Trial Outcomes & Findings for Carboplatin, Paclitaxel, and Everolimus in Treating Patients With Previously Untreated Cancer of Unknown Primary (NCT NCT00936702)
NCT ID: NCT00936702
Last Updated: 2017-03-21
Results Overview
Confirmed tumor response was defined to be either a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: * Complete Response (CR): disappearance of all target lesions; * Partial Response (PR) 30% decrease in sum of longest diameter of target lesions;
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
46 participants
Primary outcome timeframe
First 6 Cycles of treatment (an average of 6 months)
Results posted on
2017-03-21
Participant Flow
Forty-six participants with centrally confirmed cancer of unknown primary site were enrolled between October 2009 and October 2012. The trial was closed before the target sample size of 50 was reached, because a sufficient number of confirmed responses had occurred to meet the primary endpoint.
Participant milestones
| Measure |
Treatment (Carboplatin, Paclitaxel, and Everolimus)
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
|
|---|---|
|
Overall Study
STARTED
|
46
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
46
|
Reasons for withdrawal
| Measure |
Treatment (Carboplatin, Paclitaxel, and Everolimus)
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
|
|---|---|
|
Overall Study
Disease progression
|
34
|
|
Overall Study
Adverse Event
|
8
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Alternative Treatment
|
1
|
|
Overall Study
Other
|
1
|
Baseline Characteristics
Carboplatin, Paclitaxel, and Everolimus in Treating Patients With Previously Untreated Cancer of Unknown Primary
Baseline characteristics by cohort
| Measure |
Treatment (Carboplatin, Paclitaxel, and Everolimus)
n=46 Participants
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
|
|---|---|
|
Age, Continuous
|
61 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0=Asymptomatic and fully active
|
25 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1=Symptomatic and fully ambulatory
|
15 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
2=Symptomatic and ambulatory
|
6 Participants
n=5 Participants
|
|
Histologic diagnosis
Adenocarcinoma
|
36 Participants
n=5 Participants
|
|
Histologic diagnosis
Poorly differentiated nonsmall-cell carcinoma
|
5 Participants
n=5 Participants
|
|
Histologic diagnosis
Poorly differentiated squamous carcinoma
|
1 Participants
n=5 Participants
|
|
Histologic diagnosis
Other
|
4 Participants
n=5 Participants
|
|
Histologic grade
Well
|
1 Participants
n=5 Participants
|
|
Histologic grade
Moderate
|
8 Participants
n=5 Participants
|
|
Histologic grade
Poor
|
28 Participants
n=5 Participants
|
|
Histologic grade
Undifferentiated, anaplastic
|
8 Participants
n=5 Participants
|
|
Histologic grade
Not Available
|
1 Participants
n=5 Participants
|
|
Predominant location of disease
Liver
|
18 Participants
n=5 Participants
|
|
Predominant location of disease
Lung
|
10 Participants
n=5 Participants
|
|
Predominant location of disease
Soft tissue
|
9 Participants
n=5 Participants
|
|
Predominant location of disease
Bone
|
3 Participants
n=5 Participants
|
|
Predominant location of disease
Other
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: First 6 Cycles of treatment (an average of 6 months)Population: All participants except one who was deemed ineligible (treated prior to registration).
Confirmed tumor response was defined to be either a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: * Complete Response (CR): disappearance of all target lesions; * Partial Response (PR) 30% decrease in sum of longest diameter of target lesions;
Outcome measures
| Measure |
Treatment (Carboplatin, Paclitaxel, and Everolimus)
n=45 Participants
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
|
|---|---|
|
Percentage of Participants With Confirmed Tumor Responses
|
36 percentage of participants
Interval 22.0 to 51.0
|
SECONDARY outcome
Timeframe: Time from registration to death or last follow-up (up to 3 years)Population: All participants except one who was deemed ineligible (treated prior to registration).
Overall survival was defined as the time from study enrollment to the time of death from any cause or last follow-up.
Outcome measures
| Measure |
Treatment (Carboplatin, Paclitaxel, and Everolimus)
n=45 Participants
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
|
|---|---|
|
Overall Survival
|
10.1 months
Interval 7.3 to 14.8
|
SECONDARY outcome
Timeframe: Time from registration to the disease progression or death (up to 3 years)Population: All participants except one who was deemed ineligible (treated prior to registration).
The progression-free survival (PFS) was defined as the time from date of registration to the documentation of disease progression or death as a result of any cause, whichever comes first.
Outcome measures
| Measure |
Treatment (Carboplatin, Paclitaxel, and Everolimus)
n=45 Participants
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
|
|---|---|
|
Progression-free Survival
|
4.1 months
Interval 2.8 to 5.7
|
SECONDARY outcome
Timeframe: Up to 3 yearsPopulation: All eligible participants who have achieved an objective response at which the participant's objective status is first noted to be either CR or PR.
Duration of response was defined for all evaluable participants who have achieved an objective response as the date at which the participant's objective status is first noted to be either CR or PR to the date progression is documented.
Outcome measures
| Measure |
Treatment (Carboplatin, Paclitaxel, and Everolimus)
n=16 Participants
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
|
|---|---|
|
Duration of Response
|
5.8 months
Interval 2.5 to 6.8
|
SECONDARY outcome
Timeframe: Up to 3 yearsPopulation: All participant who has been removed from treatment due to progression, adverse events, or refusal.
Time to treatment failure was defined to be the time from the date of registration to the date at which the participant is removed from treatment due to progression, adverse events, or refusal.
Outcome measures
| Measure |
Treatment (Carboplatin, Paclitaxel, and Everolimus)
n=40 Participants
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
|
|---|---|
|
Time to Treatment Failure
|
3.1 months
Interval 1.6 to 4.2
|
Adverse Events
Treatment (Carboplatin, Paclitaxel, and Everolimus)
Serious events: 21 serious events
Other events: 45 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment (Carboplatin, Paclitaxel, and Everolimus)
n=46 participants at risk
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
|
|---|---|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
10.9%
5/46 • Number of events 8 • Up to 3 years
|
|
Cardiac disorders
Cardiac disorder
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Cardiac disorders
Sinus tachycardia
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Gastrointestinal disorders
Abdominal distension
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Gastrointestinal disorders
Abdominal pain
|
4.3%
2/46 • Number of events 2 • Up to 3 years
|
|
Gastrointestinal disorders
Constipation
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
6.5%
3/46 • Number of events 3 • Up to 3 years
|
|
Gastrointestinal disorders
Dysphagia
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Gastrointestinal disorders
Nausea
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Gastrointestinal disorders
Vomiting
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
General disorders
Fatigue
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Infections and infestations
Abdominal infection
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Infections and infestations
Pneumonia
|
2.2%
1/46 • Number of events 2 • Up to 3 years
|
|
Infections and infestations
Sepsis
|
4.3%
2/46 • Number of events 2 • Up to 3 years
|
|
Infections and infestations
Upper respiratory infection
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Investigations
Alkaline phosphatase increased
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Investigations
Leukocyte count decreased
|
10.9%
5/46 • Number of events 5 • Up to 3 years
|
|
Investigations
Neutrophil count decreased
|
32.6%
15/46 • Number of events 18 • Up to 3 years
|
|
Investigations
Platelet count decreased
|
17.4%
8/46 • Number of events 8 • Up to 3 years
|
|
Metabolism and nutrition disorders
Anorexia
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Dehydration
|
4.3%
2/46 • Number of events 2 • Up to 3 years
|
|
Metabolism and nutrition disorders
Serum magnesium decreased
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
4.3%
2/46 • Number of events 2 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Vascular disorders
Thrombosis
|
4.3%
2/46 • Number of events 2 • Up to 3 years
|
Other adverse events
| Measure |
Treatment (Carboplatin, Paclitaxel, and Everolimus)
n=46 participants at risk
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
4.3%
2/46 • Number of events 2 • Up to 3 years
|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
95.7%
44/46 • Number of events 243 • Up to 3 years
|
|
Eye disorders
Extraocular muscle paresis
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Eye disorders
Eye disorder
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Gastrointestinal disorders
Abdominal pain
|
6.5%
3/46 • Number of events 4 • Up to 3 years
|
|
Gastrointestinal disorders
Ascites
|
4.3%
2/46 • Number of events 6 • Up to 3 years
|
|
Gastrointestinal disorders
Constipation
|
4.3%
2/46 • Number of events 2 • Up to 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
45.7%
21/46 • Number of events 48 • Up to 3 years
|
|
Gastrointestinal disorders
Dyspepsia
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
4.3%
2/46 • Number of events 3 • Up to 3 years
|
|
Gastrointestinal disorders
Mucositis oral
|
6.5%
3/46 • Number of events 3 • Up to 3 years
|
|
Gastrointestinal disorders
Nausea
|
69.6%
32/46 • Number of events 93 • Up to 3 years
|
|
Gastrointestinal disorders
Vomiting
|
32.6%
15/46 • Number of events 25 • Up to 3 years
|
|
General disorders
Edema limbs
|
2.2%
1/46 • Number of events 3 • Up to 3 years
|
|
General disorders
Fatigue
|
43.5%
20/46 • Number of events 52 • Up to 3 years
|
|
General disorders
Fever
|
6.5%
3/46 • Number of events 4 • Up to 3 years
|
|
General disorders
Pain
|
4.3%
2/46 • Number of events 8 • Up to 3 years
|
|
Immune system disorders
Cytokine release syndrome
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Immune system disorders
Hypersensitivity
|
26.1%
12/46 • Number of events 15 • Up to 3 years
|
|
Infections and infestations
Bladder infection
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Infections and infestations
Pharyngitis
|
4.3%
2/46 • Number of events 2 • Up to 3 years
|
|
Infections and infestations
Pneumonia
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Infections and infestations
Sinusitis
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Infections and infestations
Skin infection
|
8.7%
4/46 • Number of events 4 • Up to 3 years
|
|
Infections and infestations
Tooth infection
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Infections and infestations
Upper respiratory infection
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Infections and infestations
Urinary tract infection
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Investigations
Activated partial thromboplastin time prolonged
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Investigations
Alanine aminotransferase increased
|
2.2%
1/46 • Number of events 2 • Up to 3 years
|
|
Investigations
Alkaline phosphatase increased
|
8.7%
4/46 • Number of events 10 • Up to 3 years
|
|
Investigations
Aspartate aminotransferase increased
|
6.5%
3/46 • Number of events 4 • Up to 3 years
|
|
Investigations
Forced expiratory volume decreased
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Investigations
Leukocyte count decreased
|
87.0%
40/46 • Number of events 205 • Up to 3 years
|
|
Investigations
Lymphocyte count decreased
|
6.5%
3/46 • Number of events 8 • Up to 3 years
|
|
Investigations
Neutrophil count decreased
|
82.6%
38/46 • Number of events 169 • Up to 3 years
|
|
Investigations
Platelet count decreased
|
67.4%
31/46 • Number of events 174 • Up to 3 years
|
|
Investigations
Serum cholesterol increased
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Investigations
Weight gain
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Investigations
Weight loss
|
4.3%
2/46 • Number of events 4 • Up to 3 years
|
|
Metabolism and nutrition disorders
Anorexia
|
65.2%
30/46 • Number of events 93 • Up to 3 years
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
4.3%
2/46 • Number of events 2 • Up to 3 years
|
|
Metabolism and nutrition disorders
Dehydration
|
10.9%
5/46 • Number of events 9 • Up to 3 years
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
4.3%
2/46 • Number of events 4 • Up to 3 years
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Serum calcium increased
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Serum magnesium decreased
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Serum phosphate decreased
|
2.2%
1/46 • Number of events 3 • Up to 3 years
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Serum potassium increased
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
6.5%
3/46 • Number of events 3 • Up to 3 years
|
|
Metabolism and nutrition disorders
Serum triglycerides increased
|
4.3%
2/46 • Number of events 2 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.5%
3/46 • Number of events 3 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
6.5%
3/46 • Number of events 5 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
10.9%
5/46 • Number of events 10 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
2.2%
1/46 • Number of events 2 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
6.5%
3/46 • Number of events 3 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness upper limb
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.7%
4/46 • Number of events 20 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.3%
2/46 • Number of events 5 • Up to 3 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Nervous system disorders
Dizziness
|
2.2%
1/46 • Number of events 3 • Up to 3 years
|
|
Nervous system disorders
Neuralgia
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Nervous system disorders
Peripheral motor neuropathy
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
34.8%
16/46 • Number of events 46 • Up to 3 years
|
|
Nervous system disorders
Seizure
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Psychiatric disorders
Anxiety
|
4.3%
2/46 • Number of events 3 • Up to 3 years
|
|
Psychiatric disorders
Confusion
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Psychiatric disorders
Insomnia
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Renal and urinary disorders
Glomerular filtration rate decreased
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.3%
2/46 • Number of events 4 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
10.9%
5/46 • Number of events 7 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
10.9%
5/46 • Number of events 7 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
43.5%
20/46 • Number of events 73 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
2.2%
1/46 • Number of events 1 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
4.3%
2/46 • Number of events 2 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
2.2%
1/46 • Number of events 2 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
37.0%
17/46 • Number of events 34 • Up to 3 years
|
|
Vascular disorders
Hypotension
|
2.2%
1/46 • Number of events 4 • Up to 3 years
|
|
Vascular disorders
Thrombosis
|
4.3%
2/46 • Number of events 2 • Up to 3 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60