Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III, Phase II	Treatment	Active	18 to 70	Other	IFCT-0703 Eudract : 2008-004897-41, NCT00775307

Trial Description

Summary

The aim of this study is to evaluate the efficacy and safety of pazopanib compared with placebo in patients with T < or = 5 cm, N0 (stage I according to TNM 2009) completely resected NSCLC.

Further Study Information

The study will be conducted in two phases as follows:

• The Phase II component of the study will be a randomized, double-blind, placebo-controlled, multi-centre study performed in France only. After undergoing NSCLC resection, 112 patients will be randomized to receive either pazopanib 800 mg per day or placebo for 24 weeks.

• The Phase III component of the study will be a randomized, double-blind, placebo-controlled, multi-centre study performed internationally. Patients who have completed the Phase II component of the study will be followed and included in the Phase III. Additional patients will also be recruited to a planned total of 355 patients per treatment arm. New patients will be randomized to receive either pazopanib 800 mg per day or placebo for 24 weeks.

Eligibility Criteria

Inclusion Criteria:

1. Complete resection of the primary tumour and local extension has to be performed. All margins must be free of microscopical disease. At the time of resection, a complete mediastinal lymph-node resection or lymph-node sampling is required. Surgeons are encouraged to dissect or sample all accessible nodal levels.

2. Single surgically resected pathological stage I NSCLC lesion: consisting of a tumor < 5 cm in greatest dimension (see TNM staging on Appendix 10).

3. No regional lymph node involvement.

4. Pre-operative petscan

5. Satisfactory healing of surgical wound.

6. Patients >= 18 and < 70 years of age.

7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

8. Recruited to the study and available to start treatment investigational product at least 4 weeks but no longer that 8 weeks after the surgical resection of the NSCLC.

9. No approved or investigational anti-cancer therapy concurrently or in the 5 years prior to start of study drug, including tumor embolization, chemotherapy, radiation therapy, immunotherapy, hormone therapy, biologic therapy, or anti angiogenic therapy (e.g., inhibitors of VEGF or VEGFR).

10. Adequate organ system function

11. Ability to swallow and retain oral medication.

12. A female is eligible to enter and participate in this study if she is of:

Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has undergone:

• Hysterectomy.

• Bilateral oophorectomy (ovariectomy).

• Bilateral tubal ligation.

• Or who is post-menopausal:

• Patients not using hormone replacement therapy (HRT) must have experienced total cessation of menses for ≥1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone value >40 mIU/mL and an estradiol value <40 pg/mL (<140 pmol/L).

• Patients must discontinue HRT prior to study enrolment due to the potential for inhibition of cytochrome enzymes that metabolize estrogens and progestins. For most forms of HRT, at least 2 4 weeks must elapse between the cessation of HRT and determination of menopausal status; length of this interval depends on the type and dosage of HRT. If a female subject is determined not to be post-menopausal, they must use adequate contraception, as defined immediately below. Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception. Contraceptive methods acceptable to the IFCT, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:

• An intrauterine device with a documented failure rate of less than 1% per year.

• Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.

• Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product.

• Double-barrier contraception (condom with spermicidal jelly, foam suppository or film; diaphragm with spermicide; or male condom and diaphragm with spermicide). Note: Oral contraceptives are not reliable due to potential drug drug interactions.

Female patients who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 15 days following the last dose of study drug. A male with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception or abstinence during the study.

13. French Patients: in France, a patient will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security insurance.

Exclusion Criteria:

1. Prior malignancy. Note: Patients who have had another malignancy and were treated more than 5 years ago and have since been considered cured, or patients with a history of basocellular skin carcinoma or in situ carcinoma of the uterine cervix are eligible.

2. Presence of any concurrent disease or condition that would make the subject inappropriate for study participation including any unresolved or unstable, serious toxicity from prior administration of another investigational drug or any serious medical disorder that would interfere with the subject's safety, obtaining informed consent, or compliance with all study related procedures.

3. Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to beginning therapy, or anticipation of the need for a major surgical procedure during the course of the study.

4. History or clinical evidence of nodal or distant metastases (screening of brain metastasis is mandatory).

5. Bronchioalveolar carcinoma of lobar or multi lobar involvement. Bronchioalveolar carcinomas presenting as a discrete solitary radiological mass or nodule are eligible.

6. History of human immunodeficiency virus infection or chronic hepatitis B or C.

7. History of hemoptysis after resection of lung cancer.

8. Clinically significant gastrointestinal abnormalities including, but not limited to:

• Malabsorption syndrome

• Disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect the absorption of study drug.

• Active peptic ulcer disease

• Inflammatory bowel disease

• Ulcerative colitis, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis or other gastrointestinal condition increasing the risk of perforation.

• History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment

9. Presence of active or uncontrolled infection.

10. Evidence of active bleeding or bleeding diathesis.

11. History of any one or more of the following cardiovascular conditions within the past 6 months:

• Coronary/peripheral artery bypass graft, cardiac angioplasty or stenting.

• Myocardial infarction.

• Severe/unstable angina pectoris.

• Symptomatic peripheral vascular disease pulmonary embolism, thromboembolic event, cerebrovascular accident or transient ischemic attack.

• Class III or IV congestive heart failure, as defined by the New York Heart Association.

12. Poorly controlled hypertension (defined as a systolic blood pressure (SBP) of >= 140 mmHg or diastolic blood pressure (DBP) >= 90 mmHg.

Note: Initiation or adjustment of anti-hypertensive medication(s) is permitted prior to study entry. Blood pressure (BP) must be re-assessed on two occasions separated by at least 5 minutes. The mean SBP/DBP values from both BP assessments must be <140/90 mmHg in order for a subject to be eligible for the study.

13. Following abnomalies on ECG : Q wave, ischemia, QT > 450 msec, atrio-ventricular block 2 or 3, atrial fibrilation

14. Therapeutic anticoagulation treatment.

15. Chronic daily treatment with aspirin (≥ 325 mg/day) or non-steroidal anti-inflammatory agents known to inhibit platelet function. Treatment with dipyridamole, ticlopidine, clopidogrel and/or cilostazol is also not allowed.

16. Pregnant or lactating female.

17. Concurrent treatment with an investigational agent or participation in another clinical trial.

18. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib.

Trial Contact Information

Trial Lead Organizations/Sponsors

French Thoracic Oncology Intergroup Center

Benjamin BESSE, Dr

Principal Investigator

Jean-Charles SORIA, Pr

Study Director

Franck Morin
		Email: franck.morin@ifct.fr

Elodie Amour
		Email: elodie.amour@ifct.fr

France
	CAEN
	Centre Regional Francois Baclesse
		Radj Gervais, Pr
		Radj Gervais, Dr	Principal Investigator
	CHU de Caen
		Gerard Zalcman, Pr
	Clamart
	Hopital d'Instruction des Armees Percy
		Fabien VAYLET, Dr
	Grenoble
	CHU de Grenoble - Hopital de la Tronche
		Denis Moro-Sibilot, Pr
		Denis Moro-Sibilot, Pr	Principal Investigator
	Marseille
	Hopital Sainte Marguerite
		Fabrice BARLESI, Dr
	PARIS
	Hopital Tenon
		Bernard MILLERON, Dr
	Pierre Bénite
	Centre Hospitalier Lyon Sud
		Pierre-Jean Souquet, Dr
	Strasbourg
		Elisabeth Quoix, Pr	Principal Investigator
	Hopital Lyautey
		Elisabeth Quoix, Pr
	Toulouse
	CHU de Toulouse, Hotel Dieu
		Julien Mazieres, Pr
	VILLEJUIF
	Institut Gustave Roussy
		Benjamin BESSE, Dr	Ph: +33 1 42 11 42 11

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00775307
Information obtained from ClinicalTrials.gov on May 13, 2009