Ixabepilone + Carboplatin Metastatic Breast Cancer

• ClinicalTrials.gov Identifier: NCT01075100
• Recruitment Status: Completed
• First Posted: February 24, 2010
• Results First Posted: December 7, 2016
• Last Update Posted: December 7, 2016
• Sponsor: US Oncology Research
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): US Oncology Research

Tracking Information

• First Submitted Date: January 14, 2010
• First Posted Date: February 24, 2010
• Results First Submitted Date: January 12, 2016
• Results First Posted Date: December 7, 2016
• Last Update Posted Date: December 7, 2016
• Study Start Date: January 2010
• Actual Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 14, 2016)

Objective Response Rate (ORR) [ Time Frame: 24 months ]

Evaluate the objective response rate calculated as CR+ PR in the population evaluable for response, as well as the 2 subgroups (hormone receptor positive [ER+/PR+/HER2-, ER+/PR-/HER2-, ER-/PR+/HER2-]) and ER-/PR-HER2-, separately). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

• Original Primary Outcome Measures (submitted: February 23, 2010): Evaluate the objective response rate calculated as CR+ PR in the population evaluable for response, as well as the 2 subgroups (hormone receptor positive [ER+/PR+/HER2-, ER+/PR-/HER2-, ER-/PR+/HER2-]) and ER-/PR-HER2-, separately). [ Time Frame: 24 months ]

Current Secondary Outcome Measures (submitted: October 14, 2016)

• Clinical Benefit Rate (CBR) [ Time Frame: 24 months ]
  Clinical benefit rate (CBR) defined as objective response rate (ORR, CR + PR) + SD >= 6 months
• Progression-free Survival (PFS) [ Time Frame: 24 months ]
  PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
• Overall Survival (OS) [ Time Frame: 24 months ]
  OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.
• Time to Response [ Time Frame: 24 months ]
  For patients who achieve a major objective response (CR or PR) the time to response will be assessed as the date of registration to the date of response.
• Duration of Response [ Time Frame: 30 months ]
  The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented.

Original Secondary Outcome Measures (submitted: February 23, 2010)

• Clinical benefit rate (CBR) defined as overall response rate (ORR) [complete response + partial response (CR + PR)] + SD > 6 months [ Time Frame: 24 months ]
• Progression-free survival (PFS) [ Time Frame: 24 months ]
• Overall survival (OS) [ Time Frame: 24 months ]
• Duration of responses, duration of stable disease, time to response and drug toxicity [ Time Frame: 24 months ]
  Toxicities will be graded according to the NCI Common Terminology Criteria for Adverse Events (version 4.0). Subjects enrolled in this study will be carefully monitored during the entire treatment phase and will be followed as is appropriate. Incidence and type of adverse events, including serious adverse events, will be tabulated and summarized using descriptive statistics. Adverse events that are unrelated to treatment and that occur >30 days after the administration of treatment will not be reported or analyzed.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ixabepilone + Carboplatin Metastatic Breast Cancer
• Official Title: Phase II Trial of Ixabepilone Plus Carboplatin in Patients With Metastatic Breast Cancer: The ECLIPSE Study
• Brief Summary: Ixabepilone adds significantly to the antitumor effectiveness of capecitabine in both ER+ and triple negative breast cancer. Ixabepilone has substantial antitumor activity in taxane-refractory patients and novel combinations are needed in this poor prognosis population. Carboplatin in combination with gemcitabine or paclitaxel has activity in metastatic breast cancer (MBC); there is also demonstrated activity of the gemcitabine/carboplatin combination in the ER+ versus triple negative subsets. A Phase I study of ixabepilone plus carboplatin in solid tumor patients demonstrated the safety of this combination at the doses and schedule proposed for this Phase II trial (BMS data on file).
• Detailed Description: This is a Phase II, open label, nonrandomized, parallel, noncomparative, study of 2 groups (as stratified below). All patients will receive ixabepilone 20 mg/m2 on Days 1 and 8 and carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle. Patients will be stratified by either hormone receptor positive [ER+/PR+/HER2-, ER+/PR-/HER2-, ER-/PR+/HER2-]- (n=50) or triples negative ER-/PR-/HER2- (n=53). If one group fulfills their accrual goal first, registration into that strata will be stopped and only patients meeting stratification requirements for the other group will be registered.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Breast Cancer

Intervention

• Drug: Ixabepilone
  20 mg/m2 on Days 1 and 8
  Other Names:

  • Ixempra
  • azaepothilone B
• Drug: Carboplatin
  carboplatin AUC=2.5 on Days 1 and 8
  Other Name: Paraplatin

Study Arms

Experimental: Weekly Ixabepilone +carboplatin

Subjects will receive ixabepilone and carboplatin on Days 1 and 8 of each 21-day cycle.

Interventions:

• Drug: Ixabepilone
• Drug: Carboplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 23, 2010): 103
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: June 2013
• Actual Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Male or female patients will be eligible for inclusion in this study if they meet all of the following criteria:

1. Has measurable metastatic and or locally unresectable breast cancer with documented HER2 negative (-) disease
2. Has at least 1 measurable lesion per RECIST criteria (lesions that can be accurately measured in at least 1 dimension (longest diameter (LD) to be recorded) as ≥20 mm with conventional techniques (CT, MRI, X-ray) or as ≥10 mm with spiral CT scan). Irradiated lesions cannot be used to assess response but can be used to assess progression.

3. Has received up to 2 (0 to 2) prior chemotherapy regimens for metastatic disease with the following conditions:

   •Has had no prior treatment with ixabepilone or platinum agents

4. Has had no adjuvant chemotherapy within the 6 months prior to study, but may have received prior anthracyclines and/or taxanes as adjuvant chemotherapy
5. 3 weeks or more have elapsed since last chemotherapy treatment and any related toxicities have resolved to <Grade 1; at least 30 days must have passed since any investigational product has been administered and associated toxicities must have resolved to <Grade 1 (if applicable).
6. Has an ECOG Performance Status (PS) 0-2
7. Is ≥18 years of age
8. Has a life expectancy of at least 12 weeks

9. Has laboratory values of:

   White blood cell (WBC) count ≥3000 x 106/L Absolute neutrophil count (ANC) ≥1500 x 106/L Hemoglobin ≥9 g/dL Total bilirubin ≤1x upper limit of normal (ULN) AST and ALT ≤2.5 x ULN Alkaline phosphatase ≤2.5 x ULN; up to 5xULN if elevation is due to bone disease Serum creatinine ≤1.5 mg/dL Calculated creatinine clearance >50 mL/min (based on Cockroft and Gault method [Appendix III]) Platelet count ≥100,000 x 106/L

10. If patient has had radiation therapy, it has been completed >3 weeks prior to the start of study treatment. NOTE: Previously irradiated lesions will not be evaluable. However, these patients will still be eligible.
11. Has a negative serum pregnancy test within 7 calendar days prior to registration (female patients of childbearing potential [not surgically sterilized and between menarche and 1 year postmenopause
12. If fertile, patient (male or female) has agreed to use an acceptable method of birth control to avoid pregnancy for the duration of the study and for a period of 3 months thereafter
13. Has signed the most recent Patient Informed Consent Form
14. Has signed a Patient Authorization Form Note: Having tissue available is not an inclusion criterion in this study; however, available tissue will be collected (see Section 8) if possible.

Exclusion Criteria:

A patient will be excluded from this study if he or she meets any of the following criteria:

1. Had prior treatment with ixabepilone or other epothilones
2. Had prior radiation to ≥30% of major bone marrow containing areas (pelvis, lumbar spine)
3. Has ER+ and/or PR+ disease that has not progressed on hormone therapy, unless the patient has life-threatening or rapidly progressing visceral disease
4. Has HER2+ disease (IHC staining of 3+ [uniform, intense membrane staining of >30% of invasive tumor cells]), a FISH result of more than 6 HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals of >2.2)
5. Has only lytic bone disease or nonmeasurable disease only
6. Has a known, prior, severe (NCI CTCAE Grade 3-4) history of hypersensitivity reaction to a drug formulated in Cremophor®EL (polyoxyethylated castor oil) or has history of severe allergic reactions to cisplatin or other platinum-containing compounds
7. Has been treated previously with a platinum-containing agent
8. Is receiving concurrent immunotherapy, hormonal therapy, or radiation therapy. Washout periods for these prior therapies are specified in Section 5.
9. Is receiving concurrent investigational therapy or has received such therapy within the 30 days prior to dosing Day 1
10. Has neuropathy (motor or sensory) >Grade 1
11. Has evidence of CNS involvement requiring radiation or steroid treatment. Patients with stable brain metastases who are off steroids at least 2 weeks are eligible.
12. Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection
13. Has clinically relevant coagulopathy either secondary to hepatic dysfunction or an underlying condition requiring therapeutic anticoagulation (specifically, A-fib, history of DVT). A daily aspirin or Plavix for CAD are permitted.
14. Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the diagnosis or assessment of any of the study drugs
15. Is a pregnant or breast feeding woman
16. Is unable to comply with the requirements of the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01075100
• Other Study ID Numbers: 08007
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: US Oncology Research
• Study Sponsor: US Oncology Research
• Collaborators: Bristol-Myers Squibb

Investigators

• Principal Investigator: Cynthia R Osborne, MD; US Oncology

• PRS Account: US Oncology Research
• Verification Date: October 2016