Breast Neoplasm FemalePhase 1PALVENNCT03900884

Palbociclib, Letrozole & Venetoclax in ER and BCL-2 Positive Breast Cancer

A Phase 1 study testing Venetoclax, Palbociclib and Letrozole in people with Breast Neoplasm Female, run by Peter MacCallum Cancer Centre, Australia at 3 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study is investigating the combination of palbociclib, letrozole and venetoclax in ER and BCL-2 positive locally advanced or metastatic breast cancer. It is hypothesised that venetoclax may augment the actions of palbociclib and letrozole in these patient groups. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Breast Neoplasm Female
What is being tested?: Venetoclax, Palbociclib and Letrozole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 17 participants
Where: 3 sitesAustralia
Study dates: 25 Sep 2019to 19 Mar 2026
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Patient has provided written informed consent for the main PALVEN study.
Female patients ≥ 18 years of age at screening.
Postmenopausal, defined as:
Age ≥60 years, or
Age <60 years and undergone bilateral oophorectomy or medically confirmed ovarian failure, or
Age <60 years and have cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have serum levels of oestradiol and FSH within the reference range for postmenopausal females.

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If pre or peri menopausal, patients must be willing to receive ovarian suppression/ablation, commencing ≥28 days prior to first dose of treatment.
Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1. (Appendix 1).
Patient must have histological or cytological confirmation of metastatic carcinoma of the breast (either from the primary or metastatic site) or locally advanced breast cancer not amenable to surgical or local therapy with curative intent, with the following tumour molecular characteristics (as determined from pre-screening testing):
ER positive (defined as ≥10% positive stained carcinoma cells).
BCL-2 positive (defined as ≥50% cells with at least moderate cytoplasmic staining; intensity 2-3 on a 0-3 scale).
HER2 non-amplified (per ASCO/CAP guidelines).
Patients must be willing to provide tissue after two weeks of treatment from a newly obtained core or excisional biopsy of a tumour lesion where feasible. Patients for whom a repeat biopsy cannot be provided (e.g. inaccessible or patient safety concern) may be eligible only upon agreement from the Coordinating Principal Investigator.
Patients have received no more than a total of two prior lines of systemic therapy for metastatic breast cancer. This can include one line of chemotherapy.
Patients must have measurable disease (according to RECIST v1.1) or evaluable disease. Bone-only metastases are allowed.
Patents must have adequate organ and bone marrow function as defined below within 14 days prior to registration:
Haemoglobin ≥ 90 g/L.
Absolute neutrophil count ≥ 1.5 x 109/L.
Platelet count ≥ 100 x 109/L.
ALT and AST ≤ 2.5 x upper limit of normal (ULN), or ≤ 5 x ULN if liver metastases are present.
Total serum bilirubin ≤ 1.5 x ULN. Patient's with Gilbert's syndrome may have a total serum bilirubin > 1.5 x ULN.
Creatinine Clearance ≥ 50 mls/min (Cockcroft-Gault, please see Appendix 2).
Female patients of childbearing potential must have negative urine or serum pregnancy test within 14 days prior to registration.
Life expectancy > 6 months.
Patient is able to swallow whole tablets.
Female patients of childbearing potential must be willing to use at least one of the following methods of contraception for the course of the study through to 30 days after the last dose of study medication:
Total abstinence from sexual intercourse as the preferred lifestyle of the patient (periodic abstinence is not acceptable).
Intrauterine device (IUD) or Mirena.
Double-barrier method (contraceptive sponge, diaphragm or cervical cap with spermicidal jellies or cream and a condom).

Who cannot join

Patients who have previously been exposed to venetoclax (ABT-199) or a CDK4/6 inhibitor (in the adjuvant or metastatic setting).
Patients who are pregnant or lactating.
Patients with evidence of CNS metastases.
Receipt of any anti-cancer therapy received within 21 days of registration including chemotherapy, radiotherapy, endocrine therapy (aromatase inhibitors, Selective Estrogen Receptor Modulator such as tamoxifen, or a Selective Estrogen Receptor Degrader such as fulvestrant) or other investigational therapy. The following therapies ARE permitted:
Bisphosphonate or denosumab therapy for patients with bone metastases.
Ovarian suppression in pre- and peri-menopausal patients.

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Prior radiotherapy to a target lesion site, unless there has been unequivocal progression at that site following radiotherapy.
Patients who are taking warfarin or other oral anticoagulant therapy. The use of alternative anticoagulation therapy such as systemic low-molecular weight heparin will be acceptable.
Patients who have had major surgery within 28 days of first dose of study drug or anticipation of the need for major surgery during the course of study treatment.
Patients that have received any of the following agents within 7 days prior to registration:
Steroid therapy for anti-neoplastic intent.
CYP3A inhibitors e.g. fluconazole, ketoconazole, clarithromycin.
Potent CYP3A inducers e.g. rifampicin, carbamazepine, phenytoin, St. John's Wort.
Drugs that are known to prolong the QT interval (see Appendix 5).
Consumption of one or more of the following within 3 days prior to the first dose of study drugs:
Grapefruit or grapefruit products.
Seville oranges including marmalade containing Seville oranges.
Star fruit (carambola).
Need for current chronic corticosteroid therapy (≥10 mg of prednisone per day or an equivalent dose of other corticosteroids).
Patients with active uncontrolled infection.
Patients with a known history of human immunodeficiency virus (HIV) infection, chronic Hepatitis B or C.
Patients who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible.
Patients with a post or resolved hepatitis B virus (HBV) infection (defined as having a positive HBcAb and negative HbsAg) may be included if HBV DNA is undetectable. These patients must be willing to undergo monthly DNA testing.
Administration of live, attenuated vaccine within 28 days prior to registration or anticipation of need for such a vaccine during the study.
Patients with a history of other malignancies within the past 5 years except for treated skin basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma ≤1.0mm without ulceration, localised thyroid cancer, or cervical carcinoma in situ. Other malignancies considered to be at low risk of recurrence may also be included according to the discretion of the Investigator.
Patients with visceral spread at risk of short-term life-threatening complications.
Patients with a history of medical or psychiatric conditions that may interfere with the patient's participation in the study.
Patients on contraception that is oestrogen or progestin based (Mirena accepted).
Patients who are on Hormone Replacement Therapy.
Patients with a QTc ≥ 480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes
Patients with an uncontrolled electrolyte disorder that can compound the effects of a QTc-prolonging drug (e.g. hypocalcemia, hypokalemia, hypomagnesemia)
History of a malabsorption syndrome or other condition that would interfere with enteral absorption of study drugs.

Trial locations and contacts

3 sites in 1 country.

Australia3 sites

Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Royal Melbourne Hospital
Melbourne, Victoria, 3052
Austin Health
Melbourne, Victoria, 3084

Other trials in Australia

About this study

Official title: A Phase 1b Study of Palbociclib, Letrozole and Venetoclax in ER and BCL-2 Positive Locally Advanced or Metastatic Breast Cancer

This study is investigating the combination of palbociclib, letrozole and venetoclax in ER and BCL-2 positive locally advanced or metastatic breast cancer.

It is hypothesised that venetoclax may augment the actions of palbociclib and letrozole in these patient groups. The primary objective of the study is to determine the maximum tolerated dose of the combination treatment, which can be used in subsequent studies. The study will also investigate disease response and survival.

Participants will receive palbociclib (daily, on days 1-21 of each 28 day cycle), letrozole (daily, on days 1-28 of each 28 day cycle) and venetoclax (daily, on days 1-21 of each 28 day cycle) until the last patient has completed 18 months treatment on the study.

Conditions: Breast Neoplasm Female
Being tested: Venetoclax, Palbociclib, Letrozole

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VenetoclaxDrug
At commencement of study: Venetoclax will commence at 100 mg daily (oral) for days 1-21 of each 28 day cycle. This is a dose finding study so doses will be adjusted between 100 and 800 mg/day depending on dose escalation results and recommendation of the safety committee.
PalbociclibDrug
At commencement of study: Palbociclib will commence at 100 mg daily (oral) for days 1-21 of each 28 day cycle. This is a dose finding study so doses will be adjusted between 75 and 125 mg/day depending on dose escalation results and recommendation of the safety committee.
LetrozoleDrug
Letrozole will be dosed daily at a fixed dose of 2.5 mg/day throughout the study.

Study groups in NCT03900884
Study group	Role	What they receive
Letrozole + Palbociclib + Venetoclax	Experimental	The Letrozole dose is 2.5 mg (D1-28) for all dose levels. Starting dose Level 1: Palbociclib 100 mg (D1-21) and Venetoclax 100 mg (D1-21) daily. Receives: Drug: Venetoclax; Drug: Palbociclib; Drug: Letrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

Determination of the Maximum Tolerated Dose (MTD), dose-limiting toxicities (DLTs) and recommended phase 2 dose of drug combination of palbociclib, letrozole and venetoclax.
To determine the MTD and DLTs of the combination of palbociclib, letrozole and venetoclax in ER positive, BCL-2 positive, HER2 negative metastatic breast cancer or locally advanced breast cancer not amenable to surgical or local therapy with curative intent, and to identify the recommended Phase 2 dose.
Measured: 36 months

Secondary outcomes (5)

Safety profile of the combination of palbociclib, letrozole and venetoclax: CTCAE V 5
Toxicities measured using CTCAE V 5
Measured: maximum 36 months
Response Rate
To describe the best response (according to RECIST v1.1), defined as Complete Response (CR) or Partial Response (PR) or stable disease (SD) at 24 weeks.
Measured: 24 weeks
Overall survival
Overall survival (OS) defined as the time from commencement of the study to date of death from any cause
Measured: 36 months
Clinical benefit rate
To estimate clinical benefit rate (CBR), defined as CR, PR or SD.
Measured: 36 months
Patient reported outcomes
Defined as treatment-related symptoms, patient functioning, and health-related quality of life associated with venetoclax in combination with palbociclib and letrozole. Assessed through patient reported outcomes using a validated quality of life questionnaire - EORTC QLQ C30. The questionnaire is deigned to evaluate change in quality of life over time. Outcomes are rated by the patient on a numerical scale over 28 questions of between 1-4 With 1 being no issue to 4 being a significant issue. There are an additional 2 questions regarding overall quality of life which are rated on a numerical scale 1-7 with 1 being the poorest and 7 being excellent.
Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Sep 201919 Mar 2026

First posted3 Apr 2019
Study start25 Sep 2019
Primary completion19 Mar 2026
Study completion19 Mar 2026

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Breast Neoplasm FemaleStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: This is a Phase 1b, open-label, multicentre dose escalation study of venetoclax in combination with palbociclib and letrozole in patients with ER positive and BCL-2 positive metastatic breast cancer. The study will enrol up to 36 patients with metastatic breast cancer, with the objective of defining the MTD of venetoclax in combination with palbociclib and letrozole. There will be up to a total of 6 dose levels. Three 'step-down' levels will also be included to incorporate the options of reducing the dose of palbociclib if required. The MTD will be the RP2D of palbociclib, letrozole and venetoclax.
Masking: None (open label)
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03900884
Sponsor's protocol ID: 18/028
Acronym: PALVEN
Status last verified: Oct 2026
First submitted: 1 Apr 2019
Last updated: 2 Nov 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Rodriguez Y, Unno K, Truica MI, Chalmers ZR, Yoo YA, Vatapalli R, Sagar V, Yu J, Lysy B, Hussain M, Han H, Abdulkadir SA. A Genome-Wide CRISPR Activation Screen Identifies PRRX2 as a Regulator of Enzalutamide Resistance in Prostate Cancer. Cancer Res. 2022 Jun 6;82(11):2110-2123. doi: 10.1158/0008-5472.CAN-21-3565.
PubMed 35405009
Muttiah C, Whittle JR, Oakman C, Lindeman GJ. PALVEN: phase Ib trial of palbociclib, letrozole and venetoclax in estrogen receptor- and BCL2-positive advanced breast cancer. Future Oncol. 2022 May;18(15):1805-1816. doi: 10.2217/fon-2021-1450. Epub 2022 Feb 21.
PubMed 35187951

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1b Study of Palbociclib, Letrozole and Venetoclax in ER and BCL-2 Positive Locally Advanced or Metastatic Breast Cancer
ClinicalTrials.gov ID: NCT03900884
Acronym / sponsor ID: PALVEN / 18/028
Conditions: Breast Neoplasm Female
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: Peter MacCallum Cancer Centre, AustraliaUniversity, hospital or other
Study start: 25 Sep 2019 (actual)
Primary completion: 19 Mar 2026 (actual)
Study completion: 19 Mar 2026 (actual)
First posted: 3 Apr 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study is investigating the combination of palbociclib, letrozole and venetoclax in ER and BCL-2 positive locally advanced or metastatic breast cancer.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: This is a Phase 1b, open-label, multicentre dose escalation study of venetoclax in combination with palbociclib and letrozole in patients with ER positive and BCL-2 positive metastatic breast cancer. The study will enrol up to 36 patients with metastatic breast cancer, with the objective of defining the MTD of venetoclax in combination with palbociclib and letrozole. There will be up to a total of 6 dose levels. Three 'step-down' levels will also be included to incorporate the options of reducing the dose of palbociclib if required. The MTD will be the RP2D of palbociclib, letrozole and venetoclax.

Arm	Type	Receives
Letrozole + Palbociclib + Venetoclax	Experimental	Drug: Venetoclax, Drug: Palbociclib, Drug: LetrozoleThe Letrozole dose is 2.5 mg (D1-28) for all dose levels. Starting dose Level 1: Palbociclib 100 mg (D1-21) and Venetoclax 100 mg (D1-21) daily.

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (29 listed)

Patient has provided written informed consent for the main PALVEN study.
Female patients ≥ 18 years of age at screening.
Postmenopausal, defined as:
If pre or peri menopausal, patients must be willing to receive ovarian suppression/ablation, commencing ≥28 days prior to first dose of treatment.
Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1. (Appendix 1).

Key exclusion criteria (32 listed)

Patients who have previously been exposed to venetoclax (ABT-199) or a CDK4/6 inhibitor (in the adjuvant or metastatic setting).
Patients who are pregnant or lactating.
Patients with evidence of CNS metastases.
Receipt of any anti-cancer therapy received within 21 days of registration including chemotherapy, radiotherapy, endocrine therapy (aromatase inhibitors, Selective Estrogen Receptor Modulator such as tamoxifen, or a Selective Estrogen Receptor Degrader such as fulvestrant) or other investigational therapy. The following therapies ARE permitted:
Prior radiotherapy to a target lesion site, unless there has been unequivocal progression at that site following radiotherapy.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VenetoclaxAt commencement of study: Venetoclax will commence at 100 mg daily (oral) for days 1-21 of each 28 day cycle. This is a dose finding study so doses will be adjusted between 100 and 800 mg/day depending on dose escalation results and recommendation of the safety committee.	Drug	Letrozole + Palbociclib + Venetoclax
PalbociclibAt commencement of study: Palbociclib will commence at 100 mg daily (oral) for days 1-21 of each 28 day cycle. This is a dose finding study so doses will be adjusted between 75 and 125 mg/day depending on dose escalation results and recommendation of the safety committee.	Drug	Letrozole + Palbociclib + Venetoclax
LetrozoleLetrozole will be dosed daily at a fixed dose of 2.5 mg/day throughout the study.	Drug	Letrozole + Palbociclib + Venetoclax

Primary outcome

Determination of the Maximum Tolerated Dose (MTD), dose-limiting toxicities (DLTs) and recommended phase 2 dose of drug combination of palbociclib, letrozole and venetoclax.
Time frame: 36 months
To determine the MTD and DLTs of the combination of palbociclib, letrozole and venetoclax in ER positive, BCL-2 positive, HER2 negative metastatic breast cancer or locally advanced breast cancer not amenable to surgical or local therapy with curative intent, and to identify the recommended Phase 2 dose.

5 secondary outcomes

Safety profile of the combination of palbociclib, letrozole and venetoclax: CTCAE V 5
Time frame: maximum 36 months
Response Rate
Time frame: 24 weeks
Overall survival
Time frame: 36 months
Clinical benefit rate
Time frame: 36 months
Patient reported outcomes
Time frame: 36 months

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
Derived from this study: PubMed 35405009Rodriguez Y, Unno K, Truica MI, Chalmers ZR, Yoo YA, Vatapalli R, Sagar V, Yu J, Lysy B, Hussain M, Han H, Abdulkadir SA. A Genome-Wide CRISPR Activation Screen Identifies PRRX2 as a Regulator of Enzalutamide Resistance in Prostate Cancer. Cancer Res. 2022 Jun 6;82(11):2110-2123. doi: 10.1158/0008-5472.CAN-21-3565.
Derived from this study: PubMed 35187951Muttiah C, Whittle JR, Oakman C, Lindeman GJ. PALVEN: phase Ib trial of palbociclib, letrozole and venetoclax in estrogen receptor- and BCL2-positive advanced breast cancer. Future Oncol. 2022 May;18(15):1805-1816. doi: 10.2217/fon-2021-1450. Epub 2022 Feb 21.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Geoffrey Lindeman, MBBS FRACP PhD principal investigator

Peter MacCallum Cancer Centre, Australia

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax, Palbociclib and Letrozole in people with Breast Neoplasm Female, run by Peter MacCallum Cancer Centre, Australia at 3 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determination of the Maximum Tolerated Dose (MTD), dose-limiting toxicities (DLTs) and recommended phase 2 dose of drug combination of palbociclib, letrozole and venetoclax. (time frame: 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03900884, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.