Summary

Eligibility
for people ages 18-99 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Hope Rugo
Headshot of Hope Rugo
Hope Rugo

Description

Summary

A Phase Ib/III Randomised Study of Capivasertib plus Palbociclib and Fulvestrant versus Placebo plus Palbociclib and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer (CAPItello-292)

Official Title

A Phase Ib/III Randomised Study of Capivasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer

Details

This Phase Ib/III study (CAPItello-292) aims to evaluate the efficacy, safety and the degree of added benefit of capivasertib combined with palbociclib and fulvestrant in participants with endocrine-resistant locally advanced (inoperable) or metastatic HR+/HER2- breast cancer. Although the dosing regimens of capivasertib + fulvestrant and of palbociclib + fulvestrant are established, the dose and schedule for the triplet combination (capivasertib + palbociclib + fulvestrant) needs to be confirmed. Therefore, the initial dose finding Phase Ib part of the study will confirm the recommended Phase III doses (RP3D) and schedule of administration of capivasertib and palbociclib for the triplet combination including fulvestrant which will then be used in the Phase III part of this study.

Keywords

Locally Advanced (Inoperable) or Metastatic Breast Cancer, Breast Neoplasms, Fulvestrant, Palbociclib, Capivasertib, Capivasertib Plus Palbociclib and Fulvestrant

Eligibility

You can join if…

Open to people ages 18-99

for both phases:

  1. Adult females (pre- and/or post-menopausal), and adult males.
  2. Histologically confirmed HR+/ HER2- breast cancer determined from the most recent tumour sample (primary or metastatic) per the American Society of Clinical Oncology and College of American Pathologists guideline. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor.
  3. Eligible for palbociclib and fulvestrant therapy as per investigator assessment. Previous tolerance to specific CDK4/6 inhibitors and dose levels required.
  4. Adequate organ and bone marrow functions.
  5. Consent to provide a mandatory FFPE tumour sample.

Inclusion criteria only for phase III:

  1. Previous treatment with an ET (tamoxifen or an AI) as a single agent or in combination, with:
  2. radiological evidence of breast cancer recurrence or progression while on, or within 12 months of, completing a (neo)adjuvant ET regimen OR
  3. radiological evidence of progression while receiving the ET for locally advanced or metastatic breast cancer (this does not need to be the most recent therapy)
  4. Received up to a maximum of 1 lines of prior chemotherapy in the advanced setting.

You CAN'T join if...

for both phases:

  1. History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention and of low potential risk for recurrence.
  2. Radiotherapy with a wide field of radiation within 4 weeks prior to study treatment initiation and/or radiotherapy with a limited field of radiation for palliation within 2 weeks prior to study treatment initiation. Patients who received prior radiotherapy to ≥25% of bone marrow are not eligible independent of when it was received.
  3. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment.
  4. Persistent toxicities (CTCAE Grade >1) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss) after consultation with the AstraZeneca study physician.
  5. Spinal cord compression, brain metastases or leptomeningeal metastases unless asymptomatic, treated and stable and not requiring steroids within 4 weeks prior to study treatment initiation.
  6. Any of the following cardiac criteria at screening:
  7. . Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 consecutive ECGs
  8. . Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third-degree heart block)
  9. . Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
  10. . Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) grade ≥ 2
  11. . Uncontrolled hypotension
  12. . Cardiac ejection fraction outside institutional range of normal or < 50% (whichever is higher)
  13. Any of these clinically significant abnormalities of glucose metabolism at screening:
  14. . diabetes mellitus type I or type II requiring insulin treatment
  15. . HbA1c ≥ 8.0% (63.9 mmol/mol)
  16. Previous allogeneic bone marrow transplant or solid organ transplant.

Key exclusion criteria for the phase III only:

  1. Any prior treatment with SERDs, AKT, PI3K or mTOR inhibitors.
  2. Prior treatment with CDK4/6 inhibitors in the metastatic setting (prior CDK4/6 inhibitors permitted in the adjuvant setting).

Locations

  • Research Site accepting new patients
    San Francisco California 94158 United States
  • Research Site withdrawn
    Los Angeles California 90048 United States

Lead Scientist at UCSF

  • Hope Rugo
    Dr. Hope Rugo is a medical oncologist and hematologist specializing in breast cancer research and treatment. A Clinical Professor of Medicine, Dr. Rugo joined the Breast Care Center in 1999 after a decade of experience at UCSF in malignant hematology and bone marrow transplantation for a variety of diseases, including breast cancer.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
AstraZeneca
ID
NCT04862663
Phase
Phase 3 research study
Study Type
Interventional
Participants
Expecting 700 study participants
Last Updated