Phase 1b Study of Pegylated Liposomal Doxorubicin and Pembrolizumab in Endocrine-resistant Breast Cancer (KEYDOX)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03591276|
Recruitment Status : Recruiting
First Posted : July 19, 2018
Last Update Posted : April 24, 2019
Very few patients with endocrine-resistant, hormone-receptor positive metastatic breast cancer respond to single agent immunotherapy. Responses to chemotherapy are usually of short duration. Combining immunotherapy with chemotherapy that has minimal immunosuppressive effect, it may be possible to achieve higher response rates while keeping the immune-associated pattern of long durations of response.
This will be a single-center phase 1b study to evaluate the tumor response and appropriate dose of a chemo-immunotherapy regime consisting of treatment with pegylated liposomal doxorubicin (PLD) and pembrolizumab-based in endocrine-resistant breast cancer (ERBC) patients.
Up to 15 female patients, ages 18 and above, with pathological diagnosis of breast cancer, estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2-) negative subtype, stage III non-operable, or stage IV disease, who have received at least two lines of hormonal therapy, one of which included aromatase inhibitors will be eligible for enrollment to this single arm study.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Breast Cancer||Drug: Chemotherapy Drugs, Cancer||Phase 1 Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1b Study of Combination Chemo-immunotherapy With Pegylated Liposomal Doxorubicin (Doxil/Caelyx) and Pembrolizumab (Keytruda) in Metastatic Endocrine-resistant Breast Cancer|
|Actual Study Start Date :||April 18, 2019|
|Estimated Primary Completion Date :||March 15, 2020|
|Estimated Study Completion Date :||June 15, 2020|
Experimental: Pembrolizumab and PLD
Cohort S1: IV pembrolizumab 200 mg flat dose with IV PLD 30 mg/m2 every 3 weeks.
Reduced Dose Cohort (R1)*: IV pembrolizumab 200 mg flat dose with IV PLD 24 mg/m2 every 3 weeks.
*Subjects will be recruited into the R1 cohort only if DLT is reported in 2 or more subjects during the first 2 cycles of treatment in the first 6 patients of the S1 cohort.
Drug: Chemotherapy Drugs, Cancer
IV pembrolizumab 200 mg flat dose with IV PLD 30 mg/m2 (chemotherapy drugs) every 3 weeks in eligible breast cancer patients.
Other Name: Immunotherapy Antibodies, Cancer
- To establish a safe dose of PLD when delivered in combination with pembrolizumab [ Time Frame: At the end of Cycle 2 (day 42), each cyle is 21 days ]A dose will be considered safe when the number of Participants With Treatment-Related Adverse Events grades 3 or 4, as assessed by CTCAE v4.0, will be less than 2 per 6-patient cohort. Our hypothesis is that treatment with pembrolizumab will be compatible with the standard recommended dose of PLD,
- To evaluate the Tumor Response Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) after 9 weeks (3 cycles) of treatment in patients with measurable disease. [ Time Frame: At the end of Cycle 3 (day 63), each cycle is 21 days ]Th response rate will be evaluated after 9 weeks (3 cycles) by RECIST. Our hypothesis is that the response rate of the combination will be higher than expected from each agent alone.
- To evaluate the safety and DLT of the PLD and pembrolizumab combination, as indicated by the number of study participants with treatment-related Adverse Events, and the class of Adverse Events as assessed by CTCAE v4.0. [ Time Frame: At the end of Cycle 2 (day 42), each cycle is 21 days ]The safety profile of PLD and pembrolizumab will be evaluated by the number of study participants with treatment-related Adverse Events, and the class of Adverse Events as assessed by CTCAE v4.0. Our hypothesis is that it will remain unchanged when given in combination, as compared to what expected for each drug alone.
- To characterize the PK of PLD when delivered in combination with pembrolizumab, by measuring and comparing the Area under the curve (AUC) for doxorubicin (liposomal) obtained during Cycles 1 and 3. [ Time Frame: During Cycle 1 (between days 1 and 22), and Cycle 3 (between days 42 and 63), each cycle is 21 days ]The PK of PLD will be evaluated by quantitation of doxorubicin (liposomal) in plasma samples and calculation of the AUC. Hypothesis: The PK profile of PLD may be modified by pembrolizumab during the course of therapy due to indirect effects on the mononuclear-phagocyte system (MPS) which plays an important role in PLD clearance. This will translate into a decrease or increase of AUC when the results of the 1st and 3rd cycles are compared.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03591276
|Contact: Alberto A. Gabizon, MD, PhDemail@example.com|
|Contact: Yair Plesser, MScfirstname.lastname@example.org|
|Shaare Zedek Medical Center||Recruiting|
|Jerusalem, Israel, 91031|
|Contact: Alberto Gabizon, MD, PhD 0508685036 email@example.com|
|Contact: Yair Plesser 0505204342 firstname.lastname@example.org|
|Principal Investigator:||Alberto A Gabizon, MD, PhD||Shaare Zedek MC|