Trial Outcomes & Findings for Therapy for Locally Advanced Breast Cancer Using Doxil, Paclitaxel, and Cyclophosphamide With Avastin (NCT NCT00635050)

NCT ID: NCT00635050

Last Updated: 2016-07-14

Results Overview

Results of the pathologic evaluation of the surgical specimen(s) from operation (segmental or total mastectomy) will be used to report the overall complete pathological response rate. Criteria used were those described by Kaufmann et al, Journal of Clinical Oncology 2003; 21(13):2600-2608. The definition of pCR used from this source was absence of invasive cancer in both resected breast tissue and in resected axillary nodes.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 32 participants
• Primary outcome timeframe: After completion of at least 8 of the 9 chemotherapy doses and operation.
• Results posted on: 2016-07-14

Participant Flow

Participant milestones

Measure	Doxil, Paclitaxel, Cyclophosphamide + Avastin Two stage phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil, paclitaxel and cyclophosphamide with concurrent Avastin in patients with locally advanced invasive breast cancer. Doxil, Paclitaxel, Cyclophosphamide, Avastin: Regimen A: Sequential Doxil 25 mg/m2 every 2 weeks for 3 doses, followed by paclitaxel 175 mg/m2 i.v. every 2 weeks for 3 doses, then cyclophosphamide 600 mg/M 2 i.v. every 2 weeks for 3 doses. Avastin 10 mg/kg i.v. every 2 weeks will be given concurrently with all 3 agents. Patients who experience \<pCR to primary chemotherapy will receive an additional year of Avastin at the same dose equivalent beginning 6-8 weeks after definitive operation. Regimen B: Sequential Doxil 30 mg/m2 every 2 weeks for 3 doses will be followed by paclitaxel 175 mg/m2 i.v. every 2 weeks for 3 doses, then by cyclophosphamide 600 mg/m 2 i.v. every 2 weeks for 3 doses. Avastin 10 mg/kg i.v. every 2 week
Overall Study STARTED	32
Overall Study COMPLETED	31
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

Doxil, Paclitaxel, Cyclophosphamide + Avastin Two stage phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil, paclitaxel and cyclophosphamide with concurrent Avastin in patients with locally advanced invasive breast cancer. Doxil, Paclitaxel, Cyclophosphamide, Avastin: Regimen A: Sequential Doxil 25 mg/m2 every 2 weeks for 3 doses, followed by paclitaxel 175 mg/m2 i.v. every 2 weeks for 3 doses, then cyclophosphamide 600 mg/M 2 i.v. every 2 weeks for 3 doses. Avastin 10 mg/kg i.v. every 2 weeks will be given concurrently with all 3 agents. Patients who experience \<pCR to primary chemotherapy will receive an additional year of Avastin at the same dose equivalent beginning 6-8 weeks after definitive operation. Regimen B: Sequential Doxil 30 mg/m2 every 2 weeks for 3 doses will be followed by paclitaxel 175 mg/m2 i.v. every 2 weeks for 3 doses, then by cyclophosphamide 600 mg/m 2 i.v. every 2 weeks for 3 doses. Avastin 10 mg/kg i.v. every 2 week

Overall Study Withdrawal by Subject

1

Baseline Characteristics

Therapy for Locally Advanced Breast Cancer Using Doxil, Paclitaxel, and Cyclophosphamide With Avastin

Baseline characteristics by cohort

Measure	Doxil, Paclitaxel, Cyclophosphamide + Avastin n=32 Participants Two stage phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil, paclitaxel and cyclophosphamide with concurrent Avastin in patients with locally advanced invasive breast cancer. Regimen A: Sequential Doxil 25 mg/m2 every 2 weeks for 3 doses, then paclitaxel 175 mg/m2 i.v. every 2 weeks for 3 doses, then cyclophosphamide 600 mg/M 2 i.v. every 2 weeks for 3 doses. Avastin 10 mg/kg i.v. every 2 weeks will be given concurrently with all 3 agents. Patients who experience \<pCR to chemotherapy will receive an additional year of Avastin at the same dose equivalent starting 6-8 weeks after operation. Regimen B: Identical to Regimen A except that the dose of Doxil will be 30 mg/m2.
Age, Continuous	49 years n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	32 participants n=5 Participants

PRIMARY outcome

Timeframe: After completion of at least 8 of the 9 chemotherapy doses and operation.

Population: Intention to treat, i.e., all participants entered were included in the analysis.

Results of the pathologic evaluation of the surgical specimen(s) from operation (segmental or total mastectomy) will be used to report the overall complete pathological response rate. Criteria used were those described by Kaufmann et al, Journal of Clinical Oncology 2003; 21(13):2600-2608. The definition of pCR used from this source was absence of invasive cancer in both resected breast tissue and in resected axillary nodes.

Outcome measures

Measure

Doxil, Paclitaxel, Cyclophosphamide + Avastin n=32 Participants Two stage phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil, paclitaxel and cyclophosphamide with concurrent Avastin in patients with advanced invasive breast cancer. Regimen A: Doxil 25 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3 . Patients who experience \<pCR to primary chemotherapy will receive an additional year of Avastin 15 mg/kg iv every 3 weeks, beginning 6-8 weeks after operation. Regimen B: Identical to Regimen A except that the Doxil dose was 30 mg/M2 iv every 2 weeks x 3.

Rate of Achievement of Pathological Complete Response (pCR)

9 pathology specimens from participants

SECONDARY outcome

Timeframe: Prior to treatment and at completion of chemotherapy

Left ventricular ejection fraction (LVEF) measurements and clinical examination at baseline and at end of therapy will be used.

Outcome measures

Measure

Doxil, Paclitaxel, Cyclophosphamide + Avastin n=31 Participants Two stage phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil, paclitaxel and cyclophosphamide with concurrent Avastin in patients with advanced invasive breast cancer. Regimen A: Doxil 25 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3 . Patients who experience \<pCR to primary chemotherapy will receive an additional year of Avastin 15 mg/kg iv every 3 weeks, beginning 6-8 weeks after operation. Regimen B: Identical to Regimen A except that the Doxil dose was 30 mg/M2 iv every 2 weeks x 3.

Number of Participant With Clinical or Subclinical Cardiotoxicity

0 participants

SECONDARY outcome

Timeframe: 5 years

Population: operative specimens after treatment of participants

Progression free survival (PFS) will be defined as survival without local recurrence of breast cancer and without the development of distant metastasis. Death from any cause will be included as an event. The Kaplan-Meier nonparametric method will be used to estimate progression free survival.

Outcome measures

Measure

Doxil, Paclitaxel, Cyclophosphamide + Avastin n=32 Participants Two stage phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil, paclitaxel and cyclophosphamide with concurrent Avastin in patients with advanced invasive breast cancer. Regimen A: Doxil 25 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3 . Patients who experience \<pCR to primary chemotherapy will receive an additional year of Avastin 15 mg/kg iv every 3 weeks, beginning 6-8 weeks after operation. Regimen B: Identical to Regimen A except that the Doxil dose was 30 mg/M2 iv every 2 weeks x 3.

Calculate Progression Free Survival

22 participants

SECONDARY outcome

Timeframe: Baseline, every 2 weeks during treatment, and at completion of therapy. Every 3 weeks during postoperative Avastin

patients who receive any treatment drugs will be included for toxicity evaluation. Adverse events will be summarized with frequencies and proportions of study participants exhibiting adverse events. The severity of adverse events (none, mild, moderate, severe) and their relationship to the product will be presented.

Outcome measures

Measure

Doxil, Paclitaxel, Cyclophosphamide + Avastin n=32 Participants Two stage phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil, paclitaxel and cyclophosphamide with concurrent Avastin in patients with advanced invasive breast cancer. Regimen A: Doxil 25 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3 . Patients who experience \<pCR to primary chemotherapy will receive an additional year of Avastin 15 mg/kg iv every 3 weeks, beginning 6-8 weeks after operation. Regimen B: Identical to Regimen A except that the Doxil dose was 30 mg/M2 iv every 2 weeks x 3.

Assess Toxicities of Regimen Including Hand Foot Syndrome

23 participants

Adverse Events

Doxil, Paclitaxel, Cyclophosphamide + Avastin

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure

Doxil, Paclitaxel, Cyclophosphamide + Avastin n=32 participants at risk Two staged phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil, paclitaxel and cyclophosphamide with concurrent Avastin in patients with advanced invasive breast cancer. Doxil, Paclitaxel, Cyclophosphamide, Avastin: Regimen A: Sequential Doxil 25 mg/m2 every 2 weeks for 3 doses will be followed by paclitaxel 175 mg/m2 i.v. every 2 weeks for 3 doses, then by cyclophosphamide 600 mg/M 2 i.v. every 2 weeks for 3 doses. Avastin 10 mg/kg i.v. every 2 weeks will be given concurrently with all 3 agents. Patients who experience \<pCR to primary chemotherapy will receive an additional year of Avastin at the same dose equivalent beginning 6-8 weeks after definitive operation. Regimen B: Sequential Doxil 30 mg/m2 every 2 weeks for 3 doses will be followed by paclitaxel 175 mg/m2 i.v. every 2 weeks for 3 doses, then by cyclophosphamide 600 mg/m 2 i.v. every 2 weeks for 3 doses. Avastin 10 mg/kg i.v. every 2 week

Skin and subcutaneous tissue disorders hospitalization

3.1% 1/32 • Number of events 1 • At baseline, every 2 weeks during chemotherapy and Avastin, every 3 weeks during postoperative Avastin, every 6 months afterward though 5 years of followup, then annually to 10 years of followup.

Other adverse events

Measure	Doxil, Paclitaxel, Cyclophosphamide + Avastin n=32 participants at risk Two staged phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil, paclitaxel and cyclophosphamide with concurrent Avastin in patients with advanced invasive breast cancer. Doxil, Paclitaxel, Cyclophosphamide, Avastin: Regimen A: Sequential Doxil 25 mg/m2 every 2 weeks for 3 doses will be followed by paclitaxel 175 mg/m2 i.v. every 2 weeks for 3 doses, then by cyclophosphamide 600 mg/M 2 i.v. every 2 weeks for 3 doses. Avastin 10 mg/kg i.v. every 2 weeks will be given concurrently with all 3 agents. Patients who experience \<pCR to primary chemotherapy will receive an additional year of Avastin at the same dose equivalent beginning 6-8 weeks after definitive operation. Regimen B: Sequential Doxil 30 mg/m2 every 2 weeks for 3 doses will be followed by paclitaxel 175 mg/m2 i.v. every 2 weeks for 3 doses, then by cyclophosphamide 600 mg/m 2 i.v. every 2 weeks for 3 doses. Avastin 10 mg/kg i.v. every 2 week
Skin and subcutaneous tissue disorders rash	53.1% 17/32 • Number of events 17 • At baseline, every 2 weeks during chemotherapy and Avastin, every 3 weeks during postoperative Avastin, every 6 months afterward though 5 years of followup, then annually to 10 years of followup.
Skin and subcutaneous tissue disorders hand-foot syndrome	71.9% 23/32 • Number of events 23 • At baseline, every 2 weeks during chemotherapy and Avastin, every 3 weeks during postoperative Avastin, every 6 months afterward though 5 years of followup, then annually to 10 years of followup.
Gastrointestinal disorders mucositis	3.1% 1/32 • Number of events 1 • At baseline, every 2 weeks during chemotherapy and Avastin, every 3 weeks during postoperative Avastin, every 6 months afterward though 5 years of followup, then annually to 10 years of followup.
Renal and urinary disorders proteinuria	3.1% 1/32 • Number of events 1 • At baseline, every 2 weeks during chemotherapy and Avastin, every 3 weeks during postoperative Avastin, every 6 months afterward though 5 years of followup, then annually to 10 years of followup.
General disorders hypertension	21.9% 7/32 • Number of events 7 • At baseline, every 2 weeks during chemotherapy and Avastin, every 3 weeks during postoperative Avastin, every 6 months afterward though 5 years of followup, then annually to 10 years of followup.
Blood and lymphatic system disorders neutropenia	18.8% 6/32 • Number of events 6 • At baseline, every 2 weeks during chemotherapy and Avastin, every 3 weeks during postoperative Avastin, every 6 months afterward though 5 years of followup, then annually to 10 years of followup.

Additional Information

John Carpenter, M.D.

UAB

Phone: 205-910-8886 or 205-934-2084

Email: jtc4321@bellsouth.net

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place