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Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)

ConditionLocally Advanced (Inoperable) or Metastatic Breast Cancer
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-99
SponsorAstraZeneca

About this trial

A Phase Ib/III Open-label, Randomised Study of Capivasertib plus CDK4/6 Inhibitors and Fulvestrant versus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer (CAPItello-292)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adult females (pre-/peri-/ and post-menopausal), and adult males.

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.

Eligible for fulvestrant therapy and at least one of the following: palbociclib, ribociclib, or abemaciclib, as per local investigator assessment. Previous tolerance to specific CDK4/6 inhibitors and dose levels required.

Adequate organ and bone marrow functions.

Disqualifiers

History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence.

Radiotherapy within 2 weeks prior to study treatment initiation.

Major surgery or significant traumatic injury within 4 weeks of the first dose of study treatment.

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 or peripheral sensory neuropathy) after consultation with the AstraZeneca study physician.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Capivasertib

    Drug

    Phase Ib: Capivasertib 320 mg/ 400 mg administered PO BD 4 days on /3 days off per week for 4 weeks (28 days cycle) Phase III: : Capivasertib, administered PO BD 4 days on / 3 days off per week for 4 weeks (28 days cycle) at the dose confirmed in the phase Ib portion

  • Fulvestrant

    Drug

    Phase Ib and Phase III: 500 mg (2 injections of 250 mg) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter

  • Palbociclib

    Drug

    Phase Ib: 100 mg/ 125 mg. Once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete 28-day cycle Phase III: Administered once daily for 21 days of 28-day cycle, at the dose of 125 mg.

  • Ribociclib

    Drug

    Phase Ib: 200 mg/ 400 mg/ 600 mg. Once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete 28-day cycle Phase III: Administered once daily for 21 days of 28-day cycle, at the dose confirmed in the phase 1b portion.

  • Abemaciclib

    Drug

    Phase Ib: 50 mg/ 100 mg/ 150 mg. Twice daily for 28 consecutive days to comprise a complete 28-day cycle

Treatment groups

895 Participants
are divided into 5 treatment groups
Group A: Capivasertib Plus Palbociclib and FulvestrantExperimental treatment 3 interventions
Group B: Capivasertib Plus Ribociclib and FulvestrantExperimental treatment 1 intervention
Group C: Capivasertib Plus Abemaciclib and FulvestrantExperimental treatment 1 intervention
Group D: Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib)Experimental treatment 1 intervention
Group E: Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib)Active comparator 1 intervention

Trial outcomes

Primary outcomes

1

Phase Ib: 1. The number of participants with dose-limiting toxicity, as defined in the protocol.

Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria.

Time frame
Within the first 28 day cycle.
2

Phase Ib: 2. The number of participants with treatment-related adverse events.

Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events.

Time frame
From baseline up to approximately 36 months.
3

Phase Ib: 3. The number of participants with treatment-related serious adverse events.

Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events.

Time frame
From baseline up to approximately 36 months.
4

Phase III: 1. Progression Free Survival (PFS).

Progression Free Survival (PFS) is defined as time from randomization until progression per RECIST v1.1. as assessed by BICR or death due to any cause in the overall population, the altered population, and the confirmed non-altered population. RECIST related endpoints such as PFS, ORR, DoR, CBR will be collected.

Time frame
Up to approximately 47 months.

Secondary outcomes

1

Phase Ib: 1. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmax.

Maximum observed plasma (peak) drug concentration.

Time frame
Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days).
2

Phase Ib: 2. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-72h.

Partial area under the plasma concentration-time curve from zero to 72 hours post-dose.

Time frame
Cycle 0 (Cycle 0 is 3 days).
3

Phase Ib: 3. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-24h.

Partial area under the plasma concentration-time curve from zero to 24 hours post-dose.

Time frame
Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days).
4

Phase Ib: 4. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmin.

Minimum observed plasma drug concentration.

Time frame
Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 0 is 3 days and Cycle 1 is 28 days).

Other outcomes

Sponsors and contacts

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AstraZeneca

Lead sponsor

Source ClinicalTrials.gov
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