Adjuvant Pazopanib in Stage I NSCLC

NCT ID: NCT00775307

Last Updated: 2019-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 142 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2016-04-18

Brief 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.

Detailed Description

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, 140 patients will be randomized to receive either pazopanib 400 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 400 mg per day or placebo for 24 weeks.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

B

Placebo 400 mg/day (24 weeks)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo 400 mg/day (24 weeks)

A

Pazopanib 400 mg/day (24 weeks)

Group Type: EXPERIMENTAL

PAZOPANIB

Intervention Type: DRUG

400 mg/day (24 weeks)

Interventions

PAZOPANIB

400 mg/day (24 weeks)

Intervention Type: DRUG

Placebo

Placebo 400 mg/day (24 weeks)

Intervention Type: DRUG

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. 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).
• Subject using HRT must have experienced total cessation of menses for ≥ 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT.

Childbearing potential, including any female who has had a negative serum pregnancy test within 1 week 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.
• Male partner sterilization (vasectomy with documentation of azoospermia) 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 and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)
• Oral contraceptive, either combined or progestogen alone [Hatcher, 2004]
• Injectable progestogen [Hatcher, 2004]
• Implant of levonorgestrel [Hatcher, 2004]
• Estrogenic vaginal ring [Hatcher, 2004]
• Percutaneous contraceptive patches [Hatcher, 2004]

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 anomalies 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 or untreated deep venous thrombosis (DVT), cerebrovascular accident or transient ischemic attack.

Note : Subject with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible

• Class III or IV congestive heart failure, as defined by the New York Heart Association (Appendix 5).

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 anomalies on ECG : Q wave, ischemia, QT > 480 msec, atrio-ventricular block 2 or 3, atrial fibrillation

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Intergroupe Francophone de Cancerologie Thoracique

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benjamin BESSE, Dr

Role: PRINCIPAL_INVESTIGATOR

Institut Gustave Roussy (IGR)

Jean-Charles SORIA, Pr

Role: STUDY_DIRECTOR

Institut Gustave Roussy (IGR)

Locations

CHU

Nîmes, , France

Orléans - CH

Orléans, , France

Paris - Saint Louis

Paris, , France

Paris - hôpital Saint-Antoine

Paris, , France

Paris - Hopital Tenon

Paris, , France

Pau - CH

Pau, , France

Centre Catalan d'Onologie

Perpignan, , France

Lyon Sud

Pierre-Bénite, , France

Reims - CHU

Reims, , France

Rennes - CHU

Rennes, , France

Strasbourg - NHC

Strasbourg, , France

Thonon les bains - CH

Thonon-les-Bains, , France

Toulon - HIA

Toulon, , France

Toulouse - CHU Larrey

Toulouse, , France

Nancy - CHU

Vandœuvre-lès-Nancy, , France

Vesoul - CHI

Vesoul, , France

Villejuif - Institut Gustave Roussy

Villejuif, , France

Annemasse - CH

Ambilly, , France

Béziers - CH

Béziers, , France

Bobigny - Hôpital Avicenne

Bobigny, , France

Bordeaux - Polyclinique Nord

Bordeaux, , France

Boulogne - Ambroise Paré

Boulogne, , France

Caen - Centre François Baclesse

Caen, , France

Caen - CHU Côte de Nacre

Caen, , France

Clamart - Hôpital Percy

Clamart, , France

Clermont Ferrand - CHU

Clermont-Ferrand, , France

Colmar - CH

Colmar, , France

Dax - CH

Dax, , France

Grenoble - CHU

Grenoble, , France

Le Mans - Centre Hospitalier

Le Mans, , France

Lille - Hôpital Calmette

Lille, , France

Mantes La Jolie - CH

Mantes-la-Jolie, , France

Marseille - Hôpital Sainte Marguerite

Marseille, , France

Metz - Clinique Claude Bernard

Metz, , France

Mont de Marsan - CH

Mont-de-Marsan, , France

Montpellier - Clinique Clémentville

Montpellier, , France

Montpellier - CHRU

Montpellier, , France

Moulins - CH

Moulins, , France

Nantes - Centre René Gauducheau

Nantes, , France

Nevers - CH

Nevers, , France

Countries

France

References

Besse B, Mazieres J, Ribassin-Majed L, Barlesi F, Bennouna J, Gervais R, Moreau L, Berard H, Debieuvre D, Molinier O, Moro-Sibilot D, Souquet PJ, Jacquot S, Petit L, Lena H, Pignon JP, Lacas B, Morin F, Milleron B, Zalcman G, Soria JC; Intergroupe Francophone de Cancerologie Thoracique (IFCT). Pazopanib or placebo in completely resected stage I NSCLC patients: results of the phase II IFCT-0703 trial. Ann Oncol. 2017 May 1;28(5):1078-1083. doi: 10.1093/annonc/mdx070.

Reference Type: RESULT

PMID: 28327934 (View on PubMed)

Related Links

http://www.ifct.fr

IFCT official website

Other Identifiers

Eudract : 2008-004897-41

Identifier Type: -

Identifier Source: secondary_id

IFCT-0703

Identifier Type: -

Identifier Source: org_study_id