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A Phase I Combination of Pazopanib and Carboplatin in Advanced Solid Malignancies

Phase 1
18 Years
Open (Enrolling)
Cancer, Metastatic

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Trial Information

A Phase I Combination of Pazopanib and Carboplatin in Advanced Solid Malignancies

Pazopanib has shown a promising anti-cancer activity as a single agent tyrosine kinase
inhibitor. Activity against multiple tumors such as renal cell carcinoma (RCC) and
neuroendocrine tumors have been documented, and it recently gained FDA approval for the
treatment of metastatic kidney cancer. Also, an impressive activity as a single agent was
recently reported in non-small cell lung cancer (NSCLC) in the neoadjuvant setting, where
tumor shrinkage occurred in 86% of patients. Encouraging activity has also been seen in
cervical cancer, ovarian cancer and soft tissue sarcomas. Multi-kinase targeting is an
approach that may prove beneficial in a number of patient populations. In particular cancers
such as breast, colon, pancreas etc., patients represent heterogeneous population of small
groups based on genetic analyses. Some of these populations may benefit when multiple agents
are given which have similar, but distinct targets of action. Dosages and therefore
associated toxicities might be reduced by such an approach.

Inclusion Criteria:

- 18 years of age or older

- Histologically confirmed advanced solid tumor type that is FDA approved for treatment
with Carboplatin.

- Life expectancy at least 12 wks

- ECOG performance status of 0-2

- Provide written informed

- Adequate organ system function


- Non-childbearing potential, who has had:

- A hysterectomy

- A bilateral oophorectomy (ovariectomy)

- A bilateral tubal ligation

- Is post-menopausal

- Complete abstinence from sexual intercourse 14 days before, during and at least 21
days after the last dose of investigational product

- Oral contraceptive

- Injectable progestogen

- Implants of levonorgestrel

- Estrogenic vaginal ring

- Percutaneous contraceptive patches

- Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate
of less than 1% per year

- Sole male partner sterilization prior to the female subject's entry - Double barrier
method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal
spermicidal agent (foam/ gel/ film/cream/suppository)

- If lactating: discontinue nursing prior to the first dose, during and for 14 days
following the last dose of study drug

Exclusion Criteria:

- History or clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS
metastases, are asymptomatic, and have had no requirement for steroids or
anti-seizure medication for 6 months prior to first dose of study drug.

- Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance
imaging [MRI]) is required only if clinically indicated or if the subject has a
history of CNS metastases.

- 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.

- Presence of uncontrolled infection

- Corrected QT interval (QTc) > 480 msecs using Bazett's formula

- 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)

- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of greater
than or equal to 140 mmHg or diastolic blood pressure (DBP) of greater than or equal
to 90mmHg]

Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to
study entry.

- 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

- Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
presence of any non-healing wound, fracture, or ulcer (procedures such as catheter
placement not considered to be major)

- Evidence of active bleeding or bleeding diathesis

- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

- Hemoptysis within 8 weeks of 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 with study procedures

- Treatment with any of the following anti-cancer therapies:

- Radiation therapy, surgery or tumor embolization within 14 days prior to the first
dose of pazopanib OR

- Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal
therapy within 14 days or five half-lives of a drug (whichever is longer) prior to
the first dose of pazopanib

- Any ongoing toxicity from prior anti-cancer therapy that is greater than Grade 1
and/or that is progressing in severity, except alopecia

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of Pazopanib when used in combination with Carboplatin

Outcome Description:

Patients will receive 200mg of Pazopanib, with later subjects receiving higher dosages up to 800mg of Pazopanib. If a given dose level is not well tolerated when given on all days (1-21) of each cycle, the study will no longer use that dosage. Later subjects may take Pazopanib from days 3-19 of the three week cycle to see if that dosing schedule is better tolerated. If patients experience side effects from Pazopanib or tests indicate some undesirable effects, then the dose level of Pazopanib that they are receiving may need to be adjusted, with increased monitoring.

Outcome Time Frame:

3 months

Safety Issue:


Principal Investigator

Montasur Shaheen, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

New Mexico Cancer Care Alliance/UNMCC


United States: Food and Drug Administration

Study ID:

INST 1015



Start Date:

August 2012

Completion Date:

August 2017

Related Keywords:

  • Cancer, Metastatic
  • Metastatic
  • carboplatin
  • Paraplatin
  • Pazopanib
  • Votrient
  • Alkylating agent
  • Tyrosine kinase inhibitor
  • Metastatic disease



University of New Mexico Cancer Center Albuquerque, New Mexico  87131-5636