An Open-Label Pharmacodynamic Study of Bevacivumab and Pazopanib in Renal Cell Carcinoma

NCT00992121 | Completed Phase 1

• 1 other identifier: 111687
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine whether blood tests, tumour imaging and tumour tissue analysis can reveal effects of drugs that block blood vessel growth (angiogenesis) in patients with renal cancer.

Conditions

Carcinoma, Renal Cell

Keywords

pazopanib; Renal Cell Carcinoma; Kidney; cancer; bevacizumab

Outcome Measures

Primary Outcomes (1)

• Tumour size, as measured by the sum of the longest diameters of all target lesions on CT

  6 weeks

Secondary Outcomes (1)

• Plasma levels of pharmacodynamic markers of study drug effect

  6 weeks Part I; 15 weeks Part II; 6 weeks during maintenance therapy

Study Arms (2)

Part I and 2 week dosing Part II

OTHER

Part I - bevacizumab 3 infusions at 2 week intervals Part II - pazopanib dosing 2 weeks in 3-week cycles

Drug: Bevacizumab; Drug: Pazopanib 2 week

Part I and 3 week dosing Part II

OTHER

Part I - bevacizumab 3 infusions at 2 week interval, Part II - pazopanib dosing 3 weeks in 3-week cycles

Drug: Bevacizumab; Drug: Pazopanib 3 week

Interventions

Bevacizumab DRUG

Bevacizumab - 3 infusions of 10mg/kg administered at 2 week intervals - Part I

Part I and 2 week dosing Part II; Part I and 3 week dosing Part II

Pazopanib 2 week DRUG

Pazopanib for first 2 weeks of each 3-week cycles as follows: 1) 200 mg twice weekly, 2) 200 mg every other day, 3) 200 mg qd, 4) 400 mg qd, 5) 800 mg qd, and 6) 1200 mg qd (Group 1). Maintenance pazopanib 800 mg qd for all 3 weeks throughout repeating 3-week cycles. Number of cycles: until death, loss of clinical benefit, unacceptable toxicity, or withdrawal from the study for other reasons.

Part I and 2 week dosing Part II

Pazopanib 3 week DRUG

Pazopanib throughout each 3-week cycle as follows: 1) 200 mg twice weekly, 2) 200 mg every other day, 3) 200 mg qd, 4) 400 mg qd, 5) 800 mg qd, and 6) 1200 mg qd (Group 1). Maintenance pazopanib 800 mg qd for all 3 weeks throughout repeating 3-week cycles. Number of cycles: until death, loss of clinical benefit, unacceptable toxicity, or withdrawal from the study for other reasons.

Part I and 3 week dosing Part II

Eligibility Criteria

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

You may qualify if:

• Histologically (any histological subtype) or cytologically confirmed unresectable RCC with a clear cell component.
• Experienced documented evidence of radiological progression based on Response Evaluation Criteria in Solid Tumors \[RECIST\] while on first line (or greater) RCC therapy and within 6 months prior to the first dose of study medication (bevacizumab).
• Evidence of unidimensionally measurable disease (i.e., at least 1 malignant tumour mass that can be accurately measured in at least 1 dimension with the longest diameter greater than or equal to 20 mm with conventional CT or MRI or V10 mm with spiral CT scan \[if spiral CT scan is used, minimum lesion size should be twice the reconstruction interval used, e.g., if reconstruction size is 7 mm, lesion size should be greater than or equal to 14 mm\]) Note: Subject should be excluded if all baseline measurable lesions are within previously irradiated areas.
• Free of any malignant disease other than RCC for at least 5 years prior to the first dose of study medication (bevacizumab) in this study, with the exception of the following: Cervical carcinoma in situ, Melanoma in situ, Basal or squamous cell carcinoma of the skin
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
• Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, or surgical procedures to NCI CTCAE Grade 1 or less.
• Adequate organ function as defined by laboratory ranges Note: Laboratory values just outside of these ranges may be included if in the view of the investigator and medical monitor, these findings will not interfere with the study or pose an unacceptable risk to the subject.
• Capable of giving written informed consent, and willing and able to comply with the requirements and restrictions listed in the consent form.
• Males and females greater than or equal to 18 years of age at screening. A female subject is eligible to participate if she is of non-childbearing potential (see below) or if she is of childbearing potential and agrees to use one of the defined contraception methods from the time of first dose of study medication (bevacizumab) until 4 months after the last dose of study medication (bevacizumab or pazopanib).
• Non-childbearing potential is defined as pre-menopausal females with a documented bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or postmenopausal females with 12 months of spontaneous amenorrhea. If the exact duration of amenorrhea is unknown, a blood sample with simultaneous follicle stimulating hormone (FSH) greater than or equal to 40 MIU/mL and estradiol less than or equal to 40 pg/mL (less than or equal to 140 pmol/L) will be required as confirmation. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the approved contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
• A male subject is eligible to participate if he agrees to use one of the contraception methods listed in from the time of first dose of study medication (bevacizumab) until 4 months after the last dose of study medication (bevacizumab or pazopanib).

You may not qualify if:

• In the opinion of the Investigator, the subject would derive continued therapeutic benefit from anti-angiogenic therapy.
• In the opinion of the Investigator, there are no safety concerns that would present an unacceptable benefit:risk profile for treatment with pazopanib.
• The subject is able to swallow and retain oral medication.
• Clinical evidence of cancer metastatic to the central nervous system or leptomeningeal carcinomatosis.
• Previous treatment with bevacizumab or pazopanib, either alone or in combination with other therapy.
• Note: Patients who have previously received treatment with cytokine or anti-angiogenic agents other than bevacizumab and pazopanib may be considered for the study.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to bevacizumab or pazopanib or components of bevacizumab or pazopanib (other than active drugs), or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates participation.
• Any other anticancer therapy (radiotherapy, chemotherapy, or immunotherapy) within 28 days prior to the first dose of study medication and extending through completion of treatment and all study procedures. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
• Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study medication.
• Assessable disease is unsuitable for biopsy or the patient is unwilling or not sufficiently fit to undergo serial biopsies of their cancer at the time points specified in Section 4.7.
• A major surgical procedure or traumatic injury within 28 days prior to the first dose of study medication (bevacizumab), or anticipation of a major surgical procedure (that cannot be rescheduled) from the first dose of study mediciation through 28 days after the last dose of study medication. The investigator should confirm that any prior surgical incision has fully healed prior to initiating treatment.
• Evidence of active bleeding or bleeding diathesis, or any serious, non-healing wound, ulcer, or bone fracture.
• Hemoptysis within 6 weeks of the first dose of study medication.
• Use of therapeutic doses of warfarin within 5 half-lives of the first dose of study medication and during treatment in the study. Note: Use of low molecular weight heparin is permitted during the study. Patients may be switched from warfarin to low molecular weight heparin for the duration of this study if, in the opinion of the Investigator, doing so does not present an undue safety risk to the patient.
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 hemorrhage within 28 days of the first dose of study medication.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Related Links

• Results for study 111687 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasms

Interventions

Bevacizumab; pazopanib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2009
• First Posted: October 9, 2009
• Study Start: November 18, 2009
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: November 13, 2017

Record last verified: 2017-11

Locations

GB (1)