deltatrials
Active Not Recruiting PHASE1/PHASE2 INTERVENTIONAL 2-arm NCT01989585

Testing the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma

Phase I/II Study of Dabrafenib, Trametinib, and Navitoclax in BRAF Mutant Melanoma (Phase I and II) and Other Solid Tumors (Phase I Only)

Sponsor: National Cancer Institute (NCI)

Conditions Clinical Stage III Cutaneous Melanoma AJCC v8 Clinical Stage IV Cutaneous Melanoma AJCC v8 Malignant Solid Neoplasm Metastatic Melanoma Unresectable Melanoma
Interventions Biopsy Procedure Biospecimen Collection Computed Tomography Dabrafenib Echocardiography Test Laboratory Biomarker Analysis Magnetic Resonance Imaging Multigated Acquisition Scan Navitoclax Pharmacological Study Trametinib
Updated 81 times since 2017 Last updated: Mar 12, 2026 Started: Mar 24, 2014 Primary completion: Dec 31, 2027 Completion: Dec 31, 2027
This information is for research purposes only and is not medical advice. Consult a healthcare provider before making any medical decision.

This PHASE1/PHASE2 trial investigates Clinical Stage III Cutaneous Melanoma AJCC v8 and Clinical Stage IV Cutaneous Melanoma AJCC v8 and is currently ongoing. National Cancer Institute (NCI) leads this study, which shows 81 recorded versions since 2014 — indicating substantial longitudinal coverage. As an oncology study, it adds to the longitudinal record of treatment development for this indication.

Study Description(click to expand)

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD), toxicity, and safety profile of navitoclax when given in combination with dabrafenib and trametinib in patients with BRAF-mutant solid tumors. (Phase I) II. To estimate the complete response (CR) rate in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, and navitoclax as compared to the historical control dabrafenib and trametinib combination (DT). (Phase II) III. To compare the maximal tumor regression in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax. (Phase II) SECONDARY OBJECTIVES: I. To describe pharmacodynamics effects of treatment with dabrafenib, trametinib, and navitoclax on both serial tumor biopsies and serial blood draws in a small subset of patients treated with BRAF-mutant melanoma. (Phase I) II. To describe the pharmacokinetics of treatment with dabrafenib, trametinib, and navitoclax. (Phase I) III. To compare the progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, versus dabrafenib, trametinib, and navitoclax. (Phase II) IV. To compare the degree of apoptosis induced in on-treatment biopsies of patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax. (Phase II) V. To explore other pharmacodynamic effects...

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD), toxicity, and safety profile of navitoclax when given in combination with dabrafenib and trametinib in patients with BRAF-mutant solid tumors. (Phase I) II. To estimate the complete response (CR) rate in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, and navitoclax as compared to the historical control dabrafenib and trametinib combination (DT). (Phase II) III. To compare the maximal tumor regression in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax. (Phase II)

SECONDARY OBJECTIVES:

I. To describe pharmacodynamics effects of treatment with dabrafenib, trametinib, and navitoclax on both serial tumor biopsies and serial blood draws in a small subset of patients treated with BRAF-mutant melanoma. (Phase I) II. To describe the pharmacokinetics of treatment with dabrafenib, trametinib, and navitoclax. (Phase I) III. To compare the progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, versus dabrafenib, trametinib, and navitoclax. (Phase II) IV. To compare the degree of apoptosis induced in on-treatment biopsies of patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax. (Phase II) V. To explore other pharmacodynamic effects in on-treatment biopsies of patients with BRAF-mutant melanoma treated with either dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax including cell proliferation (Ki-67), proteomics (reverse-phase protein microarrays \[RPPA\]), and B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (BCL-2) family gene expression analysis. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of dabrafenib, trametinib, and navitoclax followed by a randomized phase II study.

PHASE I: Patients receive navitoclax orally (PO) once daily (QD) on days -7 to -1 of cycle 1 only. Patients also receive dabrafenib PO twice daily (BID), trametinib PO QD, and navitoclax PO QD days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo electrocardiography (ECHO) or multigated acquisition scan (MUGA), magnetic resonance imaging (MRI) or computed tomography (CT), also undergo biopsy, and collection of blood samples throughout the trial.

PHASE II: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA, MRI or CT, biopsy, and collection of blood samples throughout the trial.

ARM II: Patients receive navitoclax PO QD days -7 to -1 of cycle 1 only. Patients also receive dabrafenib PO BID, trametinib PO QD, and navitoclax PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA, MRI or CT, biopsy, and collection of blood samples throughout the trial.

After the completion of study treatment, patients are followed up for clinical evaluation at 28 days and every 3 months thereafter until disease progression or death, whichever comes first. For survival follow up, patients are followed every 12 months for 3 years.

Status Flow

~Jan 2017 – ~Feb 2017 · 31 days · monthly snapshot~Feb 2017 – ~Jun 2017 · 4 months · monthly snapshot~Jun 2017 – ~Sep 2017 · 3 months · monthly snapshot~Sep 2017 – ~Dec 2017 · 3 months · monthly snapshot~Dec 2017 – ~Feb 2018 · 2 months · monthly snapshot~Feb 2018 – ~Mar 2018 · 28 days · monthly snapshot~Mar 2018 – ~Jun 2018 · 3 months · monthly snapshot~Jun 2018 – ~Aug 2018 · 2 months · monthly snapshot~Aug 2018 – ~Sep 2018 · 31 days · monthly snapshot~Sep 2018 – ~Oct 2018 · 30 days · monthly snapshot~Oct 2018 – ~Nov 2018 · 31 days · monthly snapshot~Nov 2018 – ~Dec 2018 · 30 days · monthly snapshot~Dec 2018 – ~Jan 2019 · 31 days · monthly snapshot~Jan 2019 – ~Mar 2019 · 59 days · monthly snapshot~Mar 2019 – ~Apr 2019 · 31 days · monthly snapshot~Apr 2019 – ~May 2019 · 30 days · monthly snapshot~May 2019 – ~Jun 2019 · 31 days · monthly snapshot~Jun 2019 – ~Jul 2019 · 30 days · monthly snapshot~Jul 2019 – ~Aug 2019 · 31 days · monthly snapshot~Aug 2019 – ~Sep 2019 · 31 days · monthly snapshot~Sep 2019 – ~Oct 2019 · 30 days · monthly snapshot~Oct 2019 – ~Nov 2019 · 31 days · monthly snapshot~Nov 2019 – ~Dec 2019 · 30 days · monthly snapshot~Dec 2019 – ~Jan 2020 · 31 days · monthly snapshot~Jan 2020 – ~Feb 2020 · 31 days · monthly snapshot~Feb 2020 – ~Mar 2020 · 29 days · monthly snapshot~Mar 2020 – ~Apr 2020 · 31 days · monthly snapshot~Apr 2020 – ~May 2020 · 30 days · monthly snapshot~May 2020 – ~Jun 2020 · 31 days · monthly snapshot~Jun 2020 – ~Jul 2020 · 30 days · monthly snapshot~Jul 2020 – ~Aug 2020 · 31 days · monthly snapshot~Aug 2020 – ~Sep 2020 · 31 days · monthly snapshot~Sep 2020 – ~Oct 2020 · 30 days · monthly snapshot~Oct 2020 – ~Nov 2020 · 31 days · monthly snapshot~Nov 2020 – ~Dec 2020 · 30 days · monthly snapshot~Dec 2020 – ~Jan 2021 · 31 days · monthly snapshot~Jan 2021 – ~Feb 2021 · 31 days · monthly snapshot~Feb 2021 – ~Mar 2021 · 28 days · monthly snapshot~Mar 2021 – ~May 2021 · 2 months · monthly snapshot~May 2021 – ~Jun 2021 · 31 days · monthly snapshot~Jun 2021 – ~Sep 2021 · 3 months · monthly snapshot~Sep 2021 – ~Oct 2021 · 30 days · monthly snapshot~Oct 2021 – ~Nov 2021 · 31 days · monthly snapshot~Nov 2021 – ~Dec 2021 · 30 days · monthly snapshot~Dec 2021 – ~Jan 2022 · 31 days · monthly snapshot~Jan 2022 – ~Feb 2022 · 31 days · monthly snapshot~Feb 2022 – ~Mar 2022 · 28 days · monthly snapshot~Mar 2022 – ~Apr 2022 · 31 days · monthly snapshot~Apr 2022 – ~May 2022 · 30 days · monthly snapshot~May 2022 – ~Jun 2022 · 31 days · monthly snapshot~Jun 2022 – ~Jul 2022 · 30 days · monthly snapshot~Jul 2022 – ~Sep 2022 · 2 months · monthly snapshot~Sep 2022 – ~Dec 2022 · 3 months · monthly snapshot~Dec 2022 – ~Feb 2023 · 2 months · monthly snapshot~Feb 2023 – ~May 2023 · 3 months · monthly snapshot~May 2023 – ~Jun 2023 · 31 days · monthly snapshot~Jun 2023 – ~Oct 2023 · 4 months · monthly snapshot~Oct 2023 – ~Dec 2023 · 2 months · monthly snapshot~Dec 2023 – ~Jan 2024 · 31 days · monthly snapshot~Jan 2024 – ~Feb 2024 · 31 days · monthly snapshot~Feb 2024 – ~Apr 2024 · 2 months · monthly snapshot~Apr 2024 – ~May 2024 · 30 days · monthly snapshot~May 2024 – ~Jun 2024 · 31 days · monthly snapshot~Jun 2024 – ~Jul 2024 · 30 days · monthly snapshot~Jul 2024 – ~Aug 2024 · 31 days · monthly snapshot~Aug 2024 – ~Sep 2024 · 31 days · monthly snapshot~Sep 2024 – ~Nov 2024 · 2 months · monthly snapshot~Nov 2024 – ~Dec 2024 · 30 days · monthly snapshot~Dec 2024 – ~Jan 2025 · 31 days · monthly snapshot~Jan 2025 – ~Apr 2025 · 3 months · monthly snapshot~Apr 2025 – ~May 2025 · 30 days · monthly snapshot~May 2025 – ~Jun 2025 · 31 days · monthly snapshot~Jun 2025 – ~Sep 2025 · 3 months · monthly snapshot~Sep 2025 – ~Oct 2025 · 30 days · monthly snapshot~Oct 2025 – ~Dec 2025 · 2 months · monthly snapshot~Dec 2025 – ~Feb 2026 · 2 months · monthly snapshot~Jan 2026 – present · 3 months · monthly snapshot~Feb 2026 – present · 2 months · monthly snapshot~Feb 2026 – ~Mar 2026 · 28 days · monthly snapshot~Mar 2026 – present · 37 days · monthly snapshot~Mar 2026 – present · 37 days · monthly snapshot

Change History

81 versions recorded

  1. Mar 2026 — Present [monthly]

    Active Not Recruiting PHASE1/PHASE2

  2. Mar 2026 — Present [monthly]

    Active Not Recruiting PHASE1/PHASE2

  3. Feb 2026 — Present [monthly]

    Active Not Recruiting PHASE1/PHASE2

  4. Feb 2026 — Mar 2026 [monthly]

    Active Not Recruiting PHASE1/PHASE2

  5. Jan 2026 — Present [monthly]

    Active Not Recruiting PHASE1/PHASE2

▶ Show 76 earlier versions

  1. Dec 2025 — Feb 2026 [monthly]

    Active Not Recruiting PHASE1/PHASE2

  2. Oct 2025 — Dec 2025 [monthly]

    Active Not Recruiting PHASE1/PHASE2

  3. Sep 2025 — Oct 2025 [monthly]

    Active Not Recruiting PHASE1/PHASE2

  4. Jun 2025 — Sep 2025 [monthly]

    Active Not Recruiting PHASE1/PHASE2

  5. May 2025 — Jun 2025 [monthly]

    Active Not Recruiting PHASE1/PHASE2

  6. Apr 2025 — May 2025 [monthly]

    Active Not Recruiting PHASE1/PHASE2

  7. Jan 2025 — Apr 2025 [monthly]

    Active Not Recruiting PHASE1/PHASE2

  8. Dec 2024 — Jan 2025 [monthly]

    Active Not Recruiting PHASE1/PHASE2

  9. Nov 2024 — Dec 2024 [monthly]

    Active Not Recruiting PHASE1/PHASE2

  10. Sep 2024 — Nov 2024 [monthly]

    Active Not Recruiting PHASE1/PHASE2

  11. Aug 2024 — Sep 2024 [monthly]

    Active Not Recruiting PHASE1/PHASE2

  12. Jul 2024 — Aug 2024 [monthly]

    Active Not Recruiting PHASE1/PHASE2

    Phase: PHASE1_PHASE2 → PHASE1/PHASE2

  13. Jun 2024 — Jul 2024 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  14. May 2024 — Jun 2024 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  15. Apr 2024 — May 2024 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  16. Feb 2024 — Apr 2024 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  17. Jan 2024 — Feb 2024 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  18. Dec 2023 — Jan 2024 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  19. Oct 2023 — Dec 2023 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  20. Jun 2023 — Oct 2023 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  21. May 2023 — Jun 2023 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  22. Feb 2023 — May 2023 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  23. Dec 2022 — Feb 2023 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  24. Sep 2022 — Dec 2022 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  25. Jul 2022 — Sep 2022 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  26. Jun 2022 — Jul 2022 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  27. May 2022 — Jun 2022 [monthly]

    Active Not Recruiting PHASE1_PHASE2

  28. Apr 2022 — May 2022 [monthly]

    Active Not Recruiting PHASE1_PHASE2

    Status: Recruiting → Active Not Recruiting

  29. Mar 2022 — Apr 2022 [monthly]

    Recruiting PHASE1_PHASE2

  30. Feb 2022 — Mar 2022 [monthly]

    Recruiting PHASE1_PHASE2

  31. Jan 2022 — Feb 2022 [monthly]

    Recruiting PHASE1_PHASE2

  32. Dec 2021 — Jan 2022 [monthly]

    Recruiting PHASE1_PHASE2

  33. Nov 2021 — Dec 2021 [monthly]

    Recruiting PHASE1_PHASE2

  34. Oct 2021 — Nov 2021 [monthly]

    Recruiting PHASE1_PHASE2

  35. Sep 2021 — Oct 2021 [monthly]

    Recruiting PHASE1_PHASE2

  36. Jun 2021 — Sep 2021 [monthly]

    Recruiting PHASE1_PHASE2

  37. May 2021 — Jun 2021 [monthly]

    Recruiting PHASE1_PHASE2

  38. Mar 2021 — May 2021 [monthly]

    Recruiting PHASE1_PHASE2

  39. Feb 2021 — Mar 2021 [monthly]

    Recruiting PHASE1_PHASE2

  40. Jan 2021 — Feb 2021 [monthly]

    Recruiting PHASE1_PHASE2

  41. Dec 2020 — Jan 2021 [monthly]

    Recruiting PHASE1_PHASE2

  42. Nov 2020 — Dec 2020 [monthly]

    Recruiting PHASE1_PHASE2

  43. Oct 2020 — Nov 2020 [monthly]

    Recruiting PHASE1_PHASE2

  44. Sep 2020 — Oct 2020 [monthly]

    Recruiting PHASE1_PHASE2

  45. Aug 2020 — Sep 2020 [monthly]

    Recruiting PHASE1_PHASE2

  46. Jul 2020 — Aug 2020 [monthly]

    Recruiting PHASE1_PHASE2

  47. Jun 2020 — Jul 2020 [monthly]

    Recruiting PHASE1_PHASE2

  48. May 2020 — Jun 2020 [monthly]

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  49. Apr 2020 — May 2020 [monthly]

    Recruiting PHASE1_PHASE2

  50. Mar 2020 — Apr 2020 [monthly]

    Recruiting PHASE1_PHASE2

  51. Feb 2020 — Mar 2020 [monthly]

    Recruiting PHASE1_PHASE2

  52. Jan 2020 — Feb 2020 [monthly]

    Recruiting PHASE1_PHASE2

  53. Dec 2019 — Jan 2020 [monthly]

    Recruiting PHASE1_PHASE2

  54. Nov 2019 — Dec 2019 [monthly]

    Recruiting PHASE1_PHASE2

  55. Oct 2019 — Nov 2019 [monthly]

    Recruiting PHASE1_PHASE2

  56. Sep 2019 — Oct 2019 [monthly]

    Recruiting PHASE1_PHASE2

  57. Aug 2019 — Sep 2019 [monthly]

    Recruiting PHASE1_PHASE2

  58. Jul 2019 — Aug 2019 [monthly]

    Recruiting PHASE1_PHASE2

  59. Jun 2019 — Jul 2019 [monthly]

    Recruiting PHASE1_PHASE2

  60. May 2019 — Jun 2019 [monthly]

    Recruiting PHASE1_PHASE2

  61. Apr 2019 — May 2019 [monthly]

    Recruiting PHASE1_PHASE2

  62. Mar 2019 — Apr 2019 [monthly]

    Recruiting PHASE1_PHASE2

  63. Jan 2019 — Mar 2019 [monthly]

    Recruiting PHASE1_PHASE2

  64. Dec 2018 — Jan 2019 [monthly]

    Recruiting PHASE1_PHASE2

  65. Nov 2018 — Dec 2018 [monthly]

    Recruiting PHASE1_PHASE2

  66. Oct 2018 — Nov 2018 [monthly]

    Recruiting PHASE1_PHASE2

  67. Sep 2018 — Oct 2018 [monthly]

    Recruiting PHASE1_PHASE2

  68. Aug 2018 — Sep 2018 [monthly]

    Recruiting PHASE1_PHASE2

  69. Jun 2018 — Aug 2018 [monthly]

    Recruiting PHASE1_PHASE2

  70. Mar 2018 — Jun 2018 [monthly]

    Recruiting PHASE1_PHASE2

  71. Feb 2018 — Mar 2018 [monthly]

    Recruiting PHASE1_PHASE2

  72. Dec 2017 — Feb 2018 [monthly]

    Recruiting PHASE1_PHASE2

  73. Sep 2017 — Dec 2017 [monthly]

    Recruiting PHASE1_PHASE2

  74. Jun 2017 — Sep 2017 [monthly]

    Recruiting PHASE1_PHASE2

  75. Feb 2017 — Jun 2017 [monthly]

    Recruiting PHASE1_PHASE2

  76. Jan 2017 — Feb 2017 [monthly]

    Recruiting PHASE1_PHASE2

    First recorded

Mar 2014

Trial started

Per CT.gov start date — pre-dates our first snapshot

Eligibility Summary

No eligibility information available.

Contact Information

Sponsor contact:
  • National Cancer Institute (NCI)
Data source: National Cancer Institute (NCI)

For direct contact, visit the study record on ClinicalTrials.gov .

Study Locations

Aurora, United States , Aventura, United States , Boston, United States , Chapel Hill, United States , Chicago, United States , City of Saint Peters, United States , Columbus, United States , Coral Gables, United States , Creve Coeur, United States , Deerfield Beach, United States and 29 more locations