Trial Outcomes & Findings for NOV-002, Doxorubicin, Cyclophosphamide, and Docetaxel in Women With Newly Diagnosed Stage II or IIIC Breast Cancer (NCT NCT00499122)

Last Updated: 2018-01-02

Results Overview

The primary objective of this study is to define the rate of pathologic complete response rate (pCR) in the affected breast after the preoperative administration of NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with stage IIB-IIIC breast cancer. Pathologic complete response (pCR) is defined according to Hankoop et al \[41\] as either: the absence of any histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast or the presence of invasive tumor equal to or less than 10mm after preoperative treatment, determined at definitive breast surgery.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

41 participants

Primary outcome timeframe

About 7 months

Results posted on

2018-01-02

Participant Flow

Participant milestones

Participant milestones
Measure	NOV-002 and Chemotherapy * NOV-002: * Cycle 1, Day -1 only: 60 mg intravenously (IV) x 2, 3 hours (+/- 30 minutes) apart * Cycles 1 - 8, Day 1: 60 mg IV, 1 hour (+/- 30 minutes) prior to chemotherapy administration * Cycle 1 - 8, Days 2 - 21: 60 mg subcutaneous injections * Cyclophosphamide: 600 mg/m2 IV, Cycles 1 - 4, Day 1 * Doxorubicin: 60 mg/m2 IV, Cycles 1 - 4, Day 1 * Docetaxel: 100 mg/m2 IV, Cycles 5 - 8, Day 1
Overall Study STARTED	41
Overall Study COMPLETED	39
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	NOV-002 and Chemotherapy * NOV-002: * Cycle 1, Day -1 only: 60 mg intravenously (IV) x 2, 3 hours (+/- 30 minutes) apart * Cycles 1 - 8, Day 1: 60 mg IV, 1 hour (+/- 30 minutes) prior to chemotherapy administration * Cycle 1 - 8, Days 2 - 21: 60 mg subcutaneous injections * Cyclophosphamide: 600 mg/m2 IV, Cycles 1 - 4, Day 1 * Doxorubicin: 60 mg/m2 IV, Cycles 1 - 4, Day 1 * Docetaxel: 100 mg/m2 IV, Cycles 5 - 8, Day 1
Overall Study Withdrawal by Subject	2

Baseline Characteristics

NOV-002, Doxorubicin, Cyclophosphamide, and Docetaxel in Women With Newly Diagnosed Stage II or IIIC Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NOV-002 and Chemotherapy n=41 Participants * NOV-002: * Cycle 1, Day -1 only: 60 mg intravenously (IV) x 2, 3 hours (+/- 30 minutes) apart * Cycles 1 - 8, Day 1: 60 mg IV, 1 hour (+/- 30 minutes) prior to chemotherapy administration * Cycle 1 - 8, Days 2 - 21: 60 mg subcutaneous injections * Cyclophosphamide: 600 mg/m2 IV, Cycles 1 - 4, Day 1 * Doxorubicin: 60 mg/m2 IV, Cycles 1 - 4, Day 1 * Docetaxel: 100 mg/m2 IV, Cycles 5 - 8, Day 1
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 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	13 Participants n=5 Participants
Race (NIH/OMB) White	26 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

PRIMARY outcome

Timeframe: About 7 months

Population: Assessable tumors from study participants who had received at least one cycle of protocol therapy.

Outcome measures

Outcome measures
Measure	NOV-002 and Chemotherapy n=40 Tumors * NOV-002: * Cycle 1, Day -1 only: 60 mg intravenously (IV) x 2, 3 hours (+/- 30 minutes) apart * Cycles 1 - 8, Day 1: 60 mg IV, 1 hour (+/- 30 minutes) prior to chemotherapy administration * Cycle 1 - 8, Days 2 - 21: 60 mg subcutaneous injections * Cyclophosphamide: 600 mg/m2 IV, Cycles 1 - 4, Day 1 * Doxorubicin: 60 mg/m2 IV, Cycles 1 - 4, Day 1 * Docetaxel: 100 mg/m2 IV, Cycles 5 - 8, Day 1
Rate of Pathologic Complete Response in the Affected Breast After Protocol Therapy	39 percentage of tumors Interval 25.0 to 45.0

SECONDARY outcome

Timeframe: Up to 30 days Post-Last Dose of Protocol Therapy, About 7 months

Definition of the safety profiles of protocol therapy in study participants as shown by the number of study participants experiencing adverse events or other toxicity.

Outcome measures

Outcome measures
Measure	NOV-002 and Chemotherapy n=41 Participants * NOV-002: * Cycle 1, Day -1 only: 60 mg intravenously (IV) x 2, 3 hours (+/- 30 minutes) apart * Cycles 1 - 8, Day 1: 60 mg IV, 1 hour (+/- 30 minutes) prior to chemotherapy administration * Cycle 1 - 8, Days 2 - 21: 60 mg subcutaneous injections * Cyclophosphamide: 600 mg/m2 IV, Cycles 1 - 4, Day 1 * Doxorubicin: 60 mg/m2 IV, Cycles 1 - 4, Day 1 * Docetaxel: 100 mg/m2 IV, Cycles 5 - 8, Day 1
Definition of the Safety Profiles of Protocol Therapy	41 participants

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycles 1 through 8, about 7 months

Population: Study participants who were evaluable for pathologic response.

The investigators hypothesized that patients with favorable responses, i.e. pCR, are more likely to have significantly lower levels of MDSCs than non-responders. MDSC levels will be measured at baseline and on day 1 of each treatment cycle, cycles 1 through 8.

Outcome measures

Outcome measures
Measure	NOV-002 and Chemotherapy n=39 Participants * NOV-002: * Cycle 1, Day -1 only: 60 mg intravenously (IV) x 2, 3 hours (+/- 30 minutes) apart * Cycles 1 - 8, Day 1: 60 mg IV, 1 hour (+/- 30 minutes) prior to chemotherapy administration * Cycle 1 - 8, Days 2 - 21: 60 mg subcutaneous injections * Cyclophosphamide: 600 mg/m2 IV, Cycles 1 - 4, Day 1 * Doxorubicin: 60 mg/m2 IV, Cycles 1 - 4, Day 1 * Docetaxel: 100 mg/m2 IV, Cycles 5 - 8, Day 1
Correlation Between Myeloid Derived Suppressor Cell (MDSC) Levels and Pathologic Complete Response (pCR) and Non-Responders Baseline, non-pCR	257.4 MDSC/uL Standard Error 0.001
Correlation Between Myeloid Derived Suppressor Cell (MDSC) Levels and Pathologic Complete Response (pCR) and Non-Responders Baseline, pCR	124.3 MDSC/uL Standard Error 0.001
Correlation Between Myeloid Derived Suppressor Cell (MDSC) Levels and Pathologic Complete Response (pCR) and Non-Responders Cycles 2-4 Day 1, non-pCR	534.2 MDSC/uL Standard Error 0.02
Correlation Between Myeloid Derived Suppressor Cell (MDSC) Levels and Pathologic Complete Response (pCR) and Non-Responders Cycles 2-4 Day 1, pCR	207.8 MDSC/uL Standard Error 0.02
Correlation Between Myeloid Derived Suppressor Cell (MDSC) Levels and Pathologic Complete Response (pCR) and Non-Responders Cycles 5-8 Day 1, non-pCR	363.7 MDSC/uL Standard Error 0.006
Correlation Between Myeloid Derived Suppressor Cell (MDSC) Levels and Pathologic Complete Response (pCR) and Non-Responders Cycles 5-8 Day 1, pCR	171.5 MDSC/uL Standard Error 0.006

Adverse Events

NOV-002 and Chemotherapy

Serious events: 27 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	NOV-002 and Chemotherapy n=41 participants at risk * NOV-002: * Cycle 1, Day -1 only: 60 mg intravenously (IV) x 2, 3 hours (+/- 30 minutes) apart * Cycles 1 - 8, Day 1: 60 mg IV, 1 hour (+/- 30 minutes) prior to chemotherapy administration * Cycle 1 - 8, Days 2 - 21: 60 mg subcutaneous injections * Cyclophosphamide: 600 mg/m2 IV, Cycles 1 - 4, Day 1 * Doxorubicin: 60 mg/m2 IV, Cycles 1 - 4, Day 1 * Docetaxel: 100 mg/m2 IV, Cycles 5 - 8, Day 1
Blood and lymphatic system disorders Febrile Neutropenia	9.8% 4/41
Nervous system disorders Sensory Neuropathy	9.8% 4/41
Gastrointestinal disorders Abdominal Pain	4.9% 2/41
General disorders Fatigue	4.9% 2/41
General disorders Headache	2.4% 1/41
Musculoskeletal and connective tissue disorders Cellulitis	2.4% 1/41
Blood and lymphatic system disorders Neutropenia	2.4% 1/41
Musculoskeletal and connective tissue disorders Muscular Weakness	2.4% 1/41
Blood and lymphatic system disorders Deep Vein Thrombosis	2.4% 1/41
Cardiac disorders Femoral Artery occlusion	2.4% 1/41
Gastrointestinal disorders Constipation	2.4% 1/41
Musculoskeletal and connective tissue disorders Palmar-plantar erythroysaesthesia	14.6% 6/41
Blood and lymphatic system disorders Pulmonary embolism	2.4% 1/41
General disorders Nausea	2.4% 1/41

Other adverse events

Other adverse events
Measure	NOV-002 and Chemotherapy n=41 participants at risk * NOV-002: * Cycle 1, Day -1 only: 60 mg intravenously (IV) x 2, 3 hours (+/- 30 minutes) apart * Cycles 1 - 8, Day 1: 60 mg IV, 1 hour (+/- 30 minutes) prior to chemotherapy administration * Cycle 1 - 8, Days 2 - 21: 60 mg subcutaneous injections * Cyclophosphamide: 600 mg/m2 IV, Cycles 1 - 4, Day 1 * Doxorubicin: 60 mg/m2 IV, Cycles 1 - 4, Day 1 * Docetaxel: 100 mg/m2 IV, Cycles 5 - 8, Day 1
General disorders Nausea	75.6% 31/41
General disorders Fatigue	70.7% 29/41
Gastrointestinal disorders Consitpation	39.0% 16/41
Gastrointestinal disorders Vomiting	36.6% 15/41
Nervous system disorders Sensory Neuropathy	26.8% 11/41
Gastrointestinal disorders Diarrhea	26.8% 11/41

Additional Information

Alberto Montero MD

UM/Sylvester Comprehensive Cancer Center

Phone: 305-243-3771

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place