Non-Small Cell Lung CancerPhase 1/2NCT02920450
Study of Paclitaxel, Carboplatin, and PF-05212384 in Advanced or Metastatic NSCLC (UF-STO-LUNG-002)
A Phase 1/2 study testing Gedatolisib, Paclitaxel and Carboplatin in people with Non-Small Cell Lung Cancer, run by University of Florida at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Gedatolisib, Paclitaxel and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Sep 2017to 4 Apr 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Gedatolisib, Paclitaxel, Carboplatin
- Keywords
- lung, carcinoma
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GedatolisibDrug
Also called PF-05212384
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
PaclitaxelDrug
Also called Taxol®, NSC-673089
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.
CarboplatinDrug
Also called CBDCA, NSC-241240
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm (Phase 1b; Gedatolisib Dose Level 1[110 mg]) | Experimental | Not described Receives: Drug: Gedatolisib; Drug: Paclitaxel; Drug: Carboplatin |
| Treatment Arm (Phase 1b; Gedatolisib Dose Level 2[150 mg]) | Experimental | Not described Receives: Drug: Gedatolisib; Drug: Paclitaxel; Drug: Carboplatin |
| Treatment Arm (Phase 1b; Gedatolisib Dose Level 3[180 mg]) | Experimental | Not described Receives: Drug: Gedatolisib; Drug: Paclitaxel; Drug: Carboplatin |
| Treatment Arm (Phase 2; MTD of Gedatolisib from Phase Ib) | Experimental | Not described Receives: Drug: Gedatolisib; Drug: Paclitaxel; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Tolerability
To identify the maximum tolerated dose of PF-05212384 in combination with paclitaxel and carboplatin in subjects with NSCLC.
Measured: 1 year
Objective Response Rate (ORR)
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2016 (estimated)
- Study start25 Sep 2017
- Primary completion2 Jan 2019
- Study completion4 Apr 2019
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Dennie Jones, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02920450
- Sponsor's protocol ID
- IRB201601181 -A
- Other IDs
- WI211924, UF-STO-LUNG-002, OCR15075
- Status last verified
- Oct 2019
- First submitted
- 27 Sep 2016
- Last updated
- 4 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02920450
- Acronym / sponsor ID
- IRB201601181 -A
- Conditions
- Non-Small Cell Lung Cancer
- Keywords
- lung, carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 25 Sep 2017 (actual)
- Primary completion
- 2 Jan 2019 (actual)
- Study completion
- 4 Apr 2019 (actual)
- First posted
- 30 Sep 2016 (estimated)
- Results
- Posted 3 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm (Phase 1b; Gedatolisib Dose Level 1[110 mg]) | Experimental | Drug: Gedatolisib, Drug: Paclitaxel, Drug: Carboplatin |
| Treatment Arm (Phase 1b; Gedatolisib Dose Level 2[150 mg]) | Experimental | Drug: Gedatolisib, Drug: Paclitaxel, Drug: Carboplatin |
| Treatment Arm (Phase 1b; Gedatolisib Dose Level 3[180 mg]) | Experimental | Drug: Gedatolisib, Drug: Paclitaxel, Drug: Carboplatin |
| Treatment Arm (Phase 2; MTD of Gedatolisib from Phase Ib) | Experimental | Drug: Gedatolisib, Drug: Paclitaxel, Drug: Carboplatin |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GedatolisibAlso: PF-05212384During 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 | Drug | Treatment Arm (Phase 1b; Gedatolisib Dose Level 1[110 mg]), Treatment Arm (Phase 1b; Gedatolisib Dose Level 2[150 mg]), Treatment Arm (Phase 1b; Gedatolisib Dose Level 3[180 mg]), Treatment Arm (Phase 2; MTD of Gedatolisib from Phase Ib) |
| PaclitaxelAlso: Taxol®, NSC-673089Given 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. | Drug | Treatment Arm (Phase 1b; Gedatolisib Dose Level 1[110 mg]), Treatment Arm (Phase 1b; Gedatolisib Dose Level 2[150 mg]), Treatment Arm (Phase 1b; Gedatolisib Dose Level 3[180 mg]), Treatment Arm (Phase 2; MTD of Gedatolisib from Phase Ib) |
| CarboplatinAlso: CBDCA, NSC-241240The 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. | Drug | Treatment Arm (Phase 1b; Gedatolisib Dose Level 1[110 mg]), Treatment Arm (Phase 1b; Gedatolisib Dose Level 2[150 mg]), Treatment Arm (Phase 1b; Gedatolisib Dose Level 3[180 mg]), Treatment Arm (Phase 2; MTD of Gedatolisib from Phase Ib) |
Primary outcome
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dennie Jones, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Gedatolisib, Paclitaxel and Carboplatin in people with Non-Small Cell Lung Cancer, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Tolerability (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2019.