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

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

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer
• Interventions: Drug: Gedatolisib; Drug: Paclitaxel; Drug: Carboplatin
• Enrollment: 3

Participant Flow

Recruitment Details	Recruitment period was from 9/25/2017 until 12/06/2018, at which point the study was closed due to low accrual.
Pre-assignment Details

Arm/Group Title	Treatment Arm (Phase 1b; Dose Level 1)	Treatment Arm (Phase 1b; Dose Level 2)	Treatment Arm (Phase 1b; Dose Level 3)	Treatment Arm (Phase 2)
Arm/Group Description	Gedatolisib (Dose level 1[110 mg]), Paclitaxel, and Carboplatin 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. 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.	Gedatolisib (Dose level 2[150 mg]), Paclitaxel, and Carboplatin 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. 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.	Gedatolisib (Dose level 2[180 mg]), Paclitaxel, and Carboplatin 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. 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.	Gedatolisib (MTD From the Phase 1b portion), Paclitaxel, and Carboplatin 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. 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.
Period Title: Overall Study
Started	3	0	0	0
Completed	1	0	0	0
Not Completed	2	0	0	0
Reason Not Completed
Death	1	0	0	0
Withdrawal by Subject	1	0	0	0

Baseline Characteristics

Arm/Group Title		Treatment Arm
Arm/Group Description		Gedatolisib, Paclitaxel, and Carboplatin 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. Dose Level 1: 110 mg Dose Level 2: 150 mg Dose Level 3: 180 mg 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. 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.
Overall Number of Baseline Participants		3
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	1 33.3%
	>=65 years	2 66.7%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants
	Female	2 66.7%
	Male	1 33.3%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	3 100.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	3 100.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	3 participants
		3

Outcome Measures

1. Primary Outcome

Title	Dose Tolerability
Description	To identify the maximum tolerated dose of PF-05212384 in combination with paclitaxel and carboplatin in subjects with NSCLC.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Data are not reported for this outcome measure because an insufficient number of participants were evaluable to determine the MTD.

Arm/Group Title	Treatment Arm
Arm/Group Description:	Gedatolisib, Paclitaxel, and Carboplatin 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. Dose Level 1: 110 mg Dose Level 2: 150 mg Dose Level 3: 180 mg 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. 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.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

2. Primary Outcome

Title	Objective Response Rate (ORR)
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The sample of only 1 evaluable subject was not sufficient to analyze this outcome measure.

Arm/Group Title	Treatment Arm
Arm/Group Description:	Gedatolisib, Paclitaxel, and Carboplatin 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. Dose Level 1: 110 mg Dose Level 2: 150 mg Dose Level 3: 180 mg 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. 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.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	Adverse event data was collected from the time a subject signed consent until 28 days after the last dose of study treatment. During this time frame, adverse event data was collected at the time informed consent was signed, on day 1 of each treatment cycle, and 28 days after the last dose of study treatment at a minimum. The time over which adverse event data was collected for the 2 subjects for whom adverse event data was collected was 2.6 and 5.75 months.
Adverse Event Reporting Description	Adverse events were assessed by the principal investigator, the treating sub-investigator, and/or the study coordinator from the time a subject signed consent until 28 days after the last dose of study treatment. During this time frame, adverse event data was collected at the time informed consent was signed, on day 1 of each treatment cycle, and 28 days after the last dose of study treatment at a minimum. Adverse events were assessed by physical examination, labs, and subject self-reports.
Arm/Group Title	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)
Arm/Group Description	Gedatolisib, Paclitaxel, and Carboplatin 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 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. 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.		Gedatolisib, Paclitaxel, and Carboplatin 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 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. 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.		Gedatolisib, Paclitaxel, and Carboplatin 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 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. 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.		Gedatolisib, Paclitaxel, and Carboplatin 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 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. 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.
All-Cause Mortality
	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)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	1/3 (33.33%)		0/0		0/0		0/0
Serious Adverse Events
	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)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.33%)		0/0		0/0		0/0
Infections and infestations
Sepsis † 1 [1]	1/3 (33.33%)	1	/0		/0		/0
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment; [1] Grade 4 Sepsis
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	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)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0.00%)		0/0		0/0		0/0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Protocol Development Manager
• Organization: University of Florida Heath Cancer Center
• Phone: 352-273-8128
• EMail: clh1230@ufl.edu

• 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 Submitted: September 27, 2016
• First Posted: September 30, 2016
• Results First Submitted: July 16, 2019
• Results First Posted: October 3, 2019
• Last Update Posted: October 4, 2019