Trial Outcomes & Findings for Temsirolimus and Pemetrexed for Recurrent or Refractory Non-Small Cell Lung Cancer (NCT NCT00921310)

NCT ID: NCT00921310

Last Updated: 2016-12-13

Results Overview

The starting dose and schedule of pemetrexed will be 500 mg/m2 given every 3 weeks and the starting dose for temsirolimus will be 15 mg given weekly for 3 weeks, to complete 1 cycle. In subsequent cohorts, dose will be escalated or de-escalated. Enrollment to each cohort is based on toxicity experienced at that dose level. The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort experience dose-limiting toxicity during the first cycle. Six patients will be enrolled at the maximum tolerated dose to ensure that no more than 2 DLTs occur at the MTD. Dose escalations will proceed until the MTD has been reached.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Completion of first cycle by all enrolled patients in Phase I portion of study

Results posted on

2016-12-13

Participant Flow

The study opened to participant enrollment on 09/28/2009 and closed to participant enrollment on 12/20/2011.

Participant milestones

Participant milestones
Measure
Phase I Dose Level 1 (Pemetrexed & Temsirolimus)
* Pemetrexed 500mg/m\^2 intravenous (IV) on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle
Phase I Dose Level -1 (Pemetrexed & Temsirolimus)
* Pemetrexed (375 mg/m\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
* Phase 2 dose will be the maximum tolerated dose found in the Phase I portion of the study. * Pemetrexed (375 mg/m\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Overall Study
STARTED
2
6
4
Overall Study
COMPLETED
2
6
4
Overall Study
NOT COMPLETED
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Temsirolimus and Pemetrexed for Recurrent or Refractory Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Phase I (Premetrexed & Temsirolimus)
n=8 Participants
* Participants enrolled in the Phase I portion Dose Level 1 received: * Pemetrexed 500mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle * Participants enrolled in the Phase I portion Dose Level -1 received: * Pemetrexed 375mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
n=4 Participants
-Participants enrolled in the Phase 2 portion received: * Pemetrexed (375 mg/m2\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Total
n=12 Participants
Total of all reporting groups
Age, Continuous
58.5 years
n=5 Participants
67.5 years
n=7 Participants
62.5 years
n=5 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
2 Participants
n=7 Participants
4 Participants
n=5 Participants
Sex: Female, Male
Male
6 Participants
n=5 Participants
2 Participants
n=7 Participants
8 Participants
n=5 Participants
Region of Enrollment
United States
8 participants
n=5 Participants
4 participants
n=7 Participants
12 participants
n=5 Participants

PRIMARY outcome

Timeframe: Completion of first cycle by all enrolled patients in Phase I portion of study

The starting dose and schedule of pemetrexed will be 500 mg/m2 given every 3 weeks and the starting dose for temsirolimus will be 15 mg given weekly for 3 weeks, to complete 1 cycle. In subsequent cohorts, dose will be escalated or de-escalated. Enrollment to each cohort is based on toxicity experienced at that dose level. The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort experience dose-limiting toxicity during the first cycle. Six patients will be enrolled at the maximum tolerated dose to ensure that no more than 2 DLTs occur at the MTD. Dose escalations will proceed until the MTD has been reached.

Outcome measures

Outcome measures
Measure
Phase I (Premetrexed & Temsirolimus)
n=8 Participants
* Participants enrolled in the Phase I portion Dose Level 1 received: * Pemetrexed 500mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle * Participants enrolled in the Phase I portion Dose Level -1 received: * Pemetrexed 375mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
-Participants enrolled in the Phase 2 portion received: * Pemetrexed (375 mg/m2\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
* Phase 2 dose will be the maximum tolerated dose found in the Phase I portion of the study. * Pemetrexed (375 mg/m\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Phase I Only: Maximum Tolerated Dose (MTD) of Pemetrexed That Could be Administered Weekly in Combination With Temsirolimus
375 mg/m^2

PRIMARY outcome

Timeframe: Completion of first cycle by all enrolled patients in Phase I portion of study

The starting dose and schedule of pemetrexed will be 500 mg/m2 given every 3 weeks and the starting dose for temsirolimus will be 15 mg given weekly for 3 weeks, to complete 1 cycle. In subsequent cohorts, dose will be escalated or de-escalated. Enrollment to each cohort is based on toxicity experienced at that dose level. The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort experience dose-limiting toxicity during the first cycle. Six patients will be enrolled at the maximum tolerated dose to ensure that no more than 2 DLTs occur at the MTD. Dose escalations will proceed until the MTD has been reached.

Outcome measures

Outcome measures
Measure
Phase I (Premetrexed & Temsirolimus)
n=8 Participants
* Participants enrolled in the Phase I portion Dose Level 1 received: * Pemetrexed 500mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle * Participants enrolled in the Phase I portion Dose Level -1 received: * Pemetrexed 375mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
-Participants enrolled in the Phase 2 portion received: * Pemetrexed (375 mg/m2\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
* Phase 2 dose will be the maximum tolerated dose found in the Phase I portion of the study. * Pemetrexed (375 mg/m\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Phase I Only: Maximum Tolerated Dose (MTD) of Temsirolimus That Could be Administered Weekly in Combination With Pemetrexed
15 mg

PRIMARY outcome

Timeframe: Completion of first cycle (approximately 21 days)

DLT will be defined as occurring within the first cycle of Phase I only and will be graded according to the Common Terminology Criteria for Adverse Events v 3.0 (CTCAE) * Any grade 3 or higher hematologic toxicity with the exception of anemia. * Any grade 3 or higher non-hematologic toxicity related to study therapy (except alopecia). * Grade 3 or 4 pneumonitis or esophagitis. * Treatment delay of temsirolimus for more than 14 consecutive days due to study-related toxicity. * Treatment delay of pemetrexed therapy for more than 14 consecutive days because of study-related toxicity.

Outcome measures

Outcome measures
Measure
Phase I (Premetrexed & Temsirolimus)
n=2 Participants
* Participants enrolled in the Phase I portion Dose Level 1 received: * Pemetrexed 500mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle * Participants enrolled in the Phase I portion Dose Level -1 received: * Pemetrexed 375mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
n=6 Participants
-Participants enrolled in the Phase 2 portion received: * Pemetrexed (375 mg/m2\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
* Phase 2 dose will be the maximum tolerated dose found in the Phase I portion of the study. * Pemetrexed (375 mg/m\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Phase I Only: Number of Participants Who Experience Dose-limiting Toxicities (DLT) of Temsirolimus and Pemetrexed
2 participants
0 participants

PRIMARY outcome

Timeframe: 2 years

Population: (4) patients in Phase 1 were not evaluable for response as they were removed from study prior to week 6 scans. One patient in Phase 2 was not evaluable due to expiring prior to week 6 scans.

* Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. * Complete response (CR)-disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR)-at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD

Outcome measures

Outcome measures
Measure
Phase I (Premetrexed & Temsirolimus)
n=4 Participants
* Participants enrolled in the Phase I portion Dose Level 1 received: * Pemetrexed 500mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle * Participants enrolled in the Phase I portion Dose Level -1 received: * Pemetrexed 375mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
n=3 Participants
-Participants enrolled in the Phase 2 portion received: * Pemetrexed (375 mg/m2\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
* Phase 2 dose will be the maximum tolerated dose found in the Phase I portion of the study. * Pemetrexed (375 mg/m\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Phase I and Phase II: Overall Response Rate (Complete Response + Partial Response)
0 percentage of participants
33.3 percentage of participants

PRIMARY outcome

Timeframe: Cycle 1 Day 1, one hour post completion of initial temsirolimus dose, and Cycle 1 Day 8

Population: Due to early termination of the study by withdrawal of funding by sponsor (Pfizer merged with Wyeth), the peripheral blood samples that were collected for this outcome measure were not analyzed prior to losing funding.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Cycle 1 Day 1, one hour post completion of initial temsirolimus dose, and Cycle 1 Day 8

Population: Due to early termination of the study by withdrawal of funding by sponsor (Pfizer merged with Wyeth), the peripheral blood samples that were collected for this outcome measure were not analyzed prior to losing funding.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years from completion of treatment

Population: There were only (2) patients evaluable for PFS.

PFS is defined as the duration of time from start of treatment to time of progression.

Outcome measures

Outcome measures
Measure
Phase I (Premetrexed & Temsirolimus)
* Participants enrolled in the Phase I portion Dose Level 1 received: * Pemetrexed 500mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle * Participants enrolled in the Phase I portion Dose Level -1 received: * Pemetrexed 375mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
n=2 Participants
-Participants enrolled in the Phase 2 portion received: * Pemetrexed (375 mg/m2\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
* Phase 2 dose will be the maximum tolerated dose found in the Phase I portion of the study. * Pemetrexed (375 mg/m\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 Only: Progression-free Survival (PFS)
Patient A
523 days
Phase 2 Only: Progression-free Survival (PFS)
Patient B
167 days

SECONDARY outcome

Timeframe: 1 year after start of treatment

Outcome measures

Outcome measures
Measure
Phase I (Premetrexed & Temsirolimus)
* Participants enrolled in the Phase I portion Dose Level 1 received: * Pemetrexed 500mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle * Participants enrolled in the Phase I portion Dose Level -1 received: * Pemetrexed 375mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
n=4 Participants
-Participants enrolled in the Phase 2 portion received: * Pemetrexed (375 mg/m2\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
* Phase 2 dose will be the maximum tolerated dose found in the Phase I portion of the study. * Pemetrexed (375 mg/m\^2) IV on Day 1 of each 21 day cycle * Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 Only: Survival Rate
50 percentage of participants

SECONDARY outcome

Timeframe: Cycle 1 Day 1, one hour post completion of initial temsirolimus dose, and Cycle 1 Day 8

Population: Due to early termination of the study by withdrawal of funding by sponsor (Pfizer merged with Wyeth), the peripheral blood samples that were collected for this outcome measure were not analyzed prior to losing funding.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1, one hour post completion of initial temsirolimus dose, and Cycle 1 Day 8

Population: Due to early termination of the study by withdrawal of funding by sponsor (Pfizer merged with Wyeth), the peripheral blood samples that were collected for this outcome measure were not analyzed prior to losing funding.

Outcome measures

Outcome data not reported

Adverse Events

Phase I (Premetrexed & Temsirolimus)

Serious events: 2 serious events
Other events: 8 other events
Deaths: 0 deaths

Phase 2 (Pemetrexed & Temsirolimus)

Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Phase I (Premetrexed & Temsirolimus)
n=8 participants at risk
* Dose Level 1 * Pemetrexed 500mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle * Dose Level -1 * Pemetrexed 375mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
n=4 participants at risk
Pemetrexed (375 mg/m\^2) IV on Day 1 of each 21 day cycle Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Investigations
Neutrophils (ANC)
12.5%
1/8
0.00%
0/4
Investigations
Leukocytes (WBC)
25.0%
2/8
0.00%
0/4
Investigations
Platelets
12.5%
1/8
0.00%
0/4
Cardiac disorders
Chest pain
12.5%
1/8
0.00%
0/4
Respiratory, thoracic and mediastinal disorders
Dyspnea
12.5%
1/8
0.00%
0/4
Vascular disorders
Pulmonary embolism
25.0%
2/8
25.0%
1/4
General disorders
Disease progression - death
12.5%
1/8
25.0%
1/4
Respiratory, thoracic and mediastinal disorders
Respiratory failure
0.00%
0/8
25.0%
1/4
Infections and infestations
Infection - pneumonia
0.00%
0/8
25.0%
1/4
Infections and infestations
Septic shock
0.00%
0/8
25.0%
1/4
Metabolism and nutrition disorders
Hypocalcemia
12.5%
1/8
0.00%
0/4
Metabolism and nutrition disorders
Hypoalbuminemia
12.5%
1/8
0.00%
0/4
Respiratory, thoracic and mediastinal disorders
Aspiration pneumonitis
0.00%
0/8
25.0%
1/4

Other adverse events

Other adverse events
Measure
Phase I (Premetrexed & Temsirolimus)
n=8 participants at risk
* Dose Level 1 * Pemetrexed 500mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle * Dose Level -1 * Pemetrexed 375mg/m\^2 IV on Day 1 of each 21 day cycle * Temsirolimus 15 mg IV on Days 1,8 and 15 of each 21 day cycle
Phase 2 (Pemetrexed & Temsirolimus)
n=4 participants at risk
Pemetrexed (375 mg/m\^2) IV on Day 1 of each 21 day cycle Temsirolimus (15 mg) IV on Days 1,8 and 15 of each 21 day cycle
Investigations
ALT
37.5%
3/8
50.0%
2/4
Investigations
AST
62.5%
5/8
0.00%
0/4
Metabolism and nutrition disorders
Albumin - low
37.5%
3/8
100.0%
4/4
Investigations
Alkaline phosphatase
37.5%
3/8
0.00%
0/4
Metabolism and nutrition disorders
Anorexia
50.0%
4/8
50.0%
2/4
Investigations
Bilirubin
12.5%
1/8
0.00%
0/4
Skin and subcutaneous tissue disorders
Blood blister
12.5%
1/8
0.00%
0/4
Metabolism and nutrition disorders
Calcium - low
37.5%
3/8
25.0%
1/4
Cardiac disorders
Chest pain
12.5%
1/8
0.00%
0/4
Investigations
Chloesterol - high
0.00%
0/8
50.0%
2/4
Nervous system disorders
Confusion
12.5%
1/8
0.00%
0/4
Gastrointestinal disorders
Constipation
0.00%
0/8
50.0%
2/4
Respiratory, thoracic and mediastinal disorders
Cough
0.00%
0/8
25.0%
1/4
Investigations
Creatinine
25.0%
2/8
25.0%
1/4
Gastrointestinal disorders
Diarrhea
12.5%
1/8
25.0%
1/4
Nervous system disorders
Dizziness
0.00%
0/8
50.0%
2/4
Gastrointestinal disorders
Dysgeusia
0.00%
0/8
25.0%
1/4
Gastrointestinal disorders
Dyspepsia
12.5%
1/8
25.0%
1/4
Respiratory, thoracic and mediastinal disorders
Dyspnea
12.5%
1/8
25.0%
1/4
General disorders
Edema
25.0%
2/8
75.0%
3/4
Respiratory, thoracic and mediastinal disorders
Epistaxis
12.5%
1/8
25.0%
1/4
General disorders
Fatigue
37.5%
3/8
75.0%
3/4
General disorders
Fever
0.00%
0/8
50.0%
2/4
Metabolism and nutrition disorders
Glucose - high
62.5%
5/8
50.0%
2/4
Investigations
Hand pain
12.5%
1/8
0.00%
0/4
Nervous system disorders
Headache
25.0%
2/8
25.0%
1/4
Blood and lymphatic system disorders
Hemoglobin
87.5%
7/8
100.0%
4/4
Vascular disorders
Hot flashes
12.5%
1/8
0.00%
0/4
Vascular disorders
Hypotension
12.5%
1/8
0.00%
0/4
Respiratory, thoracic and mediastinal disorders
Hypoxia
12.5%
1/8
0.00%
0/4
Investigations
INR
12.5%
1/8
0.00%
0/4
General disorders
Infusion reaction
0.00%
0/8
25.0%
1/4
Psychiatric disorders
Insomnia
25.0%
2/8
75.0%
3/4
Investigations
Leukocytes (WBC)
75.0%
6/8
75.0%
3/4
Investigations
Lymphopenia
100.0%
8/8
100.0%
4/4
Metabolism and nutrition disorders
Magnesium - low
12.5%
1/8
0.00%
0/4
Psychiatric disorders
Mood alteration - anxiety
0.00%
0/8
25.0%
1/4
Psychiatric disorders
Mood alteration - depression
12.5%
1/8
50.0%
2/4
Musculoskeletal and connective tissue disorders
Myalgia
0.00%
0/8
25.0%
1/4
Gastrointestinal disorders
Nausea
50.0%
4/8
75.0%
3/4
Investigations
Neutrophils (ANC)
37.5%
3/8
75.0%
3/4
General disorders
Pain NOS
12.5%
1/8
0.00%
0/4
Cardiac disorders
Palpitations
0.00%
0/8
25.0%
1/4
Metabolism and nutrition disorders
Phosphorus - low
25.0%
2/8
25.0%
1/4
Investigations
Platelets
62.5%
5/8
100.0%
4/4
Metabolism and nutrition disorders
Potassium - high
25.0%
2/8
25.0%
1/4
Renal and urinary disorders
Proteinuria
12.5%
1/8
0.00%
0/4
Skin and subcutaneous tissue disorders
Rash
37.5%
3/8
50.0%
2/4
Respiratory, thoracic and mediastinal disorders
Respiratory failure
12.5%
1/8
0.00%
0/4
Nervous system disorders
Sensory neuropathy
0.00%
0/8
25.0%
1/4
Skin and subcutaneous tissue disorders
Skin breakdown/decubitous ulcer
12.5%
1/8
0.00%
0/4
Metabolism and nutrition disorders
Sodium - low
25.0%
2/8
25.0%
1/4
Gastrointestinal disorders
Stomatitis
0.00%
0/8
50.0%
2/4
General disorders
Sweating
0.00%
0/8
25.0%
1/4
Investigations
Throat pain
12.5%
1/8
0.00%
0/4
Investigations
Triglycerides - high
12.5%
1/8
25.0%
1/4
Infections and infestations
Upper respiratory infection
37.5%
3/8
0.00%
0/4
Infections and infestations
Viral flare (herpes)
0.00%
0/8
25.0%
1/4
Gastrointestinal disorders
Vomiting
25.0%
2/8
25.0%
1/4
Eye disorders
Watery eyes
12.5%
1/8
25.0%
1/4
Investigations
Weight loss
25.0%
2/8
25.0%
1/4

Additional Information

Maria Baggstrom, M.D.

Washington University School of Medicine

Phone: 314-362-5737

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place