Trial Outcomes & Findings for Dose Dense TC + Pegfilgrastim Support for Breast Cancer (NCT NCT01671319)

Last Updated: 2019-11-27

Results Overview

Evaluate feasibility of delivering 4 cycles (1 cycle = 2 weeks) of docetaxel and cyclophosphamide (TC) on a dose-dense (q2week) schedule with pegfilgrastim support. This regimen will be referred to as dose-dense (dd)TC. Feasibility defined by at least 60% of patients receiving 90% of the total dose of therapy within 10 weeks.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

4 cycles each 2 weeks in length for a total of 8 weeks, up to 10 weeks

Results posted on

2019-11-27

Participant Flow

The study was performed through the Wisconsin Oncology Network, a regional oncology network, at a combination of academic and community practice sites. Patients were enrolled between June 2011 and June 2012.

Participant milestones

Participant milestones
Measure	Dose Dense TC + Pegfilgrastim Docetaxel + Cyclophosphamide chemotherapy given every 2 weeks x 4 cycles plus pegfilgrastim given 24-48 hours post day 1 of each cycle docetaxel + cyclophosphamide + pegfilgrastim: docetaxel 75 mg/m2 + cyclophosphamide 600 mg/m2 IV every 2 weeks x 4 cycles plus pegfilgrastim 6mg sq 24-48 hours post day 1 of each cycle
Overall Study STARTED	42
Overall Study COMPLETED	41
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Dense TC + Pegfilgrastim Docetaxel + Cyclophosphamide chemotherapy given every 2 weeks x 4 cycles plus pegfilgrastim given 24-48 hours post day 1 of each cycle docetaxel + cyclophosphamide + pegfilgrastim: docetaxel 75 mg/m2 + cyclophosphamide 600 mg/m2 IV every 2 weeks x 4 cycles plus pegfilgrastim 6mg sq 24-48 hours post day 1 of each cycle
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Dose Dense TC + Pegfilgrastim Support for Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Dense TC + Pegfilgrastim n=41 Participants Docetaxel + Cyclophosphamide chemotherapy given every 2 weeks x 4 cycles plus pegfilgrastim given 24-48 hours post day 1 of each cycle docetaxel + cyclophosphamide + pegfilgrastim: docetaxel 75 mg/m2 + cyclophosphamide 600 mg/m2 IV every 2 weeks x 4 cycles plus pegfilgrastim 6mg sq 24-48 hours post day 1 of each cycle
Age, Continuous	54 years n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	39 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	41 participants n=5 Participants
Pre- vs. Postmenopausal Premenopausal	15 Participants n=5 Participants
Pre- vs. Postmenopausal Postmenopausal	26 Participants n=5 Participants
Staging Criteria Node-negative	30 Participants n=5 Participants
Staging Criteria Node-positive	10 Participants n=5 Participants
Staging Criteria Nodes unknown	1 Participants n=5 Participants
Staging Criteria T1	21 Participants n=5 Participants
Staging Criteria T2	20 Participants n=5 Participants
Receptor Status Hormone receptor-postive	29 Participants n=5 Participants
Receptor Status HER2-positive	1 Participants n=5 Participants
Receptor Status Triple negative	11 Participants n=5 Participants
Final Surgery Mastectomy	20 Participants n=5 Participants
Final Surgery Breast conservation	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 cycles each 2 weeks in length for a total of 8 weeks, up to 10 weeks

Population: Of 42 participants, 41 were evaluable for outcome measure analysis.

Outcome measures

Outcome measures
Measure	Dose Dense TC + Pegfilgrastim n=41 Participants Docetaxel + Cyclophosphamide chemotherapy given every 2 weeks x 4 cycles plus pegfilgrastim given 24-48 hours post day 1 of each cycle docetaxel + cyclophosphamide + pegfilgrastim: docetaxel 75 mg/m2 + cyclophosphamide 600 mg/m2 IV every 2 weeks x 4 cycles plus pegfilgrastim 6mg sq 24-48 hours post day 1 of each cycle
Feasibility for Dose-dense TC Therapy: Number of Participants Receiving at Least 90% of Total Dose of Therapy	37 participants

SECONDARY outcome

Timeframe: Up to 10 weeks

Population: Of 42 participants, 41 were evaluable for outcome measure analysis.

Neutropenic fever was anticipated to be a clinically significant toxicity that would limit the maximal density of TC therapy.

Outcome measures

Outcome measures
Measure	Dose Dense TC + Pegfilgrastim n=41 Participants Docetaxel + Cyclophosphamide chemotherapy given every 2 weeks x 4 cycles plus pegfilgrastim given 24-48 hours post day 1 of each cycle docetaxel + cyclophosphamide + pegfilgrastim: docetaxel 75 mg/m2 + cyclophosphamide 600 mg/m2 IV every 2 weeks x 4 cycles plus pegfilgrastim 6mg sq 24-48 hours post day 1 of each cycle
Incidence of Febrile Neutropenia	1 Participants

SECONDARY outcome

Timeframe: Up to 10 weeks

Population: Of 42 participants, 41 were evaluable for outcome measure analysis.

Neuropathy was anticipated to be a clinically significant toxicity that would limit the maximal density of TC therapy.

Outcome measures

Outcome measures
Measure	Dose Dense TC + Pegfilgrastim n=41 Participants Docetaxel + Cyclophosphamide chemotherapy given every 2 weeks x 4 cycles plus pegfilgrastim given 24-48 hours post day 1 of each cycle docetaxel + cyclophosphamide + pegfilgrastim: docetaxel 75 mg/m2 + cyclophosphamide 600 mg/m2 IV every 2 weeks x 4 cycles plus pegfilgrastim 6mg sq 24-48 hours post day 1 of each cycle
Incidence of Neuropathy Sensory neuropathy	5 Participants
Incidence of Neuropathy Motor neuropathy	1 Participants
Incidence of Neuropathy No incidence of neuropathy	35 Participants

Adverse Events

Dose Dense TC + Pegfilgrastim

Serious events: 4 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose Dense TC + Pegfilgrastim n=42 participants at risk Docetaxel + Cyclophosphamide chemotherapy given every 2 weeks x 4 cycles plus pegfilgrastim given 24-48 hours post day 1 of each cycle docetaxel + cyclophosphamide + pegfilgrastim: docetaxel 75 mg/m2 + cyclophosphamide 600 mg/m2 IV every 2 weeks x 4 cycles plus pegfilgrastim 6mg sq 24-48 hours post day 1 of each cycle
Infections and infestations Febrile neutropenia	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Perforation, GI	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Skin and subcutaneous tissue disorders Rash/desquamation	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Nervous system disorders Syncope	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.

Other adverse events

Other adverse events
Measure	Dose Dense TC + Pegfilgrastim n=42 participants at risk Docetaxel + Cyclophosphamide chemotherapy given every 2 weeks x 4 cycles plus pegfilgrastim given 24-48 hours post day 1 of each cycle docetaxel + cyclophosphamide + pegfilgrastim: docetaxel 75 mg/m2 + cyclophosphamide 600 mg/m2 IV every 2 weeks x 4 cycles plus pegfilgrastim 6mg sq 24-48 hours post day 1 of each cycle
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	14.3% 6/42 • Number of events 11 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Metabolism and nutrition disorders Alkaline phosphatase	21.4% 9/42 • Number of events 10 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	7.1% 3/42 • Number of events 3 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Immune system disorders Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	4.8% 2/42 • Number of events 2 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Metabolism and nutrition disorders ALT, SGPT (serum glutamic pyruvic transaminase)	38.1% 16/42 • Number of events 20 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Anorexia	26.2% 11/42 • Number of events 13 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Musculoskeletal and connective tissue disorders Arthritis (non-septic)	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Metabolism and nutrition disorders AST, SGOT(serum glutamic oxaloacetic transaminase)	21.4% 9/42 • Number of events 11 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Ear and labyrinth disorders Auditory/Ear - Ear pain	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Immune system disorders Autoimmune reaction	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Metabolism and nutrition disorders Bilirubin (hyperbilirubinemia)	4.8% 2/42 • Number of events 2 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Skin and subcutaneous tissue disorders Bruising (in absence of Grade 3 or 4 thrombocytopenia)	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Metabolism and nutrition disorders Calcium, serum-high (hypercalcemia)	4.8% 2/42 • Number of events 3 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Constipation	31.0% 13/42 • Number of events 13 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 3/42 • Number of events 3 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Metabolism and nutrition disorders Creatinine	11.9% 5/42 • Number of events 5 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Immune system disorders Cytokine release syndrome/acute infusion reaction	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Dehydration	4.8% 2/42 • Number of events 2 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Skin and subcutaneous tissue disorders Dermatology/Skin	19.0% 8/42 • Number of events 9 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Diarrhea	33.3% 14/42 • Number of events 21 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Distension/bloating, abdominal	4.8% 2/42 • Number of events 2 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Nervous system disorders Dizziness	9.5% 4/42 • Number of events 4 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Eye disorders Dry eye syndrome	4.8% 2/42 • Number of events 3 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Dry mouth/salivary gland (xerostomia)	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Skin and subcutaneous tissue disorders Dry skin	14.3% 6/42 • Number of events 7 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	11.9% 5/42 • Number of events 5 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Endocrine disorders Edema: limb	14.3% 6/42 • Number of events 6 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
General disorders Fatigue (asthenia, lethargy, malaise)	81.0% 34/42 • Number of events 71 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Infections and infestations Febrile neutropenia	4.8% 2/42 • Number of events 2 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
General disorders Fever	9.5% 4/42 • Number of events 4 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Skin and subcutaneous tissue disorders Flushing	9.5% 4/42 • Number of events 4 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Gastritis (including bile reflux gastritis)	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Gastrointestinal	7.1% 3/42 • Number of events 4 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	33.3% 14/42 • Number of events 32 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Skin and subcutaneous tissue disorders Hair loss/alopecia (scalp or body)	50.0% 21/42 • Number of events 26 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Heartburn/dyspepsia	11.9% 5/42 • Number of events 6 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Blood and lymphatic system disorders Hemoglobin	76.2% 32/42 • Number of events 59 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Blood and lymphatic system disorders Hemorrhage, pulmonary/upper respiratory - Nose	4.8% 2/42 • Number of events 3 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Blood and lymphatic system disorders Hemorrhage/Bleeding	4.8% 2/42 • Number of events 3 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Endocrine disorders Hot flashes/flushes	9.5% 4/42 • Number of events 5 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
General disorders Hypothermia	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Infections and infestations Infection	19.0% 8/42 • Number of events 9 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
General disorders Injection site reaction/extravasation changes	14.3% 6/42 • Number of events 9 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
General disorders Insomnia	11.9% 5/42 • Number of events 5 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Reproductive system and breast disorders Irregular menses (change from baseline)	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Blood and lymphatic system disorders Leukocytes (total WBC)	9.5% 4/42 • Number of events 4 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Blood and lymphatic system disorders Lymphopenia	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Nervous system disorders Mood alteration - Anxiety	9.5% 4/42 • Number of events 5 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam) - Oral cavity	40.5% 17/42 • Number of events 21 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) - Extremity-lower	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Skin and subcutaneous tissue disorders Nail changes	38.1% 16/42 • Number of events 17 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Respiratory, thoracic and mediastinal disorders Nasal cavity/paranasal sinus reactions	7.1% 3/42 • Number of events 3 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Nausea	42.9% 18/42 • Number of events 29 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Nervous system disorders Neurology - Other	9.5% 4/42 • Number of events 4 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Nervous system disorders Neuropathy: motor	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Nervous system disorders Neuropathy: sensory	52.4% 22/42 • Number of events 30 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	9.5% 4/42 • Number of events 5 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Eye disorders Ocular/Visual - Itchy eyes	4.8% 2/42 • Number of events 2 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
General disorders Pain	78.6% 33/42 • Number of events 77 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Cardiac disorders Palpitations	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Perforation, GI - Colon	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Vascular disorders Phlebitis (including superficial thrombosis)	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Metabolism and nutrition disorders Phosphate, serum-low (hypophosphatemia)	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Skin and subcutaneous tissue disorders Photosensitivity	4.8% 2/42 • Number of events 2 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Blood and lymphatic system disorders Platelets	26.2% 11/42 • Number of events 15 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory - Other	7.1% 3/42 • Number of events 4 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Skin and subcutaneous tissue disorders Rash/desquamation	19.0% 8/42 • Number of events 14 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	14.3% 6/42 • Number of events 7 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Skin and subcutaneous tissue disorders Rash: erythema multiforme (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)	9.5% 4/42 • Number of events 5 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Skin and subcutaneous tissue disorders Rash: hand-foot skin reaction	28.6% 12/42 • Number of events 14 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Renal and urinary disorders Renal/Genitourinary - Dysuria	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	7.1% 3/42 • Number of events 4 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Cardiac disorders Supraventricular and nodal arrhythmia - Sinus bradycardia	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Cardiac disorders Supraventricular and nodal arrhythmia - Sinus tachycardia	4.8% 2/42 • Number of events 2 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
General disorders Sweating (diaphoresis)	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Taste alteration (dysgeusia)	26.2% 11/42 • Number of events 12 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Nervous system disorders Tremor	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Renal and urinary disorders Urinary frequency/urgency	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Reproductive system and breast disorders Vaginal mucositis	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Eye disorders Vision-blurred vision	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Respiratory, thoracic and mediastinal disorders Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	2.4% 1/42 • Number of events 2 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Gastrointestinal disorders Vomiting	4.8% 2/42 • Number of events 3 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Eye disorders Watery eye (epiphora, tearing)	35.7% 15/42 • Number of events 16 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
General disorders Weight gain	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
General disorders Weight loss	2.4% 1/42 • Number of events 1 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.
Skin and subcutaneous tissue disorders Wound complication, non-infectious	7.1% 3/42 • Number of events 3 Toxicity assessments were made one day 1 of each cycle, and as indicated clinically.

Additional Information

Dr. Amyé Tevaarwerk

University of Wisconsin Carbone Cancer Center

Phone: 608-262-2837

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place