Maximum Tolerated Dose (MTD) of Liposomal Doxorubicin in Combination With Seliciclib for Patients With Metastatic Triple Negative Breast Cancer (TNBC)

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01333423
First received: April 8, 2011
Last updated: June 22, 2012
Last verified: June 2012
  Purpose

The goal of this clinical research study is to find the highest tolerable dose of seliciclib that can be given in combination with liposomal doxorubicin to patients with metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: Liposomal Doxorubicin
Drug: Seliciclib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I With Dose Expansion to Determine the Maximum Tolerated Dose of Liposomal Doxorubicin in Combination With Seliciclib for the Treatment of Patients With Metastatic Triple Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Participants with a Dose Limiting Toxicity(DLT) [ Time Frame: Cycle 1 of therapy (28 days) ] [ Designated as safety issue: Yes ]
    Dose-limiting toxicity (DLT) defined as NCI Common Toxicity Criteria (version 4.0): Grade 3 or 4 thrombocytopenia lasting > 2 weeks; Grade 3 or 4 neutropenia lasting >2 weeks; Febrile neutropenia; Grade 3 or 4 non-hematologic toxicity that lasts > 72 hours despite appropriate medical management (excluding grade 3 fatigue); or Delay in administration of cycle 2 of therapy for >2 weeks due to myelosuppression. DLT must be considered treatment related and occur during cycle 1 of therapy.


Secondary Outcome Measures:
  • Number of Participants with Clinical Response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Disease response assessed using standard imaging techniques every two cycles. Response measured and defined using modified RECIST criterias of CR, PR or SD at 6 months where Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in sum of longest diameter of target lesions, taking as reference baseline sum longest diameter; and Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD), taking as reference smallest sum of longest diameter since treatment started.


Enrollment: 0
Study Start Date: September 2012
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doxil + Seliciclib
Doxil (Liposomal doxorubicin) 40 mg/m2 intravenous (IV) over 2 -3 hours on Day 4 and Seliciclib starting dose 200 mg orally twice a day on Days 1 - 3 of 28 day cycle
Drug: Liposomal Doxorubicin
40 mg by vein administered over 2 -3 hours on Day 4 of a 28 day cycle.
Other Names:
  • Doxil
  • Doxorubicin Hydrochloride (Liposomal)
Drug: Seliciclib
Starting dose 200 mg by mouth twice daily on Days 1 - 3 of a 28 day cycle.

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  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Both male and female patients with invasive cancer that is confirmed ER/PR/HER2 negative carcinoma of the breast with locally advanced or stage IV disease that is not amenable to curative therapy. For purposes of this study, triple negative disease will be tumors that have ER/PR <10% and HER2 </=1+ by IHC or HER2 FISH non-amplified (ratio <2.0).
  2. Patients must have an ECOG performance status of 0, 1 or 2
  3. Age >/= 18 years
  4. Women must not be pregnant or lactating because of the teratogenic potential of these drugs. All females of childbearing potential (i.e. A female not free from menses > 1 year or not surgically sterilized) must have a blood test or urine study within 2 weeks prior to start of therapy to rule out pregnancy.
  5. Women of childbearing potential (i.e. A female not free from menses > 1 year or not surgically sterilized) and are strongly advised to use an accepted and effective non-hormonal method of contraception.
  6. Must have at least one site of objective measurable or evaluable disease. Baseline measurements and evaluations must be obtained within 4 weeks of start of therapy.
  7. Patients must be disease free of prior malignancy for >/= 5 years with the exception of curatively treated squamous cell carcinomas of the skin or carcinoma in situ of the cervix or breast.
  8. Patients must have no serious medical illness, other that treated by this study, which would limit survival to less than 1 month or psychiatric illness which would limit informed consent.
  9. Patients must not have peripheral neuropathy > grade 2.
  10. Required Cardiac Parameters: Patients must not have had a history of New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina or CVA within 6 months of protocol registration. LVEF > 50% by MUGA or ECHO.
  11. Patients must not have history of PR prolongation or AV block
  12. Required laboratory parameters: Patients must have serum creatinine < 1.5 mg/dl.
  13. Patients must have adequate hematologic functions: granulocytes > 1500/mm^3 and platelets > 100,000/mm^3
  14. Patients must have adequate hepatocellular function: SGOT (AST) and SGPT (ALT) < 1.5 x upper limit of normal (unless liver is involved by tumor, in which case SGOT (AST) and SGPT (ALT) can be < 2.0 x upper limit of normal)
  15. Patients must have no history of prior therapy with seliciclib.
  16. Patients must not have received a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 640 mg/m^2. Patients who have received >240 mg/m^2 of doxorubicin or >400 mg/m^2 of epirubicin should be advised to undergo evaluation of left ventricular ejection fraction (LVEF) with echocardiogram (ECHO) or gated heart scan (MUGA) prior to initiating therapy.
  17. Concurrent use of hormonal therapy is not permitted. Concurrent radiation therapy is not permitted.
  18. Patients must not have had prior organ allograft or require immunosuppressive therapy.
  19. Patients must have completed and recovered from the effects of prior chemotherapy (</= grade 2 toxicity).
  20. Patients must have received at least one prior chemotherapy regimen for metastatic disease. Progression within 6 months of adjuvant chemotherapy will be considered equivalent to one prior chemotherapy for metastatic disease.

Exclusion Criteria:

1) None.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01333423

Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Stacy Moulder, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01333423     History of Changes
Other Study ID Numbers: 2011-0013, 1RO1CA152228-01A1
Study First Received: April 8, 2011
Last Updated: June 22, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Breast Cancer
Metastatic Triple Negative
ER/PR/HER2 negative
Locally advanced
Stage IV
Metastatic
Seliciclib
Liposomal Doxorubicin
Doxil
Doxorubicin Hydrochloride (Liposomal)

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Doxorubicin
Liposomal doxorubicin
Roscovitine
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 22, 2014