Phase II Study of Pazopanib and Topotecan in Cervical Cancer

NCT02348398 | Withdrawn Phase 2

• 2 other identifiers: 2014-0625NCI-2015-00211
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical research study is to learn if the combination of topotecan and pazopanib can help to control recurrent cervical cancer. The safety of the study drug combination will also be studied.

Conditions

Cervical Cancer

Keywords

Cervical Cancer; Recurrent cervical cancer; Squamous cervical cancer; Adenocarcinoma of the cervix; Adenosquamous cervical cancer; Persistent cervical cancer; Pazopanib; GW786034; Topotecan; Hycamtin

Outcome Measures

Primary Outcomes (1)

• Objective Tumor Response

  Duration of overall response measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Duration of overall CR is measured from the time measurement criteria are first met for CR until first date that recurrent disease is objectively documented. Complete Response (CR): Disappearance of all target lesions. Any pathologic lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

  6 months

Study Arms (1)

Pazopanib + Topotecan

EXPERIMENTAL

Pazopanib 600 mg taken orally continuously while Topotecan 0.25 mg taken orally for 21 days continuously followed by 7 days off. A cycle will be defined as 28 days. During follow up if disease gets worse, participant called by study staff every 3 months.

Drug: Pazopanib; Drug: Topotecan; Behavioral: Phone Call

Interventions

Pazopanib DRUG

600 mg by mouth daily in a 28 day cycle.

Also known as: GW786034

Pazopanib + Topotecan

Topotecan DRUG

0.25 mg by mouth daily for 21 days of a 28 day cycle.

Also known as: Hycamtin

Pazopanib + Topotecan

Phone Call BEHAVIORAL

During follow up if disease gets worse, participant called by study staff every 3 months. Each call should last about 5 minutes.

Pazopanib + Topotecan

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed diagnosis of recurrent, persistent or advanced (stage IVB) squamous, adenocarcinoma or adenosquamous cervical cancer.
• Eastern Cooperative Oncology Group (ECOG) performance status of \</= 2.
• Measurable disease criteria as defined by RECIST 1.1 criteria, measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be greater than or equal to 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray. Lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT or MRI.
• Patients with persistent or recurrent disease must have received definitive chemoradiation therapy as first line therapy. Patients with advanced (stage IVB) disease may have received palliative radiation therapy.
• Patients may have received one prior chemotherapy regimen for recurrence or progression. Cisplatinum with concurrent radiation does not count as a prior chemotherapy. Prior treatment with bevacizumab is allowable.
• Patients must have adequate: Bone Marrow Function: Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl. Platelets greater than or equal to 100,000/mcl. Hemoglobin greater than or equal to 9 g/dL. Blood coagulation parameters: PT such that the international normalized ratio (INR) is less than or equal to 1.2 x ULN (institutional upper limit of normal) (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a PTT less than or equal to 1.2 x ULN. Subjects receiving anticoagulant therapy are eligible if their INR is stable and PT/PTT therapeutic and within the recommended range for the desired level of anticoagulation. Hepatic function: Bilirubin less than or equal to 1.5 x ULN AST and ALT less than or equal to 2.5 x ULN and alkaline phosphatase less than or equal to 2.5 x ULN. Renal function: Creatinine less than or equal to 1.5 x ULN.
• Continue from #6. Urine Protein: If urine protein to creatinine ratio is greater than or equal to 1, a 24 hour urine protein must be assessed. Subjects must have a 24 hour urine protein value less than 1 g to be eligible. Use of urine dipstick for renal function assessment is not acceptable. Thyroid function: Patients must have normal baseline thyroid function tests (TSH, T3, T4). A history of hypothyroidism and/or hyperthyroidism is allowed, as long as the patient has stable well-controlled thyroid function for a minimum of 2 months. Neurologic function: Neuropathy (sensory or motor) less than or equal to grade 1.
• Recovery from effects of recent surgery, radiotherapy, or chemotherapy Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated UTI). Any other prior therapy such as radiation therapy, tumor embolization, chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormone therapy, must be discontinued at least 28 days prior to the first dose of pazopanib. At least 28 days must have elapsed since the patient underwent any major surgery (laparotomy, laparoscopy, thoracotomy, video assisted thorascopic surgery-VATS). No restriction on minor procedures (central venous access catheter placement, ureteral stent placement, thoracentesis).
• Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception. Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects.
• Patients must have signed an approved informed consent and authorization form permitting the release of personal health information.
• Patients must be greater than or equal to 18 years of age.
• Patients must be capable of taking and absorbing oral medications. A patient must be clear of the following: Any lesion, whether induced by tumor, radiation or other conditions, which makes it difficult to swallow tablets Prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel. Active peptic ulcer disease. Malabsorption syndrome
• Any concomitant medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes should be discontinued or replaced with drugs that do not carry these risks, if possible. Patients who must take medication with a possible risk of Torsades de Pointes should be watched carefully for symptoms of QTc prolongation, such as syncope. Patients with personal or family history of congenital long QTc syndrome are NOT eligible.
• Patients must meet pre-entry requirements.

You may not qualify if:

• Patients who have had previous treatment with Pazopanib or Topotecan.
• Prior malignancy. Note: Subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
• Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 6 monthly time interval.
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: Active peptic ulcer disease.Known intraluminal metastatic lesion/s with risk of bleeding. Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation. History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: Malabsorption syndrome. Major resection of the stomach or small bowel.
• Corrected QT interval (QTc) \> 480 msecs.
• History of any one or more of the following cardiovascular conditions within the past 6 months:Cardiac angioplasty or stenting. Myocardial infarction. Unstable angina. Coronary artery bypass graft surgery. Symptomatic peripheral vascular disease. Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA).
• Uncontrolled hypertension \[defined as systolic blood pressure (SBP) of \>/= 140 mmHg or diastolic blood pressure (DBP) of \>/= 90mmHg\].
• History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.
• Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer.
• Evidence of active bleeding or pathologic conditions that carry high risk of bleeding such as known bleeding disorders, coagulopathy or tumor involving major vessels.
• Recent hemoptysis (\>/=½ teaspoon of red blood within 8 weeks before first dose of study drug).
• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
• Unable or unwilling to discontinue use of prohibited medications for at least 28 days prior to the first dose of topotecan/pazopanib and for the duration of the study.
• Administration of any non-oncologic investigational drug within 30 days prior to receiving the first dose of topotecan/pazopanib.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• GlaxoSmithKline: collaborator

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

pazopanib; Topotecan

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Michael M. Frumovitz, MD, MPH

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2015
• First Posted: January 28, 2015
• Study Start: August 1, 2016
• Primary Completion: August 1, 2019
• Last Updated: August 16, 2016

Record last verified: 2016-08