Trial Outcomes & Findings for RAD001 Plus Carboplatin in Breast Cancer Patients (NCT NCT01127763)

Last Updated: 2014-04-09

Results Overview

Clinical benefit rate is defined as the number of patients with complete response (CR), partial response (PR), or stable disease (SD) that lasts at least 6 months. Response was assessed every 2 cycles of treatment (6 weeks) by computed tomography (CT), CT/positron emission tomography (PET), or magnetic resonance imaging (MRI). Overall response evaluation is based on Response Evaluation Criteria In Solid Tumors 1.0 (RECIST 1.0). Per RECIST 1.0 for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

up to 1 year

Results posted on

2014-04-09

Participant Flow

From June 2010 to July 2012, 25 patients were enrolled from New York University Medical center and its affiliated hospitals.

Participant milestones

Participant milestones
Measure	RAD001+Carboplatin Carboplatin (starting dose was initially AUC 6, later decreased to AUC 5, then AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day until disease progression or unacceptable toxicity.
Overall Study STARTED	25
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	RAD001+Carboplatin Carboplatin (starting dose was initially AUC 6, later decreased to AUC 5, then AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day until disease progression or unacceptable toxicity.
Overall Study Adverse Event	2
Overall Study Withdrawal by Subject	1
Overall Study Physician Decision	2

Baseline Characteristics

RAD001 Plus Carboplatin in Breast Cancer Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RAD001+Carboplatin n=25 Participants Carboplatin (starting dose was initially AUC 6, later decreased to AUC 5, then AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day until disease progression or unacceptable toxicity.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants
Age, Continuous	58 years n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants
Number of prior chemotherapy regimens	1 chemotherapy regimens n=5 Participants

PRIMARY outcome

Timeframe: up to 1 year

Population: Any patient with at least one dose of treatment.

Outcome measures

Outcome measures
Measure	RAD001+Carboplatin n=25 Participants Carboplatin (starting dose was initially AUC 6, later decreased to AUC 5, then AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day until disease progression or unacceptable toxicity. RAD001 Carboplatin	RAD001+Carboplatin (AUC 4) Carboplatin (starting dose of AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day.	RAD001+Carboplatin (All Patients) Carboplatin every 3 weeks as IV infusion and RAD001 as 5 mg pill each day.
Clinical Benefit Rate (Complete Response, Partial Response, and Stable Disease That Lasts More Than 6 Months)	36 percentage of patients Interval 21.0 to 57.0	—	—

PRIMARY outcome

Timeframe: treatment period (up to 1 year) plus 30 days off treatment

Population: any patient who received at least 1 dose of protocol treatment.

Reported as percentage of patients who experienced grade 3 and higher hematological adverse events (AEs) related to the study drugs.

Outcome measures

Outcome measures
Measure	RAD001+Carboplatin n=7 Participants Carboplatin (starting dose was initially AUC 6, later decreased to AUC 5, then AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day until disease progression or unacceptable toxicity. RAD001 Carboplatin	RAD001+Carboplatin (AUC 4) n=18 Participants Carboplatin (starting dose of AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day.	RAD001+Carboplatin (All Patients) n=25 Participants Carboplatin every 3 weeks as IV infusion and RAD001 as 5 mg pill each day.
Toxicity Profile-Hematological Anemia	0 percentage of patients	5 percentage of patients	4 percentage of patients
Toxicity Profile-Hematological Thrombocytopenia	71 percentage of patients	11 percentage of patients	28 percentage of patients
Toxicity Profile-Hematological Leukopenia	14 percentage of patients	0 percentage of patients	4 percentage of patients
Toxicity Profile-Hematological Neutropenia	29 percentage of patients	5 percentage of patients	12 percentage of patients

PRIMARY outcome

Timeframe: treatment period (up to 1 year) plus 30 days off treatment

Population: any patient who received at least 1 dose of protocol treatment.

Reported as percentage of patients who experienced grade 3 and higher non-hematological AEs related to the study drugs.

Outcome measures

Outcome measures
Measure	RAD001+Carboplatin n=25 Participants Carboplatin (starting dose was initially AUC 6, later decreased to AUC 5, then AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day until disease progression or unacceptable toxicity. RAD001 Carboplatin	RAD001+Carboplatin (AUC 4) Carboplatin (starting dose of AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day.	RAD001+Carboplatin (All Patients) Carboplatin every 3 weeks as IV infusion and RAD001 as 5 mg pill each day.
Toxicity Profile-Non Hematological Nausea	4 percentage of patients	—	—
Toxicity Profile-Non Hematological Vomiting	4 percentage of patients	—	—
Toxicity Profile-Non Hematological Dehydration	4 percentage of patients	—	—
Toxicity Profile-Non Hematological Mucositis	4 percentage of patients	—	—
Toxicity Profile-Non Hematological Hypersensitivity	4 percentage of patients	—	—

SECONDARY outcome

Timeframe: up to 1 year

Population: Any patient with at least one dose of treatment.

Progression-free survival time is defined as the time from first day of treatment to the first date of disease progression or death as a result of any cause. Progression was assessed every 2 cycles of treatment (6 weeks) by CT, CT/PET, or MRI. Progression is defined using RECIST 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	RAD001+Carboplatin n=25 Participants Carboplatin (starting dose was initially AUC 6, later decreased to AUC 5, then AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day until disease progression or unacceptable toxicity. RAD001 Carboplatin	RAD001+Carboplatin (AUC 4) Carboplatin (starting dose of AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day.	RAD001+Carboplatin (All Patients) Carboplatin every 3 weeks as IV infusion and RAD001 as 5 mg pill each day.
Median Progression-free Survival Time	3 months Interval 2.0 to 5.0	—	—

Adverse Events

RAD001+Carboplatin

Serious events: 5 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	RAD001+Carboplatin n=25 participants at risk Carboplatin (starting dose was initially AUC 6, later decreased to AUC 5, then AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day until disease progression or unacceptable toxicity.
Cardiac disorders Hypertension	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Gastrointestinal disorders Dehydration	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Infections and infestations Infection With Normal Anc Or Grade 1 Or 2 Neutrophils	8.0% 2/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Nervous system disorders Pain	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Respiratory, thoracic and mediastinal disorders Dyspnea (Shortness Of Breath)	8.0% 2/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.

Other adverse events

Other adverse events
Measure	RAD001+Carboplatin n=25 participants at risk Carboplatin (starting dose was initially AUC 6, later decreased to AUC 5, then AUC 4) every 3 weeks as IV infusion and RAD001 as 5 mg pill each day until disease progression or unacceptable toxicity.
Skin and subcutaneous tissue disorders Pruritus/Itching	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Skin and subcutaneous tissue disorders Rash/Desquamation	16.0% 4/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Skin and subcutaneous tissue disorders Rash: Acne/Acneiform	16.0% 4/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Endocrine disorders Hot Flashes/Flushes	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Gastrointestinal disorders Anorexia	12.0% 3/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Gastrointestinal disorders Constipation	24.0% 6/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Gastrointestinal disorders Diarrhea	8.0% 2/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Gastrointestinal disorders Dry Mouth/Salivary Gland (Xerostomia)	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Gastrointestinal disorders Mucositis/Stomatitis (Functional/Symptomatic)	8.0% 2/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Gastrointestinal disorders Nausea	44.0% 11/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Respiratory, thoracic and mediastinal disorders Hemorrhage, Pulmonary/Upper Respiratory	12.0% 3/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Infections and infestations Infection With Normal Anc Or Grade 1 Or 2 Neutrophils	8.0% 2/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Blood and lymphatic system disorders Dermal Change Lymphedema, Phlebolymphedema	8.0% 2/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Gastrointestinal disorders Taste Alteration (Dysgeusia)	8.0% 2/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Gastrointestinal disorders Vomiting	28.0% 7/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Immune system disorders Allergic Reaction/Hypersensitivity (Including Drug Fever)	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Blood and lymphatic system disorders Hemolysis (E.G., Immune Hemolytic Anemia, Drug-Related Hemolysis)	36.0% 9/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Investigations Leukocytes (Total Wbc)	16.0% 4/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Investigations Neutrophils/Granulocytes (Anc/Agc)	44.0% 11/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Investigations Platelets	64.0% 16/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Investigations Inr (International Normalized Ratio Of Prothrombin Time)	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
General disorders Fatigue (Asthenia, Lethargy, Malaise)	44.0% 11/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
General disorders Fever (In The Absence Of Neutropenia, Where Neutropenia Is Defined As Anc <1.0 X 10e9/L)	12.0% 3/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Psychiatric disorders Insomnia	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Injury, poisoning and procedural complications Bruising (In Absence Of Grade 3 Or 4 Thrombocytopenia)	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Skin and subcutaneous tissue disorders Dermatology/Skin - Other (Specify, skin nodules	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Vascular disorders Flushing	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Blood and lymphatic system disorders Edema: Head And Neck	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Blood and lymphatic system disorders Edema: Limb	16.0% 4/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Metabolism and nutrition disorders Alkaline Phosphatase	12.0% 3/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Metabolism and nutrition disorders Alt, Sgpt (Serum Glutamic Pyruvic Transaminase)	12.0% 3/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Metabolism and nutrition disorders Ast, Sgot(Serum Glutamic Oxaloacetic Transaminase)	8.0% 2/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Investigations Cholesterol, Serum-High (Hypercholestremia)	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Metabolism and nutrition disorders Proteinuria	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Musculoskeletal and connective tissue disorders Extremity-Lower (Gait/Walking)	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Musculoskeletal and connective tissue disorders Muscle Weakness, Generalized Or Specific Area (Not Due To Neuropathy)	8.0% 2/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Nervous system disorders Dizziness	16.0% 4/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Nervous system disorders Mood Alteration	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Nervous system disorders Neuropathy: Sensory	12.0% 3/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Eye disorders Dry Eye Syndrome	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Injury, poisoning and procedural complications Pain - Other (Specify, incisional pain)	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Respiratory, thoracic and mediastinal disorders Cough	8.0% 2/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Respiratory, thoracic and mediastinal disorders Dyspnea (Shortness Of Breath)	12.0% 3/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Respiratory, thoracic and mediastinal disorders Nasal Cavity/Paranasal Sinus Reactions	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Respiratory, thoracic and mediastinal disorders Voice Changes/Dysarthria (E.G., Hoarseness, Loss Or Alteration In Voice, Laryngitis)	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Reproductive system and breast disorders Vaginal Discharge (Non-Infectious)	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Musculoskeletal and connective tissue disorders Pain_extremity-limb	12.0% 3/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Musculoskeletal and connective tissue disorders Pain_joint	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Musculoskeletal and connective tissue disorders Pain_back	16.0% 4/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Nervous system disorders Pain_headache	16.0% 4/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Reproductive system and breast disorders Pain_breast	8.0% 2/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Gastrointestinal disorders Pain_stomach	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.
Musculoskeletal and connective tissue disorders Pain_bone	4.0% 1/25 • AEs were assessed during the treatment and 30 days from the last day of treatment. All AEs are reported here regardless of attribution.

Additional Information

Amy Tiersten, MD

Mt Sinai School of Medicine

Phone: 212-249-3300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place