Trial Outcomes & Findings for Neoadjuvant Platinum-based Chemoradiation Therapy for Locally Advanced Triple Negative Breast Cancer (NCT NCT01167192)

Last Updated: 2016-12-30

Results Overview

* Complete response (CR) = disappearance of all target lesions, disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR) = at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Prior to surgery (approximately 12-16 weeks from registration)

Results posted on

2016-12-30

Participant Flow

The study opened to enrollment on 02/04/2011 and closed to enrollment on 09/10/2013.

Participant milestones

Participant milestones
Measure	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation Cisplatin 75 mg/m\^2 IV every 21 days for 4 cycles or Carboplatin AUC 6 IV every 21 days for 4 cycles. Radiation beginning cycle 2 day 1 daily for 5-6 weeks 45-50 Gy. Recommended mastectomy Recommended adjuvant chemotherapy -Doxorubicin 60 mg/m\^2 and cyclophosphamide 600 mg/m\^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m\^2 for 14 days for 4 cycles)
Overall Study STARTED	10
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation Cisplatin 75 mg/m\^2 IV every 21 days for 4 cycles or Carboplatin AUC 6 IV every 21 days for 4 cycles. Radiation beginning cycle 2 day 1 daily for 5-6 weeks 45-50 Gy. Recommended mastectomy Recommended adjuvant chemotherapy -Doxorubicin 60 mg/m\^2 and cyclophosphamide 600 mg/m\^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m\^2 for 14 days for 4 cycles)
Overall Study Adverse Event	1
Overall Study Death	1
Overall Study Withdrawal by Subject	1
Overall Study Insurance denial	1

Baseline Characteristics

Neoadjuvant Platinum-based Chemoradiation Therapy for Locally Advanced Triple Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation n=10 Participants Cisplatin 75 mg/m\^2 IV every 21 days for 4 cycles or Carboplatin AUC 6 IV every 21 days for 4 cycles. Radiation beginning cycle 2 day 1 daily for 5-6 weeks 45-50 Gy. Recommended mastectomy Recommended adjuvant chemotherapy -Doxorubicin 60 mg/m\^2 and cyclophosphamide 600 mg/m\^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m\^2 for 14 days for 4 cycles)
Age, Continuous	48 years n=5 Participants
Gender Female	10 Participants n=5 Participants
Gender Male	0 Participants n=5 Participants
Region of Enrollment United States	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: Prior to surgery (approximately 12-16 weeks from registration)

Population: 1 patient was removed from study due to treatment related toxicity prior to efficacy evaluation and 1 patient expired prior to efficacy evaluation. These two patients are not included in this outcome measure.

Outcome measures

Outcome measures
Measure	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation n=6 Participants Cisplatin 75 mg/m\^2 IV every 21 days for 4 cycles or Carboplatin AUC 6 IV every 21 days for 4 cycles. Radiation beginning cycle 2 day 1 daily for 5-6 weeks 45-50 Gy. Recommended mastectomy Recommended adjuvant chemotherapy -Doxorubicin 60 mg/m\^2 and cyclophosphamide 600 mg/m\^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m\^2 for 14 days for 4 cycles)
Response Rate as Measured by Number of Participants Who Achieved Complete Response (CR) or Partial Response (PR) Pathologic complete response	3 Participants
Response Rate as Measured by Number of Participants Who Achieved Complete Response (CR) or Partial Response (PR) Partial response	3 Participants

PRIMARY outcome

Timeframe: Prior to surgery (approximately 12-16 weeks from registration)

Population: The physician who was to perform the correlative laboratory work for the study left the university prior to performing the correlative work for this study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years from registration

Population: There are 8 participants not included in this outcome measure and the reasons are as follows: (1) removed from study due to treatment related toxicity prior to surgery, (1) expired prior to surgery, and (6) did not have progressive disease.

Progression = at least a 20% increase in the sum of the longest diameter of the target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, appearance of one or more new lesions, unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation n=2 Participants Cisplatin 75 mg/m\^2 IV every 21 days for 4 cycles or Carboplatin AUC 6 IV every 21 days for 4 cycles. Radiation beginning cycle 2 day 1 daily for 5-6 weeks 45-50 Gy. Recommended mastectomy Recommended adjuvant chemotherapy -Doxorubicin 60 mg/m\^2 and cyclophosphamide 600 mg/m\^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m\^2 for 14 days for 4 cycles)
Time to Disease Progression	6.5 months Interval 1.5 to 11.5

SECONDARY outcome

Timeframe: 30 days post surgery (approximately 16-20 weeks from registration)

Population: 1 patient was removed from study due to treatment related toxicity prior to surgery and 1 patient expired prior to surgery. These two patients are not included in this outcome measure.

Outcome measures

Outcome measures
Measure	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation n=6 Participants Cisplatin 75 mg/m\^2 IV every 21 days for 4 cycles or Carboplatin AUC 6 IV every 21 days for 4 cycles. Radiation beginning cycle 2 day 1 daily for 5-6 weeks 45-50 Gy. Recommended mastectomy Recommended adjuvant chemotherapy -Doxorubicin 60 mg/m\^2 and cyclophosphamide 600 mg/m\^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m\^2 for 14 days for 4 cycles)
Number of Participants With Surgical Complications	1 participant

SECONDARY outcome

Timeframe: Up to 15 months from registration

Population: The physician who was to perform the correlative laboratory work for the study left the university prior to performing the correlative work for this study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Median follow-up was 59.9 months

Population: 1 patient was removed from study due to treatment related toxicity prior to surgery and 1 patient expired prior to surgery. These 2 patients are not included in this outcome measure.

Outcome measures

Outcome measures
Measure	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation n=8 Participants Cisplatin 75 mg/m\^2 IV every 21 days for 4 cycles or Carboplatin AUC 6 IV every 21 days for 4 cycles. Radiation beginning cycle 2 day 1 daily for 5-6 weeks 45-50 Gy. Recommended mastectomy Recommended adjuvant chemotherapy -Doxorubicin 60 mg/m\^2 and cyclophosphamide 600 mg/m\^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m\^2 for 14 days for 4 cycles)
Overall Survival Rate	75 percentage of participants

SECONDARY outcome

Timeframe: 30 days post surgery (approximately 16-20 weeks after start of registration)

Outcome measures

Outcome measures
Measure	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation n=8 Participants Cisplatin 75 mg/m\^2 IV every 21 days for 4 cycles or Carboplatin AUC 6 IV every 21 days for 4 cycles. Radiation beginning cycle 2 day 1 daily for 5-6 weeks 45-50 Gy. Recommended mastectomy Recommended adjuvant chemotherapy -Doxorubicin 60 mg/m\^2 and cyclophosphamide 600 mg/m\^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m\^2 for 14 days for 4 cycles)
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Cerebrovascular accident	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Acute kidney injury	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Anemia	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Leukocytosis	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Cardiac arrest	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Pulseless electrical activity	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Sinus bradycardia	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Fever	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Wound infection	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Radiation recall reaction (dermatologic)	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Alanine aminotransferase increased	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Creatinine increased	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Lymphocyte count decreased	4 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Neutrophil count decreased	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Platelet count decreased	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Weight gain	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Hyponatremia	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Back pain	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Cellulitis	1 adverse event
Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events Hypertension	1 adverse event

Adverse Events

Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation n=8 participants at risk Cisplatin 75 mg/m\^2 IV every 21 days for 4 cycles or Carboplatin AUC 6 IV every 21 days for 4 cycles. Radiation beginning cycle 2 day 1 daily for 5-6 weeks 45-50 Gy. Recommended mastectomy Recommended adjuvant chemotherapy -Doxorubicin 60 mg/m\^2 and cyclophosphamide 600 mg/m\^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m\^2 for 14 days for 4 cycles)
Blood and lymphatic system disorders Anemia	25.0% 2/8
Metabolism and nutrition disorders Anorexia	12.5% 1/8
Nervous system disorders Ataxia	12.5% 1/8
Musculoskeletal and connective tissue disorders Back pain	12.5% 1/8
Infections and infestations Bacteremia	12.5% 1/8
Cardiac disorders Bradycardia	12.5% 1/8
Cardiac disorders Cardiac arrest	12.5% 1/8
Skin and subcutaneous tissue disorders Cellulitis	12.5% 1/8
Nervous system disorders Cerebral-vascular accident	12.5% 1/8
General disorders Chills	25.0% 2/8
Investigations Decreased lymphocytes	25.0% 2/8
Investigations Decreased platelets	12.5% 1/8
Nervous system disorders Dysarthia	12.5% 1/8
General disorders Fever	25.0% 2/8
Metabolism and nutrition disorders Hypercalcemia	12.5% 1/8
Metabolism and nutrition disorders Hyperglycemia	12.5% 1/8
Metabolism and nutrition disorders Hyperkalemia	12.5% 1/8
Vascular disorders Hypertension	12.5% 1/8
Metabolism and nutrition disorders Hypertriglyceridemia	12.5% 1/8
Metabolism and nutrition disorders Hypoalbuminemia	25.0% 2/8
Metabolism and nutrition disorders Hypocalcemia	12.5% 1/8
Metabolism and nutrition disorders Hypoglycemia	12.5% 1/8
Metabolism and nutrition disorders Hypomagnesemia	12.5% 1/8
Metabolism and nutrition disorders Hyponatremia	12.5% 1/8
Investigations Increased creatinine	25.0% 2/8
Investigations Increased international normalized ratio (INR)	12.5% 1/8
Blood and lymphatic system disorders Leukocytosis	12.5% 1/8
Gastrointestinal disorders Nausea	12.5% 1/8
Cardiac disorders Pulseless electrical activity	12.5% 1/8
Infections and infestations Urinary tract infection	12.5% 1/8
Gastrointestinal disorders Vomiting	25.0% 2/8
Renal and urinary disorders Acute renal injury	12.5% 1/8
Investigations Alkaline phosphatase increased	25.0% 2/8

Other adverse events

Other adverse events
Measure	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation n=8 participants at risk Cisplatin 75 mg/m\^2 IV every 21 days for 4 cycles or Carboplatin AUC 6 IV every 21 days for 4 cycles. Radiation beginning cycle 2 day 1 daily for 5-6 weeks 45-50 Gy. Recommended mastectomy Recommended adjuvant chemotherapy -Doxorubicin 60 mg/m\^2 and cyclophosphamide 600 mg/m\^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m\^2 for 14 days for 4 cycles)
Investigations Alanine aminotransferase increased	37.5% 3/8
Skin and subcutaneous tissue disorders Alopecia	25.0% 2/8
Blood and lymphatic system disorders Anemia	62.5% 5/8
Psychiatric disorders Anxiety	12.5% 1/8
Investigations Aspartate aminotransferase increased	37.5% 3/8
Skin and subcutaneous tissue disorders Body boils	12.5% 1/8
Skin and subcutaneous tissue disorders Body odor	12.5% 1/8
Musculoskeletal and connective tissue disorders Bone pain	12.5% 1/8
Infections and infestations Breast infection	12.5% 1/8
Reproductive system and breast disorders Breast pain	25.0% 2/8
Injury, poisoning and procedural complications Bruising	12.5% 1/8
Gastrointestinal disorders Constipation	37.5% 3/8
Respiratory, thoracic and mediastinal disorders Cough	25.0% 2/8
Metabolism and nutrition disorders Dehydration	12.5% 1/8
Psychiatric disorders Depression	12.5% 1/8
Gastrointestinal disorders Diarrhea	37.5% 3/8
Gastrointestinal disorders Dry mouth	12.5% 1/8
Gastrointestinal disorders Dyspepsia	12.5% 1/8
Gastrointestinal disorders Dysphagia	12.5% 1/8
Respiratory, thoracic and mediastinal disorders Dyspnea	25.0% 2/8
Ear and labyrinth disorders Ear clogging	12.5% 1/8
General disorders Edema - limbs	37.5% 3/8
General disorders Edema - trunk	25.0% 2/8
Skin and subcutaneous tissue disorders Erythema multiforme	12.5% 1/8
Injury, poisoning and procedural complications Fall	12.5% 1/8
General disorders Fatigue	62.5% 5/8
General disorders Fever	12.5% 1/8
Nervous system disorders Headache	25.0% 2/8
Ear and labyrinth disorders Hearing impaired	12.5% 1/8
Respiratory, thoracic and mediastinal disorders Hoarseness	12.5% 1/8
Vascular disorders Hot flashes	25.0% 2/8
Metabolism and nutrition disorders Hypercalcemia	12.5% 1/8
Metabolism and nutrition disorders Hyperglycemia	37.5% 3/8
Skin and subcutaneous tissue disorders Hyperhidrosis	12.5% 1/8
Metabolism and nutrition disorders Hypoalbuminemia	12.5% 1/8
Metabolism and nutrition disorders Hypocalcemia	12.5% 1/8
Metabolism and nutrition disorders Hypoglycemia	12.5% 1/8
Metabolism and nutrition disorders Hyponatremia	25.0% 2/8
Psychiatric disorders Insomnia	12.5% 1/8
Musculoskeletal and connective tissue disorders Joint range of motion decreased	12.5% 1/8
General disorders Leg cramping	12.5% 1/8
Vascular disorders Lymphedema	12.5% 1/8
Investigations Lymphocyte count decreased	75.0% 6/8
Nervous system disorders Memory impairment	12.5% 1/8
Reproductive system and breast disorders Menorrhagia	12.5% 1/8
Skin and subcutaneous tissue disorders Nail discoloration	12.5% 1/8
Gastrointestinal disorders Nausea	50.0% 4/8
Investigations Neutrophil count decreased	50.0% 4/8
Skin and subcutaneous tissue disorders Pain of skin	12.5% 1/8
Nervous system disorders Peripheral sensory neuropathy	62.5% 5/8
Infections and infestations Pharyngitis	12.5% 1/8
Skin and subcutaneous tissue disorders Photosensitivity	12.5% 1/8
Investigations Platelet count decreased	12.5% 1/8
Skin and subcutaneous tissue disorders Pruritus	12.5% 1/8
Injury, poisoning and procedural complications Radiation recall reaction (dermatologic)	50.0% 4/8
Skin and subcutaneous tissue disorders Rash acneiform	37.5% 3/8
Injury, poisoning and procedural complications Seroma	12.5% 1/8
Respiratory, thoracic and mediastinal disorders Sinus disorder	12.5% 1/8
Skin and subcutaneous tissue disorders Skin hypopigmentation	12.5% 1/8
Respiratory, thoracic and mediastinal disorders Sore throat	12.5% 1/8
Skin and subcutaneous tissue disorders Sweating	12.5% 1/8
Ear and labyrinth disorders Tinnitus	12.5% 1/8
Infections and infestations Upper respiratory infection	25.0% 2/8
Gastrointestinal disorders Vomiting	25.0% 2/8
Eye disorders Watering eyes	12.5% 1/8
Investigations Weight gain	12.5% 1/8
Investigations White blood cell decreased	50.0% 4/8
Infections and infestations Wound infection	12.5% 1/8

Additional Information

Rebecca Aft, M.D., Ph.D.

Washington University School of Medicine

Phone: 314-747-0063

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place