotherapy within 4 weeks prior to randomization or previous radiotherapy to the target lesion sites (the sites that are to be followed for determination of a response)

10. Known HIV positive or on active anti-retroviral therapy

11. Known Hepatitis B surface antigen positive or hepatitis C positive

12. Receipt of any investigational medication within 4 weeks prior to randomization

13. Pregnant or lactating patients, or fertile female patients with a positive pregnancy test (serum beta-human chorionic gonadotropin [beta- hCG] at screening or at baseline), or fertile female patients unwilling to use adequate contraception during treatment and 30 days after completion of treatment

14. Sexually active male patients unwilling to practice contraception while participating on the study and up to 30 days after completion of treatment

15. Legal incapacity or limited legal capacity, unless authorization is granted by a legal guardian

Special Instructions:

Currently Not Provided

Keywords:

NSCLC

QOL

Recombinant Human Lactoferrin

Recruitment Keyword(s):

Non-Small Cell Lung Cancer

NSCLC

Condition(s):

NSCLC

Investigational Drug(s):

Talactoferrin

Investigational Device(s):

None

Intervention(s):

Drug: Talactoferrin

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O'Rourke M, Levitan N,Gressot L, Vincent M, Burkes R, Coughlin S, Kim Y, Berille J. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000 May;18(10):2095-103.

Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR, Dunphy F, Kalman L, Miller V, Lee JS, Moore M, Gandara D, Karp D, Vokes E, Kris M, Kim Y, Gamza F, Hammershaimb L. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol. 2000 Jun;18(12):2354-62.

Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1;22(9):1589-97.

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