NCT01881230: tnAcity

Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

Completed Phase 2, PHASE3 Results posted Last updated 21 February 2019

What this trial tests

Phase 2, PHASE3 trial testing nab-Paclitaxel in Breast Tumor in 191 participants. Completed in 28 October 2016.

Timeline

26 September 2013

Primary endpoint
28 October 2016

28 October 2016

Quick facts

Lead sponsor	Celgene
Phase	Phase 2, PHASE3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	191
Start date	26 September 2013
Primary completion	28 October 2016
Estimated completion	28 October 2016
Sites	140 locations across France, Italy, Greece, Austria, United Kingdom, Germany, Canada, Australia

Drugs / interventions tested

• nab-Paclitaxel (nab-paclitaxel) — full drug profile →
• Carboplatin (Carboplatin) — full drug profile →
• Gemcitabine (gemcitabine) — full drug profile →

Conditions studied

• Breast Tumor — all drugs for Breast Tumor →
• Breast Cancer — all drugs for Breast Cancer →
• Cancer of the Breast — all drugs for Cancer of the Breast →
• Estrogen Receptor- Negative Breast Cancer — all drugs for Estrogen Receptor- Negative Breast Cancer →

Sponsor

Celgene — full company profile →

Who can join

18 and older, female only, with Breast Tumor or Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Kaplan-Meier Estimates of Progression-Free Survival (PFS) Based on Investigator Assessment. Primary · From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

PFS was defined as the time from the date of randomization to the date of disease progression or death from any cause on or prior to the data cutoff date for the statistical analysis, whichever occurred earlier. Tumor responses were assessed every 6 weeks using, Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and defined as: Complete response (CR) is the disappearance of all target lesions; Partial response (PR) occurs when at least a 30% decrease in the sum of diameters of target lesions from baseline; Stable disease is neither sufficient shrinkage to qualify for a PR nor sufficient

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	5.5	4.1 – 7.0
Arm B: Nab-Paclitaxel + Carboplatin	8.3	5.7 – 10.6
Arm C: Gemcitabine + Carboplatin	6.0	4.7 – 7.2

Percentage of Participants With an Objective Complete or Partial Overall Response by Investigator Assessment. Secondary · Disease response was assessed every 6 weeks; from date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

Percentage of participants with an Objective Complete or Partial Overall Response according to RECIST 1.1 and defined as: Complete response-disappearance of all target lesions; partial response at least a 30% decrease in the sum of diameters of target lesions from baseline; stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD)• Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	39.3	27.1 – 52.7
Arm B: Nab-Paclitaxel + Carboplatin	73.4	60.9 – 83.7
Arm C: Gemcitabine + Carboplatin	43.9	31.7 – 56.7

Percentage of Participants Who Initiated Cycle 6 Receiving Doublet Combination Therapy Secondary · Cycle 6

The percentage of participants who initiated Cycle 6 receiving doublet combination therapy regardless of the need for dose modifications.

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	55.7	42.5 – 68.5
Arm B: Nab-Paclitaxel + Carboplatin	64.1	51.1 – 75.7
Arm C: Gemcitabine + Carboplatin	50.0	37.4 – 62.6

Kaplan-Meier Estimates of Overall Survival Secondary · From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

Overall survival was defined as the time from the date of randomization to the date of death (from any cause).

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	12.1	9.4 – 15.9
Arm B: Nab-Paclitaxel + Carboplatin	16.8	11.3 – 20.6
Arm C: Gemcitabine + Carboplatin	12.6	10.1 – 16.6

Number of Participants With Treatment Emergent Adverse Events (TEAEs) Secondary · From randomization through to 28 days after the last dose of IP; up to data cut off date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C

Treatment-emergent adverse events (TEAEs) were defined as any AEs that began or worsened with the onset date on or after the date of the first dose of IP through 28 days after the last dose. A serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was graded based on the participant's symptoms according to the Common Terminology Criteria for Ad

Any TEAE

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	60
Arm B: Nab-Paclitaxel + Carboplatin	63
Arm C: Gemcitabine + Carboplatin	64

Any Grade 3 or Higher TEAE

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	46
Arm B: Nab-Paclitaxel + Carboplatin	51
Arm C: Gemcitabine + Carboplatin	54

Treatment-related TEAE

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	59
Arm B: Nab-Paclitaxel + Carboplatin	62
Arm C: Gemcitabine + Carboplatin	60

Treatment-related, Grade 3 or Higher TEAE

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	35
Arm B: Nab-Paclitaxel + Carboplatin	43
Arm C: Gemcitabine + Carboplatin	46

Serious TEAE

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	22
Arm B: Nab-Paclitaxel + Carboplatin	20
Arm C: Gemcitabine + Carboplatin	25

Treatment-related Serious TEAE

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	10
Arm B: Nab-Paclitaxel + Carboplatin	9
Arm C: Gemcitabine + Carboplatin	13

TEAE Leading to Discontinuation (D/C) of IP

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	16
Arm B: Nab-Paclitaxel + Carboplatin	29
Arm C: Gemcitabine + Carboplatin	15

Treatment Related (TR) TEAE Leading to D/C of IP

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	12
Arm B: Nab-Paclitaxel + Carboplatin	27
Arm C: Gemcitabine + Carboplatin	12

Percentage of Participants Experiencing Dose Modifications (Reductions and Interruptions) Secondary · From randomization through to 28 days after the last dose of IP; up to data-cut off of date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C

The number of participants with dose modifications occurring during the treatment period. Dose reductions and interruptions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.

≥ one DR for both IPs

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	33.3
Arm B: Nab-Paclitaxel + Carboplatin	46.9
Arm C: Gemcitabine + Carboplatin	51.6

≥ one DI for both IPs

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	38.3
Arm B: Nab-Paclitaxel + Carboplatin	70.3
Arm C: Gemcitabine + Carboplatin	73.4

≥ one dose missed for both IPs

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	48.3
Arm B: Nab-Paclitaxel + Carboplatin	45.3
Arm C: Gemcitabine + Carboplatin	56.3

Percentage of Participants Who Discontinued From All Study Treatment Due to TEAEs Secondary · From randomization through to 28 days after the last dose of IP; up to data-cut off of date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C

Treatment-emergent adverse events (TEAEs) were defined as any AEs that begin or worsen with an onset date on or after the date of the first dose of IP through 28 days after the last dose.

Group	Value	95% CI
Arm A: Nab-Paclitaxel + Gemcitabine	21.7	12.1 – 34.2
Arm B: Nab-Paclitaxel + Carboplatin	26.6	16.3 – 39.1
Arm C: Gemcitabine + Carboplatin	21.9	12.5 – 34.0

Adverse events — posted to ClinicalTrials.gov

Time frame: From randomization through to 28 days after the last dose of IP; up to the data cut-off date of 16 December 2016; AEs collected and monitored for 39 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A: Nab-Paclitaxel + Gemcitabine

Serious: 22/60 (37%)

Deaths: —

Arm B: Nab-Paclitaxel + Carboplatin

Serious: 20/64 (31%)

Deaths: —

Arm C: Gemcitabine + Carboplatin

Serious: 25/64 (39%)

Deaths: —

Serious adverse events (80 terms)

Reaction	System	Arm A: Nab-Paclitaxel + Ge…	Arm B: Nab-Paclitaxel + Ca…	Arm C: Gemcitabine + Carbo…
Anaemia	Blood and lymphatic system disorders	—	—	—
Pyrexia	General disorders	—	—	—
Pneumonia	Infections and infestations	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Non-cardiac chest pain	General disorders	—	—	—
Respiratory tract infection	Infections and infestations	—	—	—
Sepsis	Infections and infestations	—	—	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—
Pancytopenia	Blood and lymphatic system disorders	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—
Cardiac failure	Cardiac disorders	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—
Palpitations	Cardiac disorders	—	—	—
Pericardial effusion	Cardiac disorders	—	—	—
Ascites	Gastrointestinal disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Diverticular perforation	Gastrointestinal disorders	—	—	—
Haematemesis	Gastrointestinal disorders	—	—	—

Other adverse events (88 terms — click to expand)

Reaction	System	Arm A: Nab-Paclitaxel + Ge…	Arm B: Nab-Paclitaxel + Ca…	Arm C: Gemcitabine + Carbo…
Neutropenia	Blood and lymphatic system disorders	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Fatigue	General disorders	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Oedema peripheral	General disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Asthenia	General disorders	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Pyrexia	General disorders	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Dizziness	Nervous system disorders	—	—	—
Neuropathy peripheral	Nervous system disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Drug hypersensitivity	Immune system disorders	—	—	—
Dysgeusia	Nervous system disorders	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—
Weight decreased	Investigations	—	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—
Hypertension	Vascular disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Paraesthesia	Nervous system disorders	—	—	—

Most-reported serious reactions: Anaemia, Pyrexia, Pneumonia, Febrile neutropenia, Neutropenia, Thrombocytopenia, Nausea, Non-cardiac chest pain.

Data from ClinicalTrials.gov NCT01881230 adverse events section.

Sponsor's own description

The purpose of this study is to compare the safety and efficacy of nab-paclitaxel in combination with either gemcitabine or carboplatin to the combination of gemcitabine and carboplatin as first line treatment in female subjects with triple negative metastatic breast cancer (TNMBC) or metastatic triple negative breast cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer-How We Can Rise to the Challenge.
   Nedeljković M, Damjanović A. · · 2019 · cited 576× · PMID 31443516 · DOI 10.3390/cells8090957
2. Clinical Translation of Nanomedicine.
   Min Y, Caster JM, Eblan MJ, Wang AZ. · · 2015 · cited 495× · PMID 26088284 · DOI 10.1021/acs.chemrev.5b00116
3. Albumin-bound paclitaxel in solid tumors: clinical development and future directions.
   Kundranda MN, Niu J. · · 2015 · cited 162× · PMID 26244011 · DOI 10.2147/dddt.s88023
4. nab-Paclitaxel plus carboplatin or gemcitabine versus gemcitabine plus carboplatin as first-line treatment of patients with triple-negative metastatic breast cancer: results from the tnAcity trial.
   Yardley DA, Coleman R, Conte P, Cortes J, et al · · 2018 · cited 104× · PMID 29878040 · DOI 10.1093/annonc/mdy201
5. The role of taxanes in triple-negative breast cancer: literature review.
   Mustacchi G, De Laurentiis M. · · 2015 · cited 102× · PMID 26273192 · DOI 10.2147/dddt.s86105
6. Therapies for triple negative breast cancer.
   Andreopoulou E, Schweber SJ, Sparano JA, McDaid HM. · · 2015 · cited 77× · PMID 25881743 · DOI 10.1517/14656566.2015.1032246
7. TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy.
   Singh DD, Yadav DK. · · 2021 · cited 76× · PMID 34440080 · DOI 10.3390/biomedicines9080876
8. Potentiation of Carboplatin-Mediated DNA Damage by the Mdm2 Modulator Nutlin-3a in a Humanized Orthotopic Breast-to-Lung Metastatic Model.
   Tonsing-Carter E, Bailey BJ, Saadatzadeh MR, Ding J, et al · · 2015 · cited 36× · PMID 26494859 · DOI 10.1158/1535-7163.mct-15-0237