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NCT Number: NCT01362374

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

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.

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Key information

Conditions

Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Institut Gustave Roussy; Departement Oncologie Medicale, Villejuif, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

5-FU

Drug

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 names: Adrucil

docetaxel

Drug

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.

Enzalutamide

Drug

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.

Ipatasertib

Drug

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.

Leucovorin

Drug

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 names: Wellcovorin

Oxaliplatin

Drug

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 names: Eloxatin

paclitaxel

Drug

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 names: Taxol

Primary outcomes

  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 outcomes

  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)

Sponsors and collaborators

Lead sponsor

Genentech, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2011
Primary completion
2020
Study completion
2020
First posted
May 30, 2011
Registry last updated
Jan 12, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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