NCT02384239

A Study of Palbociclib in Combination With Fulvestrant or Tamoxifen as Treatment for Metastatic Breast Cancer

Completed Phase 2 Results posted Last updated 16 March 2022

What this trial tests

Phase 2 trial testing Palbociclib in Metastatic Breast Cancer in 70 participants. Completed in 31 January 2021.

Timeline

19 October 2015

Primary endpoint
31 January 2021

31 January 2021

Quick facts

Lead sponsor	University of California, San Francisco
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	70
Start date	19 October 2015
Primary completion	31 January 2021
Estimated completion	31 January 2021
Sites	9 locations across United States

Drugs / interventions tested

• Palbociclib (Palbociclib) — full drug profile →
• Tamoxifen — full drug profile →
• Fulvestrant (fulvestrant) — full drug profile →

Conditions studied

• Metastatic Breast Cancer — all drugs for Metastatic Breast Cancer →
• Hormone Receptor Positive — all drugs for Hormone Receptor Positive →

Sponsor

University of California, San Francisco

Who can join

18 and older, any sex, with Metastatic Breast Cancer or Hormone Receptor Positive. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Grade 3 or 4 Neutropenia Primary · Up to 24 months

Grade 3/4 neutropenia as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03 in patients with prior exposure to 1-3 lines of chemotherapy for metastatic breast cancer

Group	Value	95% CI
Palbociclib 100mg	19.4
Palbociclib 125mg	20.5

Progression-free Survival (PFS) Secondary · Up to 24 months

PFS defined as the interval from study entry to the first documented evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the longest diameter (SLD) of target lesions, taking as reference the smallest sum SLD recorded since the treatment started and minimum 5 mm increase over the nadir, or the appearance of one or more new lesions. Patients who remain progression-free at the time of analysis will be censored at their last date of follow-up.

Group	Value	95% CI
Palbociclib 100mg	6.53	2.33 – 12.2
Palbociclib 125mg	9.4	3.56 – 19.7

Proportion of Participants With Demonstrated Clinical Benefit Secondary · 24 weeks

Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) or stable disease (SD) at 24 weeks. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.

Group	Value	95% CI
Palbociclib 100mg	0.67
Palbociclib 125mg	0.75

Proportion of Participants With an Objective Response Secondary · 24 weeks

Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) at 24 weeks. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.

Group	Value	95% CI
Palbociclib 100mg	0.1111
Palbociclib 125mg	0.0625

Median Change in Percent Positive Cells From Baseline of Ki-67 Secondary · Up to 24 months

Median change in percent positive cells of Ki-67 from baseline will be reported with IQR

Group	Value	95% CI
Palbociclib 100mg	-8	-22 – 0
Palbociclib 125mg	-6	-19 – -1

Median Change in Percent Positive Cells From Baseline of Total-Rb Secondary · Up to 24 months

Median change in percent positive cells of Total-Rb from baseline will be reported with interquartile range (IQR)

Group	Value	95% CI
Palbociclib 100mg	4	-25 – 30
Palbociclib 125mg	5	-15 – 29

Median Change in Percent Positive Cells From Baseline of pS780-Rb Secondary · Up to 24 months

Median change in percent positive cells of pS780-Rb from baseline will be reported with IQR

Group	Value	95% CI
Palbociclib 100mg	-3	-32 – 4
Palbociclib 125mg	-6	-14 – 12

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 24 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Palbociclib 100mg

Serious: 5/36 (14%)

Deaths: 3/36

Palbociclib 125mg

Serious: 2/34 (6%)

Deaths: 1/34

Serious adverse events (5 terms)

Reaction	System	Palbociclib 100mg	Palbociclib 125mg
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—
Gastrointestinal disorders - Other	Gastrointestinal disorders	—	—
Infections and infestations - Other	Infections and infestations	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Respiratory, thoracic and mediastinal disorders - Other	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (2 terms — click to expand)

Reaction	System	Palbociclib 100mg	Palbociclib 125mg
Neutrophil count decreased	Investigations	—	—
Hypertension	Vascular disorders	—	—

Most-reported serious reactions: Pleural effusion, Gastrointestinal disorders - Other, Infections and infestations - Other, Dehydration, Respiratory, thoracic and mediastinal disorders - Other.

Data from ClinicalTrials.gov NCT02384239 adverse events section.

Sponsor's own description

This phase II trial studies the side effects of palbociclib when given together with fulvestrant or tamoxifen citrate in treating patients with hormone receptor positive breast cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic). Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hormone therapy using fulvestrant or tamoxifen citrate may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving palbociclib together with fulvestrant or tamoxifen citrate may work better in treating hormone receptor positive breast cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cyclin D1, cancer progression, and opportunities in cancer treatment.
   Qie S, Diehl JA. · · 2016 · cited 527× · PMID 27695879 · DOI 10.1007/s00109-016-1475-3
2. Updates on the CDK4/6 Inhibitory Strategy and Combinations in Breast Cancer.
   Sobhani N, D'Angelo A, Pittacolo M, Roviello G, et al · · 2019 · cited 117× · PMID 30959874 · DOI 10.3390/cells8040321
3. Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases.
   Shah N, Mohammad AS, Saralkar P, Sprowls SA, et al · · 2018 · cited 102× · PMID 29604436 · DOI 10.1016/j.phrs.2018.03.021
4. Chemoresistance in breast cancer: PI3K/Akt pathway inhibitors vs the current chemotherapy.
   Kaboli PJ, Imani S, Jomhori M, Ling KH. · · 2021 · cited 51× · PMID 34765318
5. Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy.
   He Y, de Araújo Júnior RF, Cruz LJ, Eich C. · · 2021 · cited 48× · PMID 34683963 · DOI 10.3390/pharmaceutics13101670
6. Latest Overview of the Cyclin-Dependent Kinases 4/6 Inhibitors in Breast Cancer: The Past, the Present and the Future.
   Chen X, Xu D, Li X, Zhang J, et al · · 2019 · cited 37× · PMID 31777590 · DOI 10.7150/jca.33079
7. Progress with palbociclib in breast cancer: latest evidence and clinical considerations.
   Rocca A, Schirone A, Maltoni R, Bravaccini S, et al · · 2017 · cited 37× · PMID 28203301 · DOI 10.1177/1758834016677961
8. Palbociclib for the Treatment of Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.
   Morikawa A, Henry NL. · · 2015 · cited 25× · PMID 26100274 · DOI 10.1158/1078-0432.ccr-15-0390