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

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ClinicalTrials.gov Identifier: NCT02920450
Recruitment Status : Terminated (Slow accrual)
First Posted : September 30, 2016
Results First Posted : October 3, 2019
Last Update Posted : October 4, 2019
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University of Florida

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Gedatolisib Drug: Paclitaxel Drug: Carboplatin Phase 1 Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 25, 2017
Actual Primary Completion Date : January 2, 2019
Actual Study Completion Date : April 4, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment Arm (Phase 1b; Gedatolisib Dose Level 1[110 mg]) Drug: Gedatolisib

During the first phase, subjects will be sequentially enrolled to each increasing dose level, beginning with dose level 1 (110 mg) until the first dose limiting toxicity occurs, or safely accrued to dose level 3. PF-05212384 is intravenously infused over a thirty minute period. The dose given in the phase 2 portion will be the MTD determined in the phase Ib portion of the study.

Dose Level 1: 110 mg Dose Level 2: 150 mg Dose Level 3: 180 mg

Other Name: PF-05212384

Drug: Paclitaxel
Given as 200 mg/m2 infusion over a three hour period at every twenty-one days; the dose will not adjust as part of the study design.
Other Names:
  • Taxol®
  • NSC-673089

Drug: Carboplatin
The carboplatin dose (mg) = AUC x (CrCl + 25) where AUC = 6 depending on the dose level. carboplatin is intravenously infused over a thirty minute period following paclitaxel administration; the dose will not adjust as part of the study design.
Other Names:
  • CBDCA
  • NSC-241240

Experimental: Treatment Arm (Phase 1b; Gedatolisib Dose Level 2[150 mg]) Drug: Gedatolisib

During the first phase, subjects will be sequentially enrolled to each increasing dose level, beginning with dose level 1 (110 mg) until the first dose limiting toxicity occurs, or safely accrued to dose level 3. PF-05212384 is intravenously infused over a thirty minute period. The dose given in the phase 2 portion will be the MTD determined in the phase Ib portion of the study.

Dose Level 1: 110 mg Dose Level 2: 150 mg Dose Level 3: 180 mg

Other Name: PF-05212384

Drug: Paclitaxel
Given as 200 mg/m2 infusion over a three hour period at every twenty-one days; the dose will not adjust as part of the study design.
Other Names:
  • Taxol®
  • NSC-673089

Drug: Carboplatin
The carboplatin dose (mg) = AUC x (CrCl + 25) where AUC = 6 depending on the dose level. carboplatin is intravenously infused over a thirty minute period following paclitaxel administration; the dose will not adjust as part of the study design.
Other Names:
  • CBDCA
  • NSC-241240

Experimental: Treatment Arm (Phase 1b; Gedatolisib Dose Level 3[180 mg]) Drug: Gedatolisib

During the first phase, subjects will be sequentially enrolled to each increasing dose level, beginning with dose level 1 (110 mg) until the first dose limiting toxicity occurs, or safely accrued to dose level 3. PF-05212384 is intravenously infused over a thirty minute period. The dose given in the phase 2 portion will be the MTD determined in the phase Ib portion of the study.

Dose Level 1: 110 mg Dose Level 2: 150 mg Dose Level 3: 180 mg

Other Name: PF-05212384

Drug: Paclitaxel
Given as 200 mg/m2 infusion over a three hour period at every twenty-one days; the dose will not adjust as part of the study design.
Other Names:
  • Taxol®
  • NSC-673089

Drug: Carboplatin
The carboplatin dose (mg) = AUC x (CrCl + 25) where AUC = 6 depending on the dose level. carboplatin is intravenously infused over a thirty minute period following paclitaxel administration; the dose will not adjust as part of the study design.
Other Names:
  • CBDCA
  • NSC-241240

Experimental: Treatment Arm (Phase 2; MTD of Gedatolisib from Phase Ib) Drug: Gedatolisib

During the first phase, subjects will be sequentially enrolled to each increasing dose level, beginning with dose level 1 (110 mg) until the first dose limiting toxicity occurs, or safely accrued to dose level 3. PF-05212384 is intravenously infused over a thirty minute period. The dose given in the phase 2 portion will be the MTD determined in the phase Ib portion of the study.

Dose Level 1: 110 mg Dose Level 2: 150 mg Dose Level 3: 180 mg

Other Name: PF-05212384

Drug: Paclitaxel
Given as 200 mg/m2 infusion over a three hour period at every twenty-one days; the dose will not adjust as part of the study design.
Other Names:
  • Taxol®
  • NSC-673089

Drug: Carboplatin
The carboplatin dose (mg) = AUC x (CrCl + 25) where AUC = 6 depending on the dose level. carboplatin is intravenously infused over a thirty minute period following paclitaxel administration; the dose will not adjust as part of the study design.
Other Names:
  • CBDCA
  • NSC-241240




Primary Outcome Measures :
  1. Dose Tolerability [ Time Frame: 1 year ]
    To identify the maximum tolerated dose of PF-05212384 in combination with paclitaxel and carboplatin in subjects with NSCLC.

  2. Objective Response Rate (ORR) [ Time Frame: 1 year ]
    To estimate the objective rate of response of PF-05212384 in combination with paclitaxel and carboplatin administered to subjects with unresectable or metastatic NSCLC, according to current RECIST criteria. ORR is defined as the number of participants who achieved either a partial or complete response by RECIST 1.1 criteria. By these criteria, Complete Response (CR) is defined as the disappearance of all target lesions and Partial Response (PR) is defined as a decrease of at least 30% in the sum of the longest diameter of the target lesions.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02920450


Locations
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United States, Florida
UF Health Cancer Center
Gainesville, Florida, United States, 32608
Sponsors and Collaborators
University of Florida
Pfizer
Investigators
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Principal Investigator: Dennie Jones, MD University of Florida
  Study Documents (Full-Text)

Documents provided by University of Florida:
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Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02920450    
Other Study ID Numbers: IRB201601181 -A
WI211924 ( Other Identifier: Pfizer Inc. )
UF-STO-LUNG-002 ( Other Identifier: University of Florida )
OCR15075 ( Other Identifier: University of Florida )
First Posted: September 30, 2016    Key Record Dates
Results First Posted: October 3, 2019
Last Update Posted: October 4, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Florida:
lung
carcinoma
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Paclitaxel
Carboplatin
Gedatolisib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors