Phase 1
N=590
A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer
Non-Small Cell Lung Cancer ALK-positive · Non-Small Cell Lung Cancer c-Met Dependent · Non-Small Cell Lung Cancer ROS Marker Positive · Systemic Anaplastic Large-Cell Lymphoma · Advanced Malignancies Except Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT00585195 ↗Enrolled (actual)
590
Serious AEs
47.9%
Results posted
Oct 2021
Primary outcome: Primary: Dose-Escalation Cohort: Maximum Tolerated Dose (MTD) of Crizotinib — 250; 250; 250; 250 milligram
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- PF-02341066 (Drug); Rifampin (Drug); Itraconazole (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Jul 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Dose-Escalation Cohort: Maximum Tolerated Dose (MTD) of Crizotinib |
250; 250; 250; 250; 250; 250 | — |
| PRIMARY Dose-Escalation Cohort: Recommended Phase 2 Dose (RP2D) of Crizotinib |
250; 250; 250; 250; 250; 250 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Crizotinib on Day -7 |
274.43; 1378.05; 946.93; 1817.35; 2320.00; 3457 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Day -7 |
137.40; 658.64; 338.39; 558.01; 863.00; 1731 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 1 Day 1 |
457.55; 383.98; 763.71; 663.39 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 1 Day 15 |
206.13; 1086.99; 2047.13; 1780.21; 3083.93; 4066.67 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 2 Day 1 |
425.90; 1595.58; 1719.30; 2255.70; 3054.45; 3644.72 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Trough Concentration (Ctrough) of Crizotinib Cycle 1 Day 15 |
7.29; 32.61; 48.18; 126.76; 232.59; 307.83 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Trough Concentration (Ctrough) of Crizotinib on Cycle 2 Day 1 |
12.68; 31.91; 54.04; 157.24; 232.45; 329.50 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Day -7 |
24.19; 67.64; 55.73; 87.02; 130.00; 184.7 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 1 Day 1 |
54.89; 64.14; 114.09; 98.86 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 1 Day 15 |
24.44; 85.66; 149.06; 188.84; 326.51; 420.15 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 2 Day 1 |
47.99; 133.69; 146.26; 238.84; 327.94; 474.68 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Day -7 |
2.00; 4.09; 4.00; 4.00; 2.02; 4.00 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Cycle 1 Day 1 |
2.52; 4.00; 4.00; 4.05 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Cycle 1 Day 15 |
2.00; 2.51; 4.07; 5.01; 4.00; 4.99 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib Cycle 2 Day 1 |
1.02; 3.98; 4.00; 4.00; 4.00; 4.05 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Plasma Decay Half-Life (t1/2) of Crizotinib on Day -7 |
48.20; 46.70; 52.60; 47.35; 45.70; 43.33 | — |
| PRIMARY Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Number of Participants With Treatment Emergent Adverse Events (TEAES) and Serious Adverse Events (SAEs) |
3; 4; 8; 7; 8; 6 | — |
| PRIMARY Dose-Escalation Cohort: Number of Participants With Dose-limiting Toxicities (DLT) |
0; 0; 1; 0; 0; 2 | — |
| PRIMARY Midazolam Interaction Cohort: Maximum Observed Plasma Concentration (Cmax) of Midazolam When Taken Alone or Taken With Crizotinib |
14.98; 19.26; 13.65; 32.62; 12.78; 25.37 | — |
| PRIMARY Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Midazolam When Taken Alone or Taken With Crizotinib |
41.77; 90.78; 37.71; 151.45; 32.10; 112.78 | — |
| PRIMARY RP2D Cohort: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Crizotinib When Taken With Food |
1212.86 | — |
| PRIMARY RP2D Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib When Taken With Food |
106.24 | — |
| PRIMARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib Alone and When Taken With Rifampin |
3110; 509.6 | — |
| PRIMARY Rifampin Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib Alone and When Taken With Rifampin |
326.4; 71.53 | — |
| PRIMARY Rifampin Cohort: Ctrough of Crizotinib Alone and When Taken With Rifampin |
251.7; 26.67 | — |
| PRIMARY Itraconazole Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib When Taken Alone and When Taken With Itraconazole |
4102; 6665 | — |
| PRIMARY Itraconazole Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib When Taken Alone and When Taken With Itraconazole |
259.9; 353.2 | — |
| PRIMARY Itraconazole Cohort: Trough Plasma Concentration (Ctrough) of Crizotinib When Taken Alone and When Taken With Itraconazole |
136.0; 214.0 | — |
| PRIMARY Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Objective Response (OR) |
71.7; 32.3; 31.6; 19.0; 61.2; 8.3 | — |
| PRIMARY Recommended Phase 2 Dose (RP2D) Cohort: Duration of Response (DOR) |
14.5; 6.8; 5.2; 26.2 | — |
| PRIMARY Recommended Phase 2 Dose (RP2D) Cohort: Time to Response (TTR) |
7.9; 7.6; 8.0; 7.7 | — |
| PRIMARY Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Disease Control at Week 8 |
86.8; 71.8; 79.3; 47.6 | — |
| PRIMARY Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Disease Control at Week 16 |
79.2; 51.8; 67.2; 42.9 | — |
| PRIMARY Recommended Phase 2 Dose (RP2D) Cohort: Progression Free Survival (PFS) |
19.3; 7.6; 4.0; 10.0 | — |
| PRIMARY Recommended Phase 2 Dose (RP2D) Cohort: Probability of Being Event Free at Month 6 |
76.9; 57.5; 39.0; 71.9 | — |
| PRIMARY Recommended Phase 2 Dose (RP2D) Cohort: Overall Survival (OS) |
51.4; 20.0; 10.1; NA | — |
| PRIMARY Probability of Participant Survival at Month 6 |
90.5; 86.7; 67.8; 90.0 | — |
| PRIMARY Probability of Participant Survival at Month 12 |
78.8; 66.0; 37.1; 80.5 | — |
| PRIMARY Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 1 Day 15 |
0.46; 0.53; 1.19; 0.58; 0.77; 0.96 | — |
| PRIMARY Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 2 Day 1 |
0.47; 0.72; 0.89; 0.42; 0.69; 1.31 | — |
| PRIMARY Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 4 Day 1 |
0.48; 0.66; 0.84; 0.75; 0.88; 1.63 | — |
| PRIMARY Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 6 Day 1 |
0.49; 0.75; 0.69; 0.78; 1.07; 1.71 | — |
| PRIMARY Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 9 Day 1 |
0.38; 0.56; 1.19; 0.72; 0.83; 1.23 | — |
| PRIMARY Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 12 Day 1 |
0.38; 0.66; 1.06; 0.88; 1.02; 1.39 | — |
| PRIMARY Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 15 Day 1 |
0.49; 1.03; 1.32; 0.90; 0.81; 1.71 | — |
| PRIMARY Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 18 Day 1 |
0.32; 0.55; 1.64; 0.69; 0.89; 1.10 | — |
| PRIMARY Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 21 Day 1 |
0.23; 0.48; 1.46; 0.53; 0.77; 1.23 | — |
| PRIMARY Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 24 Day 1 |
0.39; 0.70; 1.13; 0.69; 0.53; 2.35 | — |
| PRIMARY Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 27 Day 1 |
0.46; 0.97; 1.48; 0.70; 0.66; 1.86 | — |
| PRIMARY Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 30 Day 1 |
0.16; 0.38; 1.14; 0.85; 0.80; 1.25 | — |
| PRIMARY Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at End of Treatment |
0.40; 0.66; 1.48; 0.52; 0.85; 0.62 | — |
Summary
PF-02341066 may work in cancer by blocking the cell growth, migration and invasion of tumor cells. PF-02341066 is a new class of drugs called c-Met/Hepatocyte growth factor receptor tyrosine kinase inhibitors. This compound is also an inhibitor of the anaplastic lymphoma kinase (called ALK) tyrosine kinase and ROS receptor tyrosine kinases. This research study is the first time PF-02341066 will be given to people. PF-02341066 is taken by mouth daily.
Eligibility Criteria
Inclusion Criteria
- Advanced malignancies (except leukemias), histologically proven at diagnosis; Histologically confirmed advanced malignancies that are known to be sensitive to PF-03241066 inhibition, e.g. ALK, c-MET and ROS
- Solid tumors must have measurable disease (Recommended Phase 2 Dose Cohort patients with non-measurable disease may enter on a case-by-case basis); not required for DDI sub-studies.
- Adequate blood cell counts, kidney function, liver function and Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 (for the Recommended Phase 2 Cohort, a ECOG score of 2 may be allowed on a case-by-case basis)
Exclusion Criteria
- Major surgery, radiation therapy or anti-cancer therapy within 2 to 4 weeks of starting study treatment, depending on the patient cohort
- Prior stem cell transplant except of patients with neuroblastoma, lymphoma or myeloma
- Active or unstable cardiac disease or heart attack within 3 months of starting study treatment
Data sourced from ClinicalTrials.gov (NCT00585195). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.