Pazopanib Plus Lapatinib Compared to Lapatinib Alone and Pazopanib Alone In Subjects With Metastatic Cervical Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00430781
• Date of registration: 31/01/2007
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline
• Public title: Pazopanib Plus Lapatinib Compared to Lapatinib Alone and Pazopanib Alone In Subjects With Metastatic Cervical Cancer
• Scientific title: A Phase II, Open-Label, Randomized, Multicenter Trial of Pazopanib (GW786034) in Combination With Lapatinib (GW572016) Compared to Pazopanib Monotherapy and Lapatinib Monotherapy in Subjects With FIGO Stage IVB or Recurrent or Persistent Cervical Cancer With Zero or One Prior Chemotherapy Regimen
• Date of first enrolment: November 2006
• Target sample size: 228
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00430781
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

Argentina, Belgium, Canada, Estonia, France, Germany, India, Ireland, Italy, Mexico, Peru, Spain, Thailand, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- A subject will be eligible for inclusion in this study only if all of the following
criteria are met:

- Signed, written informed consent prior to performing any study-related procedures

- Female subjects =18 years of age

- FIGO Stage IVB, or recurrent or persistent cervical cancer

- Life expectancy of at least 12 weeks

- ECOG status of 0 or 1.

- Histologically confirmed FIGO Stage IVB, or recurrent or persistent squamous cell
carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not
amenable to curative treatment with surgery and/or radiation therapy

- Measurable disease, defined as at least one lesion that can be accurately measured in
at least one dimension (longest dimension to be recorded). Each lesion must be = 20 mm
when measured by conventional techniques, including palpitation, plain x-ray, CT and
MRI, or =10 mm when measured by spiral CT.

- At least one "target lesion" to be used to assess response as defined by Response
Evaluation Criteria in Solid Tumors (RECIST; Terasse, 2000). Tumors within a
previously irradiated field will be designated as "non-target" lesions unless
progression is documented or a biopsy is obtained to confirm persistence at least 90
days following completion of radiation therapy.

- Received 0 or 1 prior chemotherapy regimen for metastatic disease.

- Note: Chemotherapy given in combination with radiation therapy as a radiosensitizer
does not count toward this prior therapy limit

- Recovered from the effects of surgery or chemotherapy. At least three weeks must have
elapsed from the last administration of chemotherapy.

- Adequate organ and bone marrow function as defined in Table 1.

- Table 1:(Definitions for Adequate Organ Function)

- System:(Laboratory Values)

- Hematologic: Absolute neutrophil count (ANC)(= 1.5 X 109/L)Hemoglobin1(=9
g/dL)Platelets(=100 X 109/L)

- Hepatic: Total bilirubin (=1.5 X ULN)AST and ALT (=2.5 X ULN)

- Renal: Calculated creatinine clearance2 (=50 mL/min)

- Urine protein3 (Negative, trace or +1 by dipstick urinalysis or <1.0 gram determined
by 24 hour urine protein analysis.)

- Subjects may not have had a transfusion within 7 days of screening assessment.

- Calculated by Cockcroft Gault formula See Appendix 7: Renal Function Tests

- A patient should first be screened with dipstick urinalysis. If urine protein by
dipstick analysis is =2+, then a 24-hour urine protein must be assessed and 24 hour
urine protein must be <1 g protein to be eligible.

- Ability to swallow and retain oral medication.

- 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 had:

- A hysterectomy

- A bilateral oophorectomy (ovariectomy)

- A bilateral tubal ligation

- Is post-menopausal (total cessation of menses for = 1 year)

- Childbearing potential, has 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. GSK acceptable contraceptive methods, when
used consistently and in accordance with both the product label and the instructions
of the physician, are as follows:

- 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
investigation 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.

- Subjects must provide written informed consent prior to performance of study specific
procedures or assessments, and must be willing to comply with treatment and follow-up
as outlined in the protocol. Procedures conducted as apart of routine clinical
management of the patient (e.g., blood count, imaging study) and obtained prior to
signed informed consent may be utilized for screening purposes provided these tests
are obtained as specified in the protocol

Exclusion Criteria:

- A subject will not be eligible for inclusion in this study if any of the following
criteria apply:

- Neuroendocrine or small cell carcinoma of the cervix.

- Prior use of any biologic therapy with VEGF, VEGFR, or ErbB1/ErbB2 inhibitors.

- Concurrent cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy,
biologic therapy, hormonal therapy, and tumor embolization).

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

- Use of an investigational anti-cancer drug within 28 days or 5 half-lives, whichever
is longer, preceding the first dose of study medication.

- Has taken or is taking prohibited medications listed in the protocol.

- Any serious and/or unstable pre-existing medical, psychiatric, or other conditions
that could interfere with patient's safety, obtaining informed consent or compliance
to the study.

- History of another malignancy. Note: Patients who have had another malignancy and have
been disease-free for 5 years, or patients with a history of completely resected
non-melanomatous skin carcinoma or successfully treated in situ carcinoma are
eligible.

- History or clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis. Routine screening with CNS imaging studies (computed
tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically
indicated.

- Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel.

- Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal
condition increasing the risk of perforation; history of abdominal fistula,
gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to
beginning therapy.

- Presence of uncontrolled infec


Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

Metastatic Cervical Cancer

Neoplasms, Uterine Cervix

Intervention(s)

Drug: lapatinib (GW572016)

Drug: pazopanib (GW786034)

Primary Outcome(s)

Progression-free Survival (PFS) in Interim Analysis [Time Frame: From randomization until at least 35 PFS events in pairwise comparison of the three treatment arms (Interim Analysis; up to 52.14 weeks)]

Progression-free Survival (PFS) in Final Analysis [Time Frame: From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)]

Secondary Outcome(s)

Clinical Benefit Response [Time Frame: From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)]

Overall Survival [Time Frame: From Randomization (11 December 2006) until approximately 78% overall survival events at the time of the second overall survival update (3 March 2010) (up to 168.29 weeks)]

Time to Response [Time Frame: From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)]

Response [Time Frame: From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)]

Safety and Tolerability of Pazopanib, Lapatinib and the Combination of Pazopanib and Lapatinib [Time Frame: From Randomization (11 December 2006) until last participant had last visit (28 July 2011) in combined population of two monotherapy arms (up to 241.43 weeks)]

Duration of Response [Time Frame: From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)]

Secondary ID(s)

VEG105281

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 14/03/2011
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00430781