Trial Outcomes & Findings for Phase I Trial of Oral Metronomic Topotecan and Oral Pazopanib to Treat Recurrent/Persistent Gynecologic Tumors (NCT NCT00800345)
NCT ID: NCT00800345
Last Updated: 2017-03-28
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
33 participants
Primary outcome timeframe
Cycle 1 (28 days)
Results posted on
2017-03-28
Participant Flow
Participant milestones
| Measure |
Experimental
Metronomic oral topotecan and oral pazopanib will be administered by mouth beginning on Cycle 1 Day 1. Patients will be enrolled and observed for dose limiting toxicity (DLT) for 1 cycle of treatment. Dose modification of the combination will depend on the number of patients experiencing DLT(s) at each dose level.
Oral Topotecan: Starting on Cycle 1 Day 1, each subject will receive the assigned dose of topotecan administered by mouth.
Pazopanib: Starting on Cycle 1 Day 1, each subject will receive the assigned dose of pazopanib administered by mouth.
|
|---|---|
|
Overall Study
STARTED
|
33
|
|
Overall Study
COMPLETED
|
33
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase I Trial of Oral Metronomic Topotecan and Oral Pazopanib to Treat Recurrent/Persistent Gynecologic Tumors
Baseline characteristics by cohort
| Measure |
Experimental
n=33 Participants
Metronomic oral topotecan and oral pazopanib will be administered by mouth beginning on Cycle 1 Day 1. Patients will be enrolled and observed for dose limiting toxicity (DLT) for 1 cycle of treatment. Dose modification of the combination will depend on the number of patients experiencing DLT(s) at each dose level.
Oral Topotecan: Starting on Cycle 1 Day 1, each subject will receive the assigned dose of topotecan administered by mouth.
Pazopanib: Starting on Cycle 1 Day 1, each subject will receive the assigned dose of pazopanib administered by mouth.
|
|---|---|
|
Age, Continuous
|
61.88 years
STANDARD_DEVIATION 12.81 • n=5 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
33 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (28 days)Outcome measures
| Measure |
Experimental
n=33 Participants
Metronomic oral topotecan and oral pazopanib will be administered by mouth beginning on Cycle 1 Day 1. Patients will be enrolled and observed for dose limiting toxicity (DLT) for 1 cycle of treatment. Dose modification of the combination will depend on the number of patients experiencing DLT(s) at each dose level.
Oral Topotecan: Starting on Cycle 1 Day 1, each subject will receive the assigned dose of topotecan administered by mouth.
Pazopanib: Starting on Cycle 1 Day 1, each subject will receive the assigned dose of pazopanib administered by mouth.
|
|---|---|
|
Dose Limiting Toxicity (DLT)
Experienced a DLT
|
8 participants
|
|
Dose Limiting Toxicity (DLT)
Did not experience a DLT
|
23 participants
|
|
Dose Limiting Toxicity (DLT)
Unevaluable
|
2 participants
|
SECONDARY outcome
Timeframe: After every 2 cycles of treatment beginning on Cycle 1 Day 1, up to 38 monthsTreatment response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is \>=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of \>=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions.
Outcome measures
| Measure |
Experimental
n=33 Participants
Metronomic oral topotecan and oral pazopanib will be administered by mouth beginning on Cycle 1 Day 1. Patients will be enrolled and observed for dose limiting toxicity (DLT) for 1 cycle of treatment. Dose modification of the combination will depend on the number of patients experiencing DLT(s) at each dose level.
Oral Topotecan: Starting on Cycle 1 Day 1, each subject will receive the assigned dose of topotecan administered by mouth.
Pazopanib: Starting on Cycle 1 Day 1, each subject will receive the assigned dose of pazopanib administered by mouth.
|
|---|---|
|
Treatment Response
Complete Response
|
4 participants
|
|
Treatment Response
Partial Response
|
5 participants
|
|
Treatment Response
Stable Disease
|
13 participants
|
|
Treatment Response
Progressive Disease
|
10 participants
|
|
Treatment Response
Not Evaluable
|
1 participants
|
Adverse Events
Experimental
Serious events: 11 serious events
Other events: 33 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Experimental
n=33 participants at risk
Metronomic oral topotecan and oral pazopanib will be administered by mouth beginning on Cycle 1 Day 1. Patients will be enrolled and observed for dose limiting toxicity (DLT) for 1 cycle of treatment. Dose modification of the combination will depend on the number of patients experiencing DLT(s) at each dose level.
Oral Topotecan: Starting on Cycle 1 Day 1, each subject will receive the assigned dose of topotecan administered by mouth.
Pazopanib: Starting on Cycle 1 Day 1, each subject will receive the assigned dose of pazopanib administered by mouth.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
3.0%
1/33
|
|
Cardiac disorders
Cardiac failure congestive
|
3.0%
1/33
|
|
Cardiac disorders
Myocardial ischaemia
|
3.0%
1/33
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
3.0%
1/33
|
|
Hepatobiliary disorders
Cholecystitis
|
3.0%
1/33
|
|
Infections and infestations
Bacteraemia
|
3.0%
1/33
|
|
Infections and infestations
Bronchitis
|
3.0%
1/33
|
|
Infections and infestations
Cellulitis
|
3.0%
1/33
|
|
Injury, poisoning and procedural complications
Overdose
|
3.0%
1/33
|
|
Investigations
Alanine aminotransferase increased
|
3.0%
1/33
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.0%
1/33
|
|
Metabolism and nutrition disorders
Dehydration
|
3.0%
1/33
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
3.0%
1/33
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
3.0%
1/33
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
3.0%
1/33
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
3.0%
1/33
|
|
Vascular disorders
Hypotension
|
3.0%
1/33
|
|
Vascular disorders
Jugular vein thrombosis
|
3.0%
1/33
|
|
Vascular disorders
Orthostatic hypotension
|
3.0%
1/33
|
Other adverse events
| Measure |
Experimental
n=33 participants at risk
Metronomic oral topotecan and oral pazopanib will be administered by mouth beginning on Cycle 1 Day 1. Patients will be enrolled and observed for dose limiting toxicity (DLT) for 1 cycle of treatment. Dose modification of the combination will depend on the number of patients experiencing DLT(s) at each dose level.
Oral Topotecan: Starting on Cycle 1 Day 1, each subject will receive the assigned dose of topotecan administered by mouth.
Pazopanib: Starting on Cycle 1 Day 1, each subject will receive the assigned dose of pazopanib administered by mouth.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
27.3%
9/33
|
|
Blood and lymphatic system disorders
Neutropenia
|
33.3%
11/33
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
24.2%
8/33
|
|
Cardiac disorders
Palpitations
|
3.0%
1/33
|
|
Cardiac disorders
Sinus tachycardia
|
3.0%
1/33
|
|
Cardiac disorders
Tachycardia
|
3.0%
1/33
|
|
Ear and labyrinth disorders
Cerumen impaction
|
6.1%
2/33
|
|
Ear and labyrinth disorders
Hypoacusis
|
3.0%
1/33
|
|
Endocrine disorders
Hypothyroidism
|
12.1%
4/33
|
|
Eye disorders
Ocular hyperaemia
|
3.0%
1/33
|
|
Gastrointestinal disorders
Abdominal distension
|
3.0%
1/33
|
|
Gastrointestinal disorders
Abdominal pain
|
18.2%
6/33
|
|
Gastrointestinal disorders
Abdominal pain lower
|
3.0%
1/33
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.1%
2/33
|
|
Gastrointestinal disorders
Constipation
|
9.1%
3/33
|
|
Gastrointestinal disorders
Diarrhoea
|
60.6%
20/33
|
|
Gastrointestinal disorders
Dyspepsia
|
9.1%
3/33
|
|
Gastrointestinal disorders
Flatulence
|
15.2%
5/33
|
|
Gastrointestinal disorders
Gastrointestinal fistula
|
3.0%
1/33
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
3.0%
1/33
|
|
Gastrointestinal disorders
Haemorrhoids
|
3.0%
1/33
|
|
Gastrointestinal disorders
Nausea
|
69.7%
23/33
|
|
Gastrointestinal disorders
Oral disorder
|
3.0%
1/33
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
3.0%
1/33
|
|
Gastrointestinal disorders
Stomatitis
|
24.2%
8/33
|
|
Gastrointestinal disorders
Toothache
|
3.0%
1/33
|
|
Gastrointestinal disorders
Vomiting
|
54.5%
18/33
|
|
General disorders
Catheter site pain
|
3.0%
1/33
|
|
Hepatobiliary disorders
Chest discomfort
|
3.0%
1/33
|
|
General disorders
Chills
|
3.0%
1/33
|
|
General disorders
Fatigue
|
60.6%
20/33
|
|
General disorders
Influenza like illness
|
3.0%
1/33
|
|
General disorders
Mucosal inflammation
|
6.1%
2/33
|
|
General disorders
Oedema peripheral
|
15.2%
5/33
|
|
General disorders
Pyrexia
|
9.1%
3/33
|
|
General disorders
Tenderness
|
3.0%
1/33
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
3.0%
1/33
|
|
Immune system disorders
Allergy to arthropod sting
|
3.0%
1/33
|
|
Immune system disorders
Drug hypersensitivity
|
6.1%
2/33
|
|
Infections and infestations
Bacteraemia
|
3.0%
1/33
|
|
Infections and infestations
Bronchitis
|
3.0%
1/33
|
|
Infections and infestations
Cellulitis
|
3.0%
1/33
|
|
Infections and infestations
Device related infection
|
3.0%
1/33
|
|
Infections and infestations
Fungal infection
|
3.0%
1/33
|
|
Infections and infestations
Herpes zoster
|
3.0%
1/33
|
|
Infections and infestations
Infection
|
3.0%
1/33
|
|
Infections and infestations
Oral candidiasis
|
3.0%
1/33
|
|
Infections and infestations
Oral herpes
|
3.0%
1/33
|
|
Infections and infestations
Sinusitis
|
15.2%
5/33
|
|
Infections and infestations
Upper respiratory tract infection
|
18.2%
6/33
|
|
Infections and infestations
Urinary tract infection
|
36.4%
12/33
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
3.0%
1/33
|
|
Injury, poisoning and procedural complications
Administration related reaction
|
3.0%
1/33
|
|
Injury, poisoning and procedural complications
Contusion
|
3.0%
1/33
|
|
Investigations
Alanine aminotransferase increased
|
21.2%
7/33
|
|
Investigations
Aspartate aminotransferase increased
|
18.2%
6/33
|
|
Investigations
Blood alkaline phosphatase increased
|
6.1%
2/33
|
|
Investigations
Blood creatinine increased
|
3.0%
1/33
|
|
Investigations
Lipase increased
|
3.0%
1/33
|
|
Investigations
Neutrophil count decreased
|
6.1%
2/33
|
|
Investigations
Platelet count decreased
|
3.0%
1/33
|
|
Investigations
Weight decreased
|
30.3%
10/33
|
|
Investigations
White blood cell count decreased
|
3.0%
1/33
|
|
Metabolism and nutrition disorders
Decreased appetite
|
21.2%
7/33
|
|
Metabolism and nutrition disorders
Dehydration
|
6.1%
2/33
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
9.1%
3/33
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
3.0%
1/33
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
15.2%
5/33
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
30.3%
10/33
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
3.0%
1/33
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
3.0%
1/33
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.0%
1/33
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
18.2%
6/33
|
|
Musculoskeletal and connective tissue disorders
Medial tibial stress syndrome
|
3.0%
1/33
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
18.2%
6/33
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.1%
2/33
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.1%
3/33
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
3.0%
1/33
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.1%
4/33
|
|
Musculoskeletal and connective tissue disorders
Plantar fasciitis
|
3.0%
1/33
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
3.0%
1/33
|
|
Nervous system disorders
Anosmia
|
3.0%
1/33
|
|
Nervous system disorders
Dizziness
|
6.1%
2/33
|
|
Nervous system disorders
Dysgeusia
|
54.5%
18/33
|
|
Nervous system disorders
Headache
|
24.2%
8/33
|
|
Nervous system disorders
Hypoaesthesia
|
3.0%
1/33
|
|
Nervous system disorders
Neuropathy peripheral
|
3.0%
1/33
|
|
Nervous system disorders
Transient ischaemic attack
|
3.0%
1/33
|
|
Nervous system disorders
Tremor
|
6.1%
2/33
|
|
Psychiatric disorders
Anxiety
|
12.1%
4/33
|
|
Psychiatric disorders
Depression
|
6.1%
2/33
|
|
Psychiatric disorders
Insomnia
|
6.1%
2/33
|
|
Psychiatric disorders
Restlessness
|
3.0%
1/33
|
|
Renal and urinary disorders
Dysuria
|
3.0%
1/33
|
|
Renal and urinary disorders
Haematuria
|
3.0%
1/33
|
|
Renal and urinary disorders
Hydronephrosis
|
6.1%
2/33
|
|
Renal and urinary disorders
Pollakiuria
|
3.0%
1/33
|
|
Renal and urinary disorders
Proteinuria
|
30.3%
10/33
|
|
Renal and urinary disorders
Urinary tract disorder
|
6.1%
2/33
|
|
Reproductive system and breast disorders
Female genital tract fistula
|
3.0%
1/33
|
|
Reproductive system and breast disorders
Hydrometra
|
3.0%
1/33
|
|
Reproductive system and breast disorders
Pelvic pain
|
3.0%
1/33
|
|
Reproductive system and breast disorders
Vaginal fistula
|
3.0%
1/33
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
3.0%
1/33
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.1%
4/33
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
3.0%
1/33
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
15.2%
5/33
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
6.1%
2/33
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
3.0%
1/33
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.1%
2/33
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus discomfort
|
6.1%
2/33
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
3.0%
1/33
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
6.1%
2/33
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
3.0%
1/33
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
3.0%
1/33
|
|
Skin and subcutaneous tissue disorders
Erythemas
|
3.0%
1/33
|
|
Skin and subcutaneous tissue disorders
Hair colour changes
|
27.3%
9/33
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
3.0%
1/33
|
|
Skin and subcutaneous tissue disorders
Increased tendency to bruise
|
3.0%
1/33
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
6.1%
2/33
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
3.0%
1/33
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
3.0%
1/33
|
|
Skin and subcutaneous tissue disorders
Pigmentation disorder
|
3.0%
1/33
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
3.0%
1/33
|
|
Skin and subcutaneous tissue disorders
Rash
|
15.2%
5/33
|
|
Skin and subcutaneous tissue disorders
Skin hypopigmentation
|
6.1%
2/33
|
|
Skin and subcutaneous tissue disorders
Skin mass
|
3.0%
1/33
|
|
Surgical and medical procedures
Sinus operation
|
3.0%
1/33
|
|
Vascular disorders
Deep vein thrombosis
|
3.0%
1/33
|
|
Vascular disorders
Flushing
|
3.0%
1/33
|
|
Vascular disorders
Haematoma
|
3.0%
1/33
|
|
Vascular disorders
Haemorrhage
|
3.0%
1/33
|
|
Vascular disorders
Hypertension
|
15.2%
5/33
|
|
Vascular disorders
Lymphoedema
|
3.0%
1/33
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60