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Safety and Clinical Pharmacology of GDC-0068 in Combination With Docetaxel, Fluoropyrimidine Plus Oxaliplatin, Paclitaxel, or Enzalutamide in Participants With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01362374
Recruitment Status : Completed
First Posted : May 30, 2011
Last Update Posted : January 12, 2022
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Description
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Brief Summary:

This is an open-label, multicenter, Phase Ib, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of oral ipatasertib (GDC-0068) administered in combination with either docetaxel (Arm A), or oxaliplatin, leucovorin, 5-fluorouracil (5-FU) (mFOLFOX6 chemotherapy) (Arm B), or paclitaxel (Arm C), in participants with advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerable. Arm D will assess the safety, tolerability, and pharmacokinetics of ipatasertib administered in combination with enzalutamide in participants with metastatic castration-resistant prostate cancer (CRPC). There will be two stages within each arm of this study: a dose-escalation stage (Stage 1) and a cohort-expansion stage (Stage 2). In Stage 1, approximately 3 to 6 cohorts in Arms A and B and 1 to 2 cohorts in Arms C and D will be evaluated to determine the maximum tolerated dose (MTD) of ipatasertib in a given combination. Additional participants will be enrolled in Stage 2 (cohort expansion), to further characterize the safety and tolerability of ipatasertib in these combinations and to confirm a potential recommended Phase II dose of ipatasertib for each regimen.

NOTE: Arms A, B, and C are closed.


Condition or disease Intervention/treatment Phase
Neoplasms Drug: 5-FU Drug: Docetaxel Drug: Enzalutamide Drug: Ipatasertib Drug: Leucovorin Drug: Oxaliplatin Drug: Paclitaxel Phase 1

Study Design
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Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 122 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib, Open-label, Dose-escalation Study of the Safety and Pharmacology of Ipatasertib (GDC-0068) in Combination With Docetaxel, Fluoropyrimidine Plus Oxaliplatin, Paclitaxel, or Enzalutamide in Patients With Advanced Solid Tumors
Actual Study Start Date : July 11, 2011
Actual Primary Completion Date : October 16, 2020
Actual Study Completion Date : October 16, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A (Doc + Ipat 100mg)
Participants received ipatasertib at a dose of 100 milligrams (mg) once daily for 14 consecutive days (beginning on Day 2) in combination with docetaxel on Day 1, in 21-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first.
 Drug: Docetaxel
Docetaxel will be administered at dose level of 75 mg/m^2 as IV infusion over 1 hr on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Drug: Ipatasertib
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.
Experimental: Arm A (Doc + Ipat 200mg)
Participants received ipatasertib at a dose of 200mg once daily for 14 consecutive days (beginning on Day 2) in combination with docetaxel on Day 1, in 21-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first.
 Drug: Docetaxel
Docetaxel will be administered at dose level of 75 mg/m^2 as IV infusion over 1 hr on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Drug: Ipatasertib
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.
Experimental: Arm A (Doc + Ipat 400mg)
Participants received ipatasertib at a dose of 400mg once daily for 14 consecutive days (beginning on Day 2) in combination with docetaxel on Day 1, in 21-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first.
 Drug: Docetaxel
Docetaxel will be administered at dose level of 75 mg/m^2 as IV infusion over 1 hr on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Drug: Ipatasertib
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.
Experimental: Arm A (Doc + Ipat 600mg)
Participants received ipatasertib at a dose of 600mg once daily for 14 consecutive days (beginning on Day 2) in combination with docetaxel on Day 1, in 21-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first.
 Drug: Docetaxel
Docetaxel will be administered at dose level of 75 mg/m^2 as IV infusion over 1 hr on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Drug: Ipatasertib
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.
Experimental: Arm B (mFOLFOX + Ipat 100mg)
Participants received ipatasertib at a dose of 100mg once daily for 7 consecutive days (beginning on Day 1) in combination with mFOLFOX6 chemotherapy (comprising of oxaliplatin, leucovorin, and 5-FU) on Day 1, in 14-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first.
 Drug: 5-FU
5-FU at a dose level of 400 mg/m^2 as intravenous (IV) injection followed by a dose of 2400 mg/m^2 as IV infusion over 46 hrs will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
Other Name: Adrucil

Drug: Ipatasertib
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.

Drug: Leucovorin
Leucovorin at a dose level of 400 mg/m^2 as IV infusion over 2 hrs will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
Other Name: Wellcovorin

Drug: Oxaliplatin
Oxaliplatin at a dose level of 85 mg/m^2 as IV infusion over 2 hours will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
Other Name: Eloxatin
Experimental: Arm B (mFOLFOX + Ipat 200mg)
Participants received ipatasertib at a dose of 200mg once daily for 7 consecutive days (beginning on Day 1) in combination with mFOLFOX6 chemotherapy (comprising of oxaliplatin, leucovorin, and 5-FU) on Day 1, in 14-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first.
 Drug: 5-FU
5-FU at a dose level of 400 mg/m^2 as intravenous (IV) injection followed by a dose of 2400 mg/m^2 as IV infusion over 46 hrs will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
Other Name: Adrucil

Drug: Ipatasertib
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.

Drug: Leucovorin
Leucovorin at a dose level of 400 mg/m^2 as IV infusion over 2 hrs will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
Other Name: Wellcovorin

Drug: Oxaliplatin
Oxaliplatin at a dose level of 85 mg/m^2 as IV infusion over 2 hours will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
Other Name: Eloxatin
Experimental: Arm B (mFOLFOX + Ipat 400mg)
Participants received ipatasertib at a dose of 400mg once daily for 7 consecutive days (beginning on Day 1) in combination with mFOLFOX6 chemotherapy (comprising of oxaliplatin, leucovorin, and 5-FU) on Day 1, in 14-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first.
 Drug: 5-FU
5-FU at a dose level of 400 mg/m^2 as intravenous (IV) injection followed by a dose of 2400 mg/m^2 as IV infusion over 46 hrs will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
Other Name: Adrucil

Drug: Ipatasertib
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.

Drug: Leucovorin
Leucovorin at a dose level of 400 mg/m^2 as IV infusion over 2 hrs will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
Other Name: Wellcovorin

Drug: Oxaliplatin
Oxaliplatin at a dose level of 85 mg/m^2 as IV infusion over 2 hours will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
Other Name: Eloxatin
Experimental: Arm B (mFOLFOX + Ipat 600mg)
Participants received ipatasertib at a dose of 600mg once daily for 7 consecutive days (beginning on Day 1) in combination with mFOLFOX6 chemotherapy (comprising of oxaliplatin, leucovorin, and 5-FU) on Day 1, in 14-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first.
 Drug: 5-FU
5-FU at a dose level of 400 mg/m^2 as intravenous (IV) injection followed by a dose of 2400 mg/m^2 as IV infusion over 46 hrs will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
Other Name: Adrucil

Drug: Ipatasertib
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.

Drug: Leucovorin
Leucovorin at a dose level of 400 mg/m^2 as IV infusion over 2 hrs will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
Other Name: Wellcovorin

Drug: Oxaliplatin
Oxaliplatin at a dose level of 85 mg/m^2 as IV infusion over 2 hours will be administered on Day 1 of each 14-day cycle until disease progression or unacceptable toxicity.
Other Name: Eloxatin
Experimental: Arm C (Pac + Ipat 400mg)
Participants received ipatasertib at a dose of 400mg once daily for 21 consecutive days (beginning on Day 1) in combination with paclitaxel on Days 1, 8, and 15, in 28-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first.
 Drug: Ipatasertib
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.

Drug: Paclitaxel
Paclitaxel at a dose of 90 mg/m^2 as IV infusion over 1 hr will be administered on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.
Other Name: Taxol
Experimental: Arm C (Pac + Ipat 600mg)
Participants received ipatasertib at a dose of 600mg once daily for 21 consecutive days (beginning on Day 1) in combination with paclitaxel on Days 1, 8, and 15, in 28-day continuous cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first.
 Drug: Ipatasertib
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.

Drug: Paclitaxel
Paclitaxel at a dose of 90 mg/m^2 as IV infusion over 1 hr will be administered on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.
Other Name: Taxol
Experimental: Arm D (Enza + Ipat 400mg)
Participants received ipatasertib at a dose of 400mg once daily alone for 8 days, then from Day 9, ipatasertib will be administered in combination with enzalutamide once daily for 27 days (Cycle 1 duration = 35 days). Participants received both ipatasertib and enzalutamide once daily continuously in subsequent 28-days cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Higher (up to 600 mg) or lower dose of ipatasertib may be evaluated in subsequent cycles depending upon safety, tolerability, and pharmacokinetics of the first cycle.
 Drug: Enzalutamide
Enzalutamide will be administered orally at a dose level of 160 mg once daily continuously as per schedule defined in respective arm until disease progression or unacceptable toxicity.

Drug: Ipatasertib
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.
Experimental: Arm D (Enza + Ipat 600mg)
Participants received ipatasertib at a dose of 600mg once daily alone for 8 days, then from Day 9, ipatasertib will be administered in combination with enzalutamide once daily for 27 days (Cycle 1 duration = 35 days). Participants received both ipatasertib and enzalutamide once daily continuously in subsequent 28-days cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Higher (up to 600 mg) or lower dose of ipatasertib may be evaluated in subsequent cycles depending upon safety, tolerability, and pharmacokinetics of the first cycle.
 Drug: Enzalutamide
Enzalutamide will be administered orally at a dose level of 160 mg once daily continuously as per schedule defined in respective arm until disease progression or unacceptable toxicity.

Drug: Ipatasertib
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.
Experimental: Arm D (Enza + Ipat 400-600mg)
Participants received ipatasertib at a dose of 400-600mg once daily alone for 8 days, then from Day 9, ipatasertib will be administered in combination with enzalutamide once daily for 27 days (Cycle 1 duration = 35 days). Participants received both ipatasertib and enzalutamide once daily continuously in subsequent 28-days cycles, until disease progression, unacceptable toxicity, or use of another anti-cancer therapy, whichever occurred first. Higher (up to 600 mg) or lower dose of ipatasertib may be evaluated in subsequent cycles depending upon safety, tolerability, and pharmacokinetics of the first cycle.
 Drug: Enzalutamide
Enzalutamide will be administered orally at a dose level of 160 mg once daily continuously as per schedule defined in respective arm until disease progression or unacceptable toxicity.

Drug: Ipatasertib
Ipatasertib will be administered orally (in escalating doses during Stage 1 followed by at a dose decided during Stage 1) as per schedule defined in the respective arms.


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Arm A: Days 2-21 of Cycle 1 (cycle length=21 days); Arm B: Days 1-14 of Cycles 1 and 2 (cycle length=14 days); Arm C: Days 1-28 of Cycle 1 (cycle length=28 days); Arm D: Days 1-35 of Cycle 1 (cycle length=28 days except for Cycle 1=35 days) ]
  2. Maximum Tolerated Dose (MTD) of Ipatasertib [ Time Frame: Arm A: Days 2-21 of Cycle 1 (cycle length=21 days); Arm B: Days 1-14 of Cycles 1 and 2 (cycle length=14 days); Arm C: Days 1-28 of Cycle 1 (cycle length=28 days); Arm D: Days 1-35 of Cycle 1 (cycle length=28 days except for Cycle 1=35 days) ]
  3. Recommended Phase II Dose (RP2D) of Ipatasertib [ Time Frame: Arm A: Days 2-21 of Cycle 1 (cycle length=21 days); Arm B: Days 1-14 of Cycles 1 and 2 (cycle length=14 days); Arm C: Days 1-28 of Cycle 1 (cycle length=28 days); Arm D: Days 1-35 of Cycle 1 (cycle length=28 days except for Cycle 1=35 days) ]
  4. Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline up until 30 days following the last administration of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to a maximum of 9.25 years). ]

Secondary Outcome Measures :
  1. Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Docetaxel (Arm A) [ Time Frame: Immediately prior to docetaxel infusion, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours (hrs) after start of docetaxel infusion on Day 1 Cycles 1 and 2 (1 cycle=21 days) ]
  2. Plasma Terminal Half-Life (t1/2) of Docetaxel (Arm A) [ Time Frame: Immediately prior to docetaxel infusion, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours (hrs) after start of docetaxel infusion on Day 1 Cycles 1 and 2 (1 cycle=21 days) ]
  3. Plasma Clearance (CL) of Docetaxel (Arm A) [ Time Frame: Immediately prior to docetaxel infusion, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours (hrs) after start of docetaxel infusion on Day 1 Cycles 1 and 2 (1 cycle=21 days) ]
  4. Volume of Distribution (Vz) of Docetaxel (Arm A) [ Time Frame: Immediately prior to docetaxel infusion, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours (hrs) after start of docetaxel infusion on Day 1 Cycles 1 and 2 (1 cycle=21 days) ]
  5. Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Total Platinum (Arm B) [ Time Frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days) ]
  6. Plasma Terminal Half-Life (t1/2) of Total Platinum (Arm B) [ Time Frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days) ]
  7. Plasma CL of Total Platinum (Arm B) [ Time Frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days) ]
  8. Vz of Total Platinum (Arm B) [ Time Frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days) ]
  9. Maximum Observed Plasma Concentration (Cmax) of Total Platinum (Arm B) [ Time Frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days) ]
  10. Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Free Platinum (Arm B) [ Time Frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days) ]
  11. Plasma Terminal Half-Life (t1/2) of Free Platinum (Arm B) [ Time Frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days) ]
  12. Plasma CL of Free Platinum (Arm B) [ Time Frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days) ]
  13. Vz of Free Platinum (Arm B) [ Time Frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days) ]
  14. Maximum Observed Plasma Concentration (Cmax) of Free Platinum (Arm B) [ Time Frame: 1, 2, 2.25, 2.5, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days) ]
  15. Cmax of 5-FU (Arm B) [ Time Frame: 2, 2.25, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days) ]
  16. Steady-State Concentration (Css) of 5-FU (Arm B) [ Time Frame: 2, 2.25, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days) ]
  17. Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of 5-FU (Arm B) [ Time Frame: 2, 2.25, 3, 4, 6, 24, 48 hrs after ipatasertib Day 1 dose in Cycle 1 (1 cycle=14 days) ]
  18. Cmax of Paclitaxel (Arm C) [ Time Frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days) ]
  19. Cmax of Paclitaxel Metabolite (Arm C) [ Time Frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days) ]
  20. AUC(0-inf) of Paclitaxel (Arm C) [ Time Frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days) ]
  21. AUC(0-inf) of Paclitaxel Metabolite (Arm C) [ Time Frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days) ]
  22. Plasma CL of Paclitaxel (Arm C) [ Time Frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days) ]
  23. Plasma CL of Paclitaxel Metabolite (Arm C) [ Time Frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days) ]
  24. Vz of Paclitaxel (Arm C) [ Time Frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days) ]
  25. Vz of Paclitaxel Metabolite (Arm C) [ Time Frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days) ]
  26. Plasma t1/2 of Paclitaxel (Arm C) [ Time Frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days) ]
  27. Plasma t1/2 of Paclitaxel Metabolite (Arm C) [ Time Frame: 1, 2, 3, 4, 6, 24 hrs after ipatasertib Day 8 dose in Cycle 1 (1 cycle=28 days) ]
  28. AUC(0-24) of Enzalutamide (Arm D) [ Time Frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days) ]
  29. AUC(0-24) of Enzalutamide Metabolite (Arm D) [ Time Frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days) ]
  30. Time to Reach Cmax (Tmax) of Enzalutamide (Arm D) [ Time Frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days) ]
  31. Tmax of Enzalutamide Metabolite (Arm D) [ Time Frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days) ]
  32. Cmax at Steady State (Cmax,ss) of Enzalutamide (Arm D) [ Time Frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days) ]
  33. Cmax,ss of Enzalutamide Metabolite (Arm D) [ Time Frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days) ]
  34. AUC(0-24) of Ipatasertib (Arm D) [ Time Frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days) ]
  35. AUC(0-24) of Ipatasertib Metabolite (G037720) (Arm D) [ Time Frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days) ]
  36. Tmax of Ipatasertib (Arm D) [ Time Frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days) ]
  37. Tmax of Ipatasertib Metabolite (Arm D) [ Time Frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days) ]
  38. Cmax,ss of Ipatasertib (Arm D) [ Time Frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days) ]
  39. Cmax,ss of Ipatasertib Metabolite (Arm D) [ Time Frame: Day 8 Cycle 1,2 and Day 1 Cycle 3: Immediately prior to ipatasertib dose, 1,2,3,4,6,24 hours post dose (Cycle=28 days except for Cycle 1=35 days) ]
  40. Tmax of Ipatasertib (Arm A) [ Time Frame: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS on Day 2 Cycle 1 (1 cycle=21 days) ]
  41. Tmax of Ipatasertib (Arm B) [ Time Frame: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS Day 1 Cycle 1 (1 cycle=14 days) ]
  42. Tmax of Ipatasertib (Arm C) [ Time Frame: PRDS, 1, 2, 3, 4, 6, 24 hrs PSDS Day 8 Cycle 1 (1 cycle=28 days) ]
  43. Tmax of Ipatasertib Metabolite (Arm A) [ Time Frame: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS on Day 2 Cycle 1 (1 cycle=21 days) ]
  44. Tmax of Ipatasertib Metabolite (Arm B) [ Time Frame: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS Day 1 Cycle 1 (1 cycle=14 days) ]
  45. Tmax of Ipatasertib Metabolite (Arm C) [ Time Frame: PRDS, 1, 2, 3, 4, 6, 24 hrs PSDS Day 8 Cycle 1 (cycles=21 days, Cycle 1=35 days) ]
  46. Cmax,ss of Ipatasertib (Arm A) [ Time Frame: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS on Day 2 Cycle 1 (1 cycle=21 days) ]
  47. Cmax,ss of Ipatasertib (Arm B) [ Time Frame: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS Day 1 Cycle 1 (1 cycle=14 days) ]
  48. Cmax,ss of Ipatasertib (Arm C) [ Time Frame: PRDS, 1, 2, 3, 4, 6, 24 hrs PSDS Day 8 Cycle 1 (1 cycle=28 days) ]
  49. Cmax,ss of Ipatasertib Metabolite (Arm A) [ Time Frame: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS on Day 2 Cycle 1 (1 cycle=21 days) ]
  50. Cmax,ss of Ipatasertib Metabolite (Arm B) [ Time Frame: PRDS, 0.5, 1, 2, 3, 4, 6, 24 hrs PSDS Day 1 Cycle 1 (1 cycle=14 days) ]
  51. Cmax,ss of Ipatasertib Metabolite (Arm C) [ Time Frame: PRDS, 1, 2, 3, 4, 6, 24 hrs PSDS Day 8 Cycle 1 (1 cycle=28 days) ]
  52. Number of Participants With Objective Response as Determined by Investigator Review of Tumor Assessments Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 6 years) ]
  53. Duration of Response (DOR) as Determined by Investigator Review of Tumor Assessments Using RECIST v1.1 [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 6 years) ]
  54. Progression-free Survival (PFS) as Determined by Investigator Review of Tumor Assessments Using RECIST v1.1 [ Time Frame: Baseline up to disease progression or death, whichever occurs first (up to approximately 6 years) ]
  55. Radiographic Progression-free Survival (rPFS) as Determined by Investigator (Arm D only) [ Time Frame: Baseline up to radiographic disease progression or death, whichever occurs first (up to approximately 6 years) ]
  56. Time to Treatment Failure (TTF) [ Time Frame: Baseline up to treatment discontinuation for any reason (up to approximately 6 years) ]

Eligibility Criteria
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Information from the National Library of Medicine

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

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening
  • Histologically or cytologically documented advanced or metastatic solid tumors for which established therapy either does not exist or has proven ineffective or intolerable
  • Life expectancy greater than or equal to (>=) 12 weeks
  • Adequate hematologic and end organ function
  • For female participants of childbearing potential and male participants with partners of childbearing potential, agreement (by participant and/or partner) to use highly effective forms of contraception and to continue its use for the duration of the study and for 4 months after last dose of study treatment (for females) and 6 months after last dose of study treatment (for males)

Exclusion Criteria:

  • Prior anti-cancer therapy that fulfills the following criteria: a total of more than three (Arms A and B) or two (Arms C and D) prior cytotoxic chemotherapy regimens, high-dose chemotherapy requiring stem-cell support, and irradiation to >=25 percent (%) of bone marrow-bearing areas
  • Treatment with chemotherapy, hormonal therapy (except hormone replacement therapy, oral contraceptives, or gonadotropin-releasing hormone (GnRH) agonists or antagonists for prostate cancer), immunotherapy, biologic therapy, radiation therapy (except palliative radiation to bony metastases), or herbal therapy as cancer therapy within 4 weeks prior to initiation of ipatasertib. Exceptions are kinase inhibitors approved by local regulatory authorities, which may be used within 2 weeks prior to initiation of ipatasertib, provided that any clinically-relevant drug-related toxicity has completely resolved and prior approval is obtained from the Medical Monitor
  • Palliative radiation to bony metastases within 2 weeks prior to initiation of ipatasertib
  • History of Type 1 or Type 2 diabetes requiring regular medication
  • Grade >= 2 heart failure or history of unstable angina
  • History of clinically significant ventricular arrhythmias or active ventricular arrhythmia requiring medication
  • For Arm D only: History of seizure, unexplained loss of consciousness, transient ischemic attack within 12 months of enrollment, cerebral vascular accident, and any brain metastases
Contacts and Locations
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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): NCT01362374


Locations
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United States, California
California Pacific Med Center
San Francisco, California, United States, 94115
United States, Florida
Florida Cancer Specialists - Sarasota
Sarasota, Florida, United States, 34232
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
University Of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89128
United States, Tennessee
SCRI
Nashville, Tennessee, United States, 37203
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
France
Institut Gustave Roussy; Departement Oncologie Medicale
Villejuif, France, 94805
Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 08035
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010
United Kingdom
The Royal Marsden Hospital
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Genentech, Inc.
Investigators
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Study Director: Daniel Maslyar, M.D. Genentech, Inc.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01362374    
Other Study ID Numbers: PAM4983g
GO27845 ( Other Identifier: Hoffmann-La Roche )
2011-000782-13 ( EudraCT Number )
First Posted: May 30, 2011    Key Record Dates
Last Update Posted: January 12, 2022
Last Verified: January 2022
Additional relevant MeSH terms:
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Leucovorin
Paclitaxel
Docetaxel
Oxaliplatin
Ipatasertib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
 Molecular Mechanisms of Pharmacological Action
Antidotes
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Protein Kinase Inhibitors
Enzyme Inhibitors