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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
29
hydroxychloroquine group of 600mg bid combined with three predefined dose groups of palbociclib: 100mg QD, 150mg QD, and 200mg QD, separately.
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.
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Guangzhou, Guangdong, China
RECRUITINGThe 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.
Time frame: 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.
Time frame: 12 months
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.
Time frame: 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.
Time frame: 12 months
Chang Gong, Phd
CONTACT
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