Trial Outcomes & Findings for Treatment Based on Molecular Profiling Diagnosis Carcinoma of Unknown Primary Site (NCT NCT00737243)
NCT ID: NCT00737243
Last Updated: 2016-08-17
Results Overview
Defined as the elapsed time from the start of treatment to the date of death from any cause or lost to follow-up. Participants lost to follow up were censored as of the last date known to be alive.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
289 participants
Primary outcome timeframe
every 6-8 weeks (2 cycles) until death from any cause or lost to follow up, projected 18 months
Results posted on
2016-08-17
Participant Flow
Between October 2008 and December 2011, 289 subjects in the United States with CUP were enrolled and had a molecular assay of biopsy tissue. 252 (87%) subjects had a successful assay performed; 223 subjects were treated and 29 were withdrawn (16 no longer met eligibility criteria and 13 were removed because of patient decision).
252 subjects had successful assays. 223 subjects were treated and 29 were withdrawn prior to treatment. 194 received assay-directed therapy; 29 received empiric CUP therapy. Patients receiving assay-directed therapy were divided into 2 groups: 1) more responsive tumour type; and 2) less responsive tumour type.
Participant milestones
| Measure |
All Patients With a Successful Tumor Assays Performed
Subjects in this group had a successful molecular assay of biopsy tissue
|
|---|---|
|
Overall Study
STARTED
|
289
|
|
Overall Study
Successful Assay Performed
|
252
|
|
Overall Study
Insufficient Tissue for Assay, Withdrawn
|
37
|
|
Overall Study
Treated
|
223
|
|
Overall Study
Not Treated
|
29
|
|
Overall Study
Site Specific Therapy More Responsive
|
115
|
|
Overall Study
Site Specific Therapy Less Responsive
|
79
|
|
Overall Study
Empiric CUP Therapy
|
29
|
|
Overall Study
COMPLETED
|
194
|
|
Overall Study
NOT COMPLETED
|
95
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Treatment Based on Molecular Profiling Diagnosis Carcinoma of Unknown Primary Site
Baseline characteristics by cohort
| Measure |
Patients With Tumor Assays Performed
n=252 Participants
Of 289 patients initially enrolled, 252 had successful assays performed. 37 patients had insufficient tissue for assay and came off study.
|
|---|---|
|
Age, Continuous
|
64 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
136 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
116 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
252 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: every 6-8 weeks (2 cycles) until death from any cause or lost to follow up, projected 18 monthsPopulation: Of 223 treated patients: 194 received assay-directed therapy; 29 received empiric CUP therapy. The 194 patients who received assay-directed therapy were separated into groups based on predicted responsiveness of the tumor type for further analysis.
Defined as the elapsed time from the start of treatment to the date of death from any cause or lost to follow-up. Participants lost to follow up were censored as of the last date known to be alive.
Outcome measures
| Measure |
More Treatment Responsive
n=115 Participants
Patients who received assay-directed therapy for tumor types with a predicted median survival ≥ 12 months.
|
Less Treatment Responsive
n=79 Participants
Patients who received assay-directed therapy for tumors with a predicted median survival ≤ 12 months
|
|---|---|---|
|
Overall Survival
|
13.43 months
Interval 10.57 to 16.03
|
7.62 months
Interval 6.04 to 15.11
|
SECONDARY outcome
Timeframe: at baselinePopulation: Of 252 participants analyzed, the assay correctly predicted the tissue of origin in 247 patients (98%). The predicted tissue of origin could not be determined in 5 participants (2%).
To evaluate the utility of the assay in identifying the tissue of origin in patients with carcinoma of unknown primary site (CUP), an archived tumor specimen was assayed upon study entry. If a tissue of origin was predicted by the assay, participants received standard site-specific therapy for that tumor type. When tissue of origin was not predicted by the assay, patients received standard empiric chemotherapy for CUP and were not followed further. If the assay was not completed due to inadequate amount of tumor in the biopsy specimen, patients were not treated on the study.
Outcome measures
| Measure |
More Treatment Responsive
n=252 Participants
Patients who received assay-directed therapy for tumor types with a predicted median survival ≥ 12 months.
|
Less Treatment Responsive
Patients who received assay-directed therapy for tumors with a predicted median survival ≤ 12 months
|
|---|---|---|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Biliary tract (gallbladder, bile duct)
|
52 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Urothelium
|
31 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Colorectum
|
28 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Non-small cell lung
|
27 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Pancreas
|
12 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Breast
|
12 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Ovary
|
11 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Gastroesophageal
|
10 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Kidney
|
9 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Liver
|
8 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Sarcoma
|
6 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Cervix
|
6 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Neuroendocrine
|
5 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Prostate
|
4 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Germ cell
|
4 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Skin, squamous
|
4 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Carcinoid, intestine
|
3 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Mesothelioma
|
3 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Thyroid
|
2 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Endometrium
|
2 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Melanoma
|
2 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Skin, basal-cell
|
2 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Lung, small-cell
|
1 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Lymphoma
|
1 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Head and Neck
|
1 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
Adrenal
|
1 participants
|
—
|
|
Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
unclassifiable
|
5 participants
|
—
|
Adverse Events
All Treated Patients
Serious events: 30 serious events
Other events: 74 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Treated Patients
n=223 participants at risk
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
1.8%
4/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Cardiac disorders
Atrial Fibrillation
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Cardiac disorders
Cardiac disorders - Other, left ventricular diastolic dysfunction
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Psychiatric disorders
Confusion
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Gastrointestinal disorders
Constipation
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
General disorders
Death NOS
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.90%
2/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Gastrointestinal disorders
Diarrhea
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.90%
2/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Esophageal ulcer
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
General disorders
Fatigue
|
0.90%
2/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.90%
2/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
General disorders
Fever
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, small bowel obstruction
|
0.90%
2/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other, hepatic dysfunction
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Infections and infestations
Infections and infestations - Other, infection at port site
|
0.90%
2/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Infections and infestations
Infections and infestations - Other, pneumonia
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Infections and infestations
Infections and infestations - Other, unspecified
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Investigations
INR increased
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Nervous system disorders
Ischemia cerebrovascular
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
1.3%
3/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Investigations
Neutrophil count decreased
|
0.90%
2/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
General disorders
Non-cardiac chest pain
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Investigations
Platelet count decreased
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.90%
2/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Infections and infestations
sepsis
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Infections and infestations
Skin infection
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Vascular disorders
Thromboembolic event
|
0.90%
2/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Infections and infestations
Urinary tract infection
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.45%
1/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
1.8%
4/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
Other adverse events
| Measure |
All Treated Patients
n=223 participants at risk
|
|---|---|
|
Investigations
Platelet count decreased
|
9.9%
22/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
General disorders
Fatigue
|
9.4%
21/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Investigations
Neutrophil count decreased
|
8.1%
18/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Blood and lymphatic system disorders
Anemia
|
6.7%
15/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
|
Investigations
White blood cell decreased
|
6.3%
14/223 • every 6-8 weeks (2 cycles) up to 48 weeks
Adverse event data were collected for 223 participants treated with at least one dose of study drug.
|
Additional Information
John D. Hainsworth, MD
Sarah Cannon Research Institute
Phone: 1-877-691-7274
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 but =180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites
- Publication restrictions are in place
Restriction type: OTHER