Inhibition of Autophagy Synergizes Anti-tumor EffectPhase 1/2NCT05953350
A Phase Ib/II Study Confirmed Inhibition of Autophagy Synergizes Anti-tumor Effect of High Dose CDK4/6i
A Phase 1/2 study testing 600mg bid dose of hydroxychloroquine combined with three predefined dose groups of palbociclib and RP2D dose of 600mg bid of hydroxychloroquine combined with palbociclib was selected for phase II clinical trial. in people with Inhibition of Autophagy Synergizes Anti-tumor Effect, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
Trial summary
In order to explore the safety and antitumor efficacy of different doses of CDK4/6 inhibitor Palbociclib in combination with the autophagy inhibitor hydroxychloroquine (HCQ) , a phase Ib/II study was conducted. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inhibition of Autophagy Synergizes Anti-tumor Effect
- What is being tested?
- 600mg bid dose of hydroxychloroquine combined with three predefined dose groups of palbociclib and RP2D dose of 600mg bid of hydroxychloroquine combined with palbociclib was selected for phase II clinical trial.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteChina
- Study dates
- 7 Nov 2023to 31 Dec 2024
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients diagnosed with advanced solid tumors (including breast cancer, undifferentiated liposarcoma, etc.) confirmed by histology and/or cytology, who have failed CDK4/6 inhibitor treatment or have experienced failure of neoadjuvant or adjuvant CDK4/6 inhibitor therapy for 12 months.
- At least one measurable target lesion according to RECIST 1.1.
- Age 18 years or older, any gender.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Expected survival of at least 3 months.
- Within one week before enrollment, baseline blood tests should be essentially normal (no blood transfusions or hematopoietic growth factor treatment within 14 days): absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; hemoglobin ≥ 9 g/dL; platelet count (PLT) ≥ 75 × 10^9/L.
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- Within one week before enrollment, baseline liver and kidney function tests should be essentially normal (normal values determined by each study center's laboratory): total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); serum glutamic-pyruvic transaminase (SGPT/ALT) ≤ 3 × ULN (≤ 5 × ULN for patients with liver metastases or liver cancer); serum glutamic-oxaloacetic transaminase (SGOT/AST) ≤ 3 × ULN (≤ 5 × ULN for patients with liver metastases); serum creatinine ≤ 1.5 × ULN or creatinine clearance (Ccr) ≥ 50 ml/min.
- Fertile patients (both males and females) must agree to use a reliable contraceptive method concurrently with their partners during the trial and for at least 3 months after the last dose of medication (hormonal or barrier methods, or abstinence). Pre-menopausal female patients must have a negative pregnancy test in blood or urine before enrollment.
- Pre-menopausal women should provide blood and urine samples to confirm a negative pregnancy status and commit to using contraception during the study period and for 6 months after the study. Male participants are required to commit to using contraception with their partners or female partners during the study period and for 6 months after the study.
Who cannot join
- Patients who have undergone major visceral surgery (excluding needle biopsies) or significant trauma within 4 weeks prior to the first administration of the study drug.
- Prior treatment with radiotherapy and two or more CDK4/6 inhibitors for advanced or metastatic disease.
- Failure to recover from adverse reactions of previous anti-tumor therapy to CTCAE 5.0 grade ≤ 1 (except for acceptable toxicities without safety risks, such as hair loss, and manageable immune-related adverse reactions). Additionally, symptomatic peripheral neuropathy of CTCAE 5.0 grade ≥ 2 resulting from the previous treatment regimen.
- Clinical symptoms of central nervous system metastases or leptomeningeal metastases, or other evidence indicating uncontrolled central nervous system metastases or leptomeningeal metastases deemed unsuitable for enrollment by the investigator.
- Pregnancy (positive pregnancy test) or lactation.
- Active infection requiring systemic antimicrobial therapy that is not under control at present (except for asymptomatic urinary tract infections). History of immune deficiency, including positive HIV antibody testing. History of active hepatitis B (except for controlled cases with antiviral therapy) and positive hepatitis C antibody.
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- History of severe cardiovascular or cerebrovascular diseases, including but not limited to clinically significant cardiac rhythm or conduction abnormalities requiring clinical intervention, ventricular arrhythmias, second- or third-degree atrioventricular block; average QTcF > 470 ms based on three consecutive 12-lead electrocardiograms at rest; acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular events within 6 months before the first dose; uncontrolled hypertension.
- Patients with psychiatric disorders or poor compliance.
- Patients unsuitable for hydroxychloroquine use due to the presence of retinal vascular disease.
- Other systemic medical history or conditions deemed inappropriate for participation in the trial by the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Chang Gong, Phd contact
China1 site, 1 recruiting
- Recruiting
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Guangzhou, Guangdong, 510120
Gong Chang, doctor, 02034070499, changgong282@163.com
About this study
Official title: A Phase Ib/II Study Confirmed Inhibition of Autophagy Synergizes Anti-tumor Effect of High Dose CDK4/6i with Manageable Safety in HR+HER2-breast Cancer Patients
In order to explore the safety and antitumor efficacy of different doses of CDK4/6 inhibitor Palbociclib in combination with the autophagy inhibitor hydroxychloroquine (HCQ) , a phase Ib/II study was conducted.
This study will adopt a 3+3 design and include three predefined dose groups of palbociclib: 100mg QD, 150mg QD, and 200mg QD. Initially, 600mg bid dose of hydroxychloroquine group will be administered in combination. The trial will use the first cycle (28 days) as the observation period for tolerability, observing and evaluating the occurrence of DLTs after medication and determining the maximum tolerated dose/maximum administered dose (MTD/MAD) and recommended phase 2 dose (RP2D) of the combination therapy.
This study improves the efficacy of CDK4/6 inhibitors in the treatment of solid tumors by reversing DTP status through the use of HCQ.
- Being tested
- 600mg bid dose of hydroxychloroquine combined with three predefined dose groups of palbociclib, RP2D dose of 600mg bid of hydroxychloroquine combined with palbociclib was selected for phase II clinical trial.
- Keywords
- inhibition of autophagy, CDK4/6i, hydroxychloroquine, HR+HER2-breast cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
600mg bid dose of hydroxychloroquine combined with three predefined dose groups of palbociclibDrug
hydroxychloroquine group of 600mg bid combined with three predefined dose groups of palbociclib: 100mg QD, 150mg QD, and 200mg QD, separately.
RP2D dose of 600mg bid of hydroxychloroquine combined with palbociclib was selected for phase II clinical trial.Drug
After the exploration of 600mg bid dose of hydroxychloroquine combined with palbociclib, and the maximal tolerated dose (MTD) was determined, then RP2D dose of 600mg bid dose of hydroxychloroquine combined with palbociclib was selected for phase II clinical trial.
| Study group | Role | What they receive |
|---|---|---|
| Phase Ib clinical trial | Experimental | 600mg bid dose of hydroxychloroquine group combined with three predefined dose groups of palbociclib: 100mg QD, 150mg QD, and 200mg QD, separately. Receives: Drug: 600mg bid dose of hydroxychloroquine combined with three predefined dose groups of palbociclib |
| Phase II clinical trial | Experimental | After MTD was determined, RP2D dose was selected for phase II clinical trial. Receives: Drug: RP2D dose of 600mg bid of hydroxychloroquine combined with palbociclib was selected for phase II clinical trial. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety dose of the combination of hydroxychloroquine and CDK4/6 inhibitors in patients
The study aims to evaluate the safety dose of the combination of hydroxychloroquine and CDK4/6 inhibitors in patients with solid tumors. The safety dose was according to "3+3" dose escalation principle.
In this study, Dose-limiting toxicity (DLT) was defined as drug-related adverse reactions (according to the NCI CTC 5.0 grading criteria) after treatment: ≥ Grade II liver and kidney injury, grade III other non-hematological toxicity, and grade IV hematological toxicity.
Measured: 12 months
the recommended phase II dose
The study aims to evaluate the recommended phase II dose of the combination of hydroxychloroquine and CDK4/6 inhibitors in patients with solid tumors.
Measured: 12 months
Secondary outcomes (2)
Objective response rate（ORR）
This study investigates the preliminary efficacy of the combination of hydroxychloroquine and CDK4/6 inhibitors in the treatment of solid tumors.
Measured: 12 months
Progression-free survival (PFS)
This study investigates the preliminary efficacy of the combination of hydroxychloroquine and CDK4/6 inhibitors in the treatment of solid tumors.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2023
- Study start7 Nov 2023
- Primary completion7 May 2024
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Inhibition of Autophagy Synergizes Anti-tumor EffectStudies of the same condition, open and under way.
- More trials run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chang Gong, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05953350
- Sponsor's protocol ID
- SKSKY-2023-488-01
- Status last verified
- Nov 2024
- First submitted
- 12 Jun 2023
- Last updated
- 3 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gong C, Lin Q, Qin T, Zeng Y, Xu F, Yang Y, Yin D, Duan Z, Chen CL, Wing-Cheong Chow L, Liu Q, Hamai A, Mehrpour M, Lin Q, Li J, Song E. Targeting autophagy plus high-dose CDK4/6 inhibitors in advanced HR+HER2- breast cancer: A phase 1b/2 trial. Med. 2025 May 9;6(5):100559. doi: 10.1016/j.medj.2024.11.012. Epub 2024 Dec 27.
PubMed 39731909
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study Confirmed Inhibition of Autophagy Synergizes Anti-tumor Effect of High Dose CDK4/6i with Manageable Safety in HR+HER2-breast Cancer Patients
- ClinicalTrials.gov ID
- NCT05953350
- Acronym / sponsor ID
- SKSKY-2023-488-01
- Keywords
- inhibition of autophagy, CDK4/6i, hydroxychloroquine, HR+HER2-breast cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- 7 Nov 2023 (actual)
- Primary completion
- 7 May 2024 (actual)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 20 Jul 2023 (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.
In order to explore the safety and antitumor efficacy of different doses of CDK4/6 inhibitor Palbociclib in combination with the autophagy inhibitor hydroxychloroquine (HCQ) , a phase Ib/II study was conducted.
This study will adopt a 3+3 design and include three predefined dose groups of palbociclib: 100mg QD, 150mg QD, and 200mg QD. Initially, 600mg bid dose of hydroxychloroquine group will be administered in combination. The trial will use the first cycle (28 days) as the observation period for tolerability, observing and evaluating the occurrence of DLTs after medication and determining the maximum tolerated dose/maximum administered dose (MTD/MAD) and recommended phase 2 dose (RP2D) of the combination therapy.
This study improves the efficacy of CDK4/6 inhibitors in the treatment of solid tumors by reversing DTP status through the use of HCQ.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase Ib clinical trial | Experimental | Drug: 600mg bid dose of hydroxychloroquine combined with three predefined dose groups of palbociclib600mg bid dose of hydroxychloroquine group combined with three predefined dose groups of palbociclib: 100mg QD, 150mg QD, and 200mg QD, separately. |
| Phase II clinical trial | Experimental | Drug: RP2D dose of 600mg bid of hydroxychloroquine combined with palbociclib was selected for phase II clinical trial.After MTD was determined, RP2D dose was selected for phase II clinical trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients diagnosed with advanced solid tumors (including breast cancer, undifferentiated liposarcoma, etc.) confirmed by histology and/or cytology, who have failed CDK4/6 inhibitor treatment or have experienced failure of neoadjuvant or adjuvant CDK4/6 inhibitor therapy for 12 months.
- At least one measurable target lesion according to RECIST 1.1.
- Age 18 years or older, any gender.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Expected survival of at least 3 months.
Key exclusion criteria (10 listed)
- Patients who have undergone major visceral surgery (excluding needle biopsies) or significant trauma within 4 weeks prior to the first administration of the study drug.
- Prior treatment with radiotherapy and two or more CDK4/6 inhibitors for advanced or metastatic disease.
- Failure to recover from adverse reactions of previous anti-tumor therapy to CTCAE 5.0 grade ≤ 1 (except for acceptable toxicities without safety risks, such as hair loss, and manageable immune-related adverse reactions). Additionally, symptomatic peripheral neuropathy of CTCAE 5.0 grade ≥ 2 resulting from the previous treatment regimen.
- Clinical symptoms of central nervous system metastases or leptomeningeal metastases, or other evidence indicating uncontrolled central nervous system metastases or leptomeningeal metastases deemed unsuitable for enrollment by the investigator.
- Pregnancy (positive pregnancy test) or lactation.
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 |
|---|---|---|
| 600mg bid dose of hydroxychloroquine combined with three predefined dose groups of palbociclibhydroxychloroquine group of 600mg bid combined with three predefined dose groups of palbociclib: 100mg QD, 150mg QD, and 200mg QD, separately. | Drug | Phase Ib clinical trial |
| RP2D dose of 600mg bid of hydroxychloroquine combined with palbociclib was selected for phase II clinical trial.After the exploration of 600mg bid dose of hydroxychloroquine combined with palbociclib, and the maximal tolerated dose (MTD) was determined, then RP2D dose of 600mg bid dose of hydroxychloroquine combined with palbociclib was selected for phase II clinical trial. | Drug | Phase II clinical trial |
Primary outcome
The safety dose of the combination of hydroxychloroquine and CDK4/6 inhibitors in patients
Time frame: 12 months
The study aims to evaluate the safety dose of the combination of hydroxychloroquine and CDK4/6 inhibitors in patients with solid tumors. The safety dose was according to "3+3" dose escalation principle. In this study, Dose-limiting toxicity (DLT) was defined as drug-related adverse reactions (according to the NCI CTC 5.0 grading criteria) after treatment: ≥ Grade II liver and kidney injury, grade III other non-hematological toxicity, and grade IV hematological toxicity.
the recommended phase II dose
Time frame: 12 months
The study aims to evaluate the recommended phase II dose of the combination of hydroxychloroquine and CDK4/6 inhibitors in patients with solid tumors.
2 secondary outcomes
Objective response rate（ORR）
Time frame: 12 months
Progression-free survival (PFS)
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2024.
- Derived from this study: PubMed 39731909Gong C, Lin Q, Qin T, Zeng Y, Xu F, Yang Y, Yin D, Duan Z, Chen CL, Wing-Cheong Chow L, Liu Q, Hamai A, Mehrpour M, Lin Q, Li J, Song E. Targeting autophagy plus high-dose CDK4/6 inhibitors in advanced HR+HER2- breast cancer: A phase 1b/2 trial. Med. 2025 May 9;6(5):100559. doi: 10.1016/j.medj.2024.11.012. Epub 2024 Dec 27.
- Individual participant dataSharing planned: No
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.
Chang Gong, Phd contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 600mg bid dose of hydroxychloroquine combined with three predefined dose groups of palbociclib and RP2D dose of 600mg bid of hydroxychloroquine combined with palbociclib was selected for phase II clinical trial. in people with Inhibition of Autophagy Synergizes Anti-tumor Effect, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
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 9 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 3 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tao Qin, Phd (+8613570396232, qint6@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The safety dose of the combination of hydroxychloroquine and CDK4/6 inhibitors in patients (time frame: 12 months). The study lists 2 primary outcomes in all. 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 NCT05953350, which also lists 1 linked publication.
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 3 Dec 2024.