Study of Paclitaxel, Carboplatin, and PF-05212384 in Advanced or Metastatic NSCLC (UF-STO-LUNG-002)



Status:Active, not recruiting
Conditions:Lung Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - 90
Updated:1/23/2019
Start Date:September 25, 2017
End Date:February 2020

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A Non-Randomized Phase Ib-II Protocol of Paclitaxel, Carboplatin and the Dual PI3K/mTOR Kinase Inhibitor, PF-05212384, for Patients With Advanced, or Metastatic Non-Small Cell Carcinoma of the Lung

The purpose of this research study is to determine if the study drug, Gedatolisib
(PF-05212384), given in combination with paclitaxel and carboplatin will work against
unresectable non-small cell lung cancer.

Approximately 70% of patients with unresectable non-small cell lung cancer (NSCLC) who
receive and progress through frontline chemotherapy will be eligible for second line
treatments. Any of the agents which are available for frontline therapy can be used in the
salvage setting, though only erlotinib, docetaxel, and pemetrexed (in non-squamous cell
carcinoma) are FDA-approved in the salvage setting based upon their demonstrated survival
benefit in randomized phase III trials. All three appear to be roughly equivalent in terms of
clinical benefit, which is admittedly modest, with response rates <10%, clinical benefit
rates of approximately 50%, and overall survivals of approximately 6 months. Still, a
substantial number of patients may not benefit from the agents in the salvage treatment
setting, thus it is critical to identify those patients who stand to benefit the most.

The study will consist of two phases, Ib and II. The phase Ib portion will study dose
escalations in separate 3+3 cohorts using escalating doses of PF-05212384. The phase II
portion will consist of a two stage Simon design. The doses for paclitaxel (200 mg/m2, Q21
days) and carboplatin (AUC=6, Q21 days) do not adjust as part of the study design. The dose
of PF-05212384 will be determined during the Phase Ib portion.

The primary endpoint of the phase Ib portion of this protocol is to determine a tolerable
phase II dose of PF-05212384 in combination with paclitaxel and carboplatin. The primary
endpoint of the phase II portion of this study is to determine the objective response rate of
disease to the administration of PF-05212384 in combination with paclitaxel and carboplatin.
A secondary endpoint of this study will be progression-free survival following PF-05212384
therapy.

Inclusion Criteria:

- Signed Institutional Review Board (IRB)-approved informed consent prior to any
study-related procedures

- Age of 18 years or older

- Advanced-stage unresectable NSCLC, as confirmed by pathological and/or radiological
analysis (subjects will be classified as having advanced disease if they were not
eligible for, or had disease progression after, surgical or locoregional therapies)

- Prior chemotherapy will be allowed for other invasive malignancies, provided therapy
was completed at least five years before the start of protocol therapy, and
participants have recovered from all toxicities of that prior therapy

- Participants may have received prior chemotherapy for NSCLC

- In the Phase II portion, subjects must have disease which lacks PTEN expression by
immunohistochemistry, or has known prior activating PI3K or inactivating PTEN gene
mutations (mutations will not be assayed for specifically)

- Eastern Cooperative Oncology Group (ECOG) performance status score < 2

- Life expectancy ≥ 12 week

- Participants must have measureable disease by RECIST criteria

- Absolute neutrophil count > 1500 mm3 (individuals with benign ethnic neutropenia may
be enrolled if they have no evidence of infectious diathesis, or febrile neutropenia
at the time of enrollment)

- Platelet count ≥ 100×109 L

- Hgb ≥ 8.5 g/dL (subjects may receive transfusions to achieve this, in the absence of
overt bleeding)

- Total Bilirubin ≤ 2 mg/dL

- aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤ 3 times the upper
limit of normal range

- Serum creatinine ≤1.5 times the upper limit of the normal range

- Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for at least 6 months after
the last dose of study drug to minimize the risk of pregnancy. Prior to study
enrollment, women of childbearing potential must be advised of the importance of
avoiding pregnancy during trial participation and the potential risk factors for an
unintentional pregnancy. WOCBP include any woman who has experienced menarche and who
has not undergone successful surgical sterilization (hysterectomy, bilateral tubal
ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is
defined as:

- Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or

- For women with irregular menstrual periods who are taking hormone replacement therapy
(HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35
mIU/mL.

- Males with female partners of child-bearing potential must agree to use
physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy)
throughout the study and should avoid conceiving children for 6 months following the
last dose of study drug

Exclusion Criteria:

- Uncontrolled cardiac disease, congestive heart failure, angina, arrhythmias or
hypertension.

- Myocardial infarction or unstable angina within 2 months of treatment.

- Known human immunodeficiency virus (HIV) infection or chronic active Hepatitis B
(subjects will not be screened for this).

- Active clinically serious infection > CTCAE Grade 2.

- Thrombotic or embolic events such as a cerebrovascular accident including transient
ischemic attacks within the past 6 months.

- Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of
study drug.

- Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of
study drug.

- Serious non-healing wound, ulcer, or bone fracture.

- Evidence or history of bleeding diathesis or coagulopathy

- Major surgery, open biopsy or significant traumatic injury within 4 weeks of first
study drug

- Women or men of childbearing potential who are unwilling or unable to use an
acceptable method to avoid pregnancy for the entire study period and for at least 6
months after the last dose of study drug

- Women who are pregnant or breastfeeding.

- History of any other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of protocol therapy or that might affect the interpretation of
the results of the study or that puts the subject at high risk for treatment
complications, in the opinion of the treating physician.

- Prisoners or subjects who are involuntarily incarcerated.

- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical illness.

- Subjects demonstrating an inability to comply with the study and/or follow-up
procedures.
We found this trial at
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Gainesville, Florida 32610
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Gainesville, FL
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