Docetaxel With or Without Vandetanib in Treating Patients With Metastatic Stomach Cancer or Gastroesophageal Junction Cancer

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00683787
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arms: 3
• Duration (Months): 34
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether docetaxel is more effective when given together with or without vandetanib.

PURPOSE: This randomized phase II trial is studying docetaxel to see how well it works compared with docetaxel given together with vandetanib in treating patients with metastatic stomach cancer or gastroesophageal junction cancer.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer	Drug: docetaxel; Drug: vandetanib	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To test the hypothesis that the addition of a targeted agent, such as vandetanib, to standard chemotherapy with docetaxel will result in incremental responses in patients with metastatic gastric or gastroesophageal junction cancer.

Secondary

• To assess progression-free survival and overall survival of patients treated with this regimen.

• To study the toxicity profile of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical site. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive docetaxel IV once every 3 weeks.

• Arm II: Patients receive docetaxel IV as in arm I and oral vandetanib (100 mg) once daily.

• Arm III: Patients receive docetaxel IV as in arm I and oral vandetanib (300 mg) once daily.

In all arms, courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 2 months for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multicenter Randomized Phase II Trial of Docetaxel With/Without VANDETANIB for Advanced Gastroesophageal Cancer
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I Patients receive docetaxel IV once every 3 weeks.	Drug: docetaxel; Given IV once every 3 weeks
Experimental: Arm II Patients receive docetaxel IV as in arm I and oral vandetanib (100 mg) once daily.	Drug: docetaxel; Given IV once every 3 weeks; Drug: vandetanib; Oral vandetanib once daily
Experimental: Arm III Patients receive docetaxel IV as in arm I and oral vandetanib (300 mg) once daily.	Drug: docetaxel; Given IV once every 3 weeks; Drug: vandetanib; Oral vandetanib once daily

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [1 year]

Secondary Outcome Measures

1. Progression-free Survival [3 years]

2. Overall Survival [3 years]

3. Toxicity [1 year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed gastric adenocarcinoma or gastroesophageal junction cancer

• Metastatic disease

• Measurable disease

• No symptomatic CNS metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

• ECOG performance status 0-1

• Life expectancy ≥ 3 months

• ANC ≥ 1,500/µL

• Platelet count ≥ 100,000/µL

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• Creatinine < 1.5 times ULN OR creatinine clearance ≥ 50 mL/min

• Potassium ≥ 4.0 mEq/L (supplementation allowed) and ≤ the CTCAE grade 1 upper limit

• Magnesium normal (supplementation allowed) and ≤ the CTCAE grade 1 upper limit

• Calcium normal and corrected serum calcium ≤ the CTCAE grade 1 upper limit

• In cases where the serum calcium is below the normal range, calcium (adjusted for albumin) normal OR ionized calcium normal

• ALT and AST ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for up to 12 weeks after completion of study therapy

• Atrial fibrillation allowed if controlled by medication

• LVEF ≥ 45% by MUGA or ECHO

Exclusion criteria:

• Evidence of severe or uncontrolled systemic disease

• Any concurrent condition which makes it undesirable for the patient to participate in the trial or which would jeopardize study compliance, in the Investigator's opinion

• Uncontrolled infection

• Coagulopathy (including warfarin or anti-coagulant related) or bleeding disorder

• Peripheral neuropathy ≥ grade 2

• Clinically significant cardiac event, including myocardial infarction or New York Heart Association class II-IV heart disease within the past 3 months

• Presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia

• History of arrhythmia (i.e., multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) OR asymptomatic sustained ventricular tachycardia

• History of QTc prolongation as a result of other medication that required discontinuation of that medication

• Congenital long QT syndrome or a first degree relative with unexplained sudden death under 40 years of age

• Presence of left bundle branch block

• QTc with Bazett's correction that is unmeasurable or ≥ 480 msec on screening ECG

• If a patient has QTc ≥ 480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart)

• The average OTc from the three screening ECGs must be < 480 msec in order for the patient to be eligible for the study

• Hypertension not controlled by medical therapy (systolic blood pressure [BP] > 160 mm Hg or diastolic BP > 100 mm Hg)

• Currently active diarrhea (≥ grade 2) that may affect the ability of the patient to absorb vandetanib

• Previous or current malignancies of other histologies within the past 5 years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy

• At least 4 weeks since prior chemotherapy or radiotherapy

• No more than one prior chemotherapy regimen for metastatic disease

• Prior adjuvant therapy, including chemoradiotherapy, allowed

• At least 2 weeks since prior palliative radiotherapy

• Up to 3750 cGy palliative radiotherapy to the stomach allowed

• No prior therapy with docetaxel

• More than 30 days since prior investigational agents

• More than 4 weeks since prior and no concurrent or planned participation in another experimental drug study

• More than 4 weeks since prior major surgery and recovered

• More than 2 weeks since prior and no concurrent medication that may cause QTc prolongation or induce Torsades de Pointes

• No concurrent amiodarone

• No concurrent potent inducers of CYP3A4 function (e.g., rifampicin, rifabutin, phenytoin, carbamazepine, barbiturates, or Hypericum perforatum [St. John wort])

• No prior enrollment or randomization to treatment in the present study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001

Sponsors and Collaborators

• Roswell Park Cancer Institute

Investigators

• Principal Investigator: Nikhil Khushalani, MD, Roswell Park Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT00683787
• Other Study ID Numbers: CDR0000596150; RPCI-I-106207
• First Posted: May 23, 2008
• Last Update Posted: Jan 8, 2015
• Last Verified: Dec 1, 2014

• Keywords provided by Roswell Park Cancer Institute: recurrent gastric cancer; stage IV gastric cancer; adenocarcinoma of the stomach
• Additional relevant MeSH terms: Stomach Neoplasms; Docetaxel

Study Results

Participant Flow

Arm/Group Title	Arm A: Docetaxel	Arm B: Docetaxel+VANDETANIB (100 mg)	Arm C: Docetaxel+VANDETANIB (300 mg)
Arm/Group Description	Patients receive docetaxel IV once every 3 weeks. docetaxel: Given IV once every 3 weeks	Patients receive docetaxel IV as in arm I and oral vandetanib (100 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily	Patients receive docetaxel IV as in arm I and oral vandetanib (300 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily
Period Title: Overall Study
STARTED	3	3	2
COMPLETED	0	0	0
NOT COMPLETED	3	3	2

Baseline Characteristics

Arm/Group Title	Arm A: Docetaxel	Arm B: Docetaxel+VANDETANIB (100 mg)	Arm C: Docetaxel+VANDETANIB (300 mg)	Total
Arm/Group Description	Patients receive docetaxel IV once every 3 weeks. docetaxel: Given IV once every 3 weeks	Patients receive docetaxel IV as in arm I and oral vandetanib (100 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily	Patients receive docetaxel IV as in arm I and oral vandetanib (300 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily	Total of all reporting groups
Overall Participants	3	3	2	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.67 (7.64)	67 (3.61)	60 (8.49)	61.38 (7.37)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	0 0%	0 0%	1 12.5%
Male	2 66.7%	3 100%	2 100%	7 87.5%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and inadequate number of patients no statistical inference of the primary and secondary aims were carried forth.

Arm/Group Title	Arm A: Docetaxel	Arm B: Docetaxel+VANDETANIB (100 mg)	Arm C: Docetaxel+VANDETANIB (300 mg)
Arm/Group Description	Patients receive docetaxel IV once every 3 weeks. docetaxel: Given IV once every 3 weeks	Patients receive docetaxel IV as in arm I and oral vandetanib (100 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily	Patients receive docetaxel IV as in arm I and oral vandetanib (300 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily
Measure Participants	0	0	0

2. Secondary Outcome

Title	Progression-free Survival
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and inadequate number of patients no statistical inference of the primary and secondary aims were carried forth.

Arm/Group Title	Arm A: Docetaxel	Arm B: Docetaxel+VANDETANIB (100 mg)	Arm C: Docetaxel+VANDETANIB (300 mg)
Arm/Group Description	Patients receive docetaxel IV once every 3 weeks. docetaxel: Given IV once every 3 weeks	Patients receive docetaxel IV as in arm I and oral vandetanib (100 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily	Patients receive docetaxel IV as in arm I and oral vandetanib (300 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily
Measure Participants	0	0	0

3. Secondary Outcome

Title	Overall Survival
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and inadequate number of patients no statistical inference of the primary and secondary aims were carried forth.

Arm/Group Title	Arm A: Docetaxel	Arm B: Docetaxel+VANDETANIB (100 mg)	Arm C: Docetaxel+VANDETANIB (300 mg)
Arm/Group Description	Patients receive docetaxel IV once every 3 weeks. docetaxel: Given IV once every 3 weeks	Patients receive docetaxel IV as in arm I and oral vandetanib (100 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily	Patients receive docetaxel IV as in arm I and oral vandetanib (300 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily
Measure Participants	0	0	0

4. Secondary Outcome

Title	Toxicity
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and inadequate number of patients no statistical inference of the primary and secondary aims were carried forth.

Arm/Group Title	Arm A: Docetaxel	Arm B: Docetaxel+VANDETANIB (100 mg)	Arm C: Docetaxel+VANDETANIB (300 mg)
Arm/Group Description	Patients receive docetaxel IV once every 3 weeks. docetaxel: Given IV once every 3 weeks	Patients receive docetaxel IV as in arm I and oral vandetanib (100 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily	Patients receive docetaxel IV as in arm I and oral vandetanib (300 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily
Measure Participants	0	0	0

Adverse Events

Arm/Group Title	Arm A: Docetaxel		Arm B: Docetaxel+VANDETANIB (100 mg)		Arm C: Docetaxel+VANDETANIB (300 mg)
Arm/Group Description	Patients receive docetaxel IV once every 3 weeks. docetaxel: Given IV once every 3 weeks		Patients receive docetaxel IV as in arm I and oral vandetanib (100 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily		Patients receive docetaxel IV as in arm I and oral vandetanib (300 mg) once daily. docetaxel: Given IV once every 3 weeks vandetanib: Oral vandetanib once daily
All Cause Mortality
	Arm A: Docetaxel		Arm B: Docetaxel+VANDETANIB (100 mg)		Arm C: Docetaxel+VANDETANIB (300 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A: Docetaxel		Arm B: Docetaxel+VANDETANIB (100 mg)		Arm C: Docetaxel+VANDETANIB (300 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		2/3 (66.7%)		0/2 (0%)
Blood and lymphatic system disorders
Febrile neutropenia	1/3 (33.3%)	1	1/3 (33.3%)	1	0/2 (0%)	0
Infections and infestations
Pneumonia	0/3 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A: Docetaxel		Arm B: Docetaxel+VANDETANIB (100 mg)		Arm C: Docetaxel+VANDETANIB (300 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		2/2 (100%)
Blood and lymphatic system disorders
Anaemia	0/3 (0%)	0	0/3 (0%)	0	1/2 (50%)	1
Leukopenia	1/3 (33.3%)	2	2/3 (66.7%)	3	1/2 (50%)	1
Lymphopenia	2/3 (66.7%)	3	2/3 (66.7%)	7	1/2 (50%)	1
Neutropenia	1/3 (33.3%)	1	2/3 (66.7%)	3	1/2 (50%)	1
Cardiac disorders
Palpitations	0/3 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
Eye disorders
Dry eye	1/3 (33.3%)	1	0/3 (0%)	0	0/2 (0%)	0
Gastrointestinal disorders
Abdominal pain	2/3 (66.7%)	3	1/3 (33.3%)	1	0/2 (0%)	0
Constipation	2/3 (66.7%)	2	1/3 (33.3%)	1	0/2 (0%)	0
Diarrhoea	1/3 (33.3%)	4	0/3 (0%)	0	2/2 (100%)	7
Dysphagia	1/3 (33.3%)	1	2/3 (66.7%)	2	1/2 (50%)	1
Nausea	3/3 (100%)	7	1/3 (33.3%)	1	1/2 (50%)	1
Retching	0/3 (0%)	0	0/3 (0%)	0	1/2 (50%)	1
Stomatitis	1/3 (33.3%)	1	1/3 (33.3%)	1	1/2 (50%)	1
Vomiting	2/3 (66.7%)	7	2/3 (66.7%)	2	1/2 (50%)	1
General disorders
Chest pain	1/3 (33.3%)	1	0/3 (0%)	0	0/2 (0%)	0
Chills	2/3 (66.7%)	2	0/3 (0%)	0	1/2 (50%)	1
Fatigue	3/3 (100%)	7	2/3 (66.7%)	3	2/2 (100%)	5
Mucosal inflammation	2/3 (66.7%)	3	2/3 (66.7%)	3	0/2 (0%)	0
Oedema peripheral	1/3 (33.3%)	2	0/3 (0%)	0	0/2 (0%)	0
Pain	1/3 (33.3%)	1	0/3 (0%)	0	2/2 (100%)	3
Pyrexia	1/3 (33.3%)	1	1/3 (33.3%)	1	0/2 (0%)	0
Infections and infestations
Infection	1/3 (33.3%)	1	1/3 (33.3%)	1	0/2 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	0/3 (0%)	0	1/3 (33.3%)	3	0/2 (0%)	0
Alanine aminotransferase increased	0/3 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
Aspartate aminotransferase	0/3 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
Aspartate aminotransferase increased	1/3 (33.3%)	1	1/3 (33.3%)	2	0/2 (0%)	0
Blood alkaline phosphatase	1/3 (33.3%)	1	2/3 (66.7%)	3	2/2 (100%)	2
Blood creatine increased	1/3 (33.3%)	1	0/3 (0%)	0	0/2 (0%)	0
Blood creatinine	0/3 (0%)	0	1/3 (33.3%)	3	0/2 (0%)	0
Electrocardiogram QT corrected interval	0/3 (0%)	0	1/3 (33.3%)	1	1/2 (50%)	3
Electrocardiogram QT corrected interval prolonged	0/3 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
Electrocardiogram QT prolonged	0/3 (0%)	0	1/3 (33.3%)	1	1/2 (50%)	2
Haemoglobin	1/3 (33.3%)	1	1/3 (33.3%)	2	0/2 (0%)	0
International normalised ratio	0/3 (0%)	0	1/3 (33.3%)	2	0/2 (0%)	0
Neutrophil count	0/3 (0%)	0	0/3 (0%)	0	1/2 (50%)	1
Neutrophil count decreased	2/3 (66.7%)	2	1/3 (33.3%)	1	0/2 (0%)	0
Platelet count decreased	1/3 (33.3%)	1	0/3 (0%)	0	0/2 (0%)	0
White blood cell count decreased	0/3 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
Metabolism and nutrition disorders
Anorexia	1/3 (33.3%)	1	1/3 (33.3%)	1	1/2 (50%)	1
Decreased appetite	1/3 (33.3%)	1	0/3 (0%)	0	0/2 (0%)	0
Dehydration	2/3 (66.7%)	2	1/3 (33.3%)	2	1/2 (50%)	1
Gout	1/3 (33.3%)	2	0/3 (0%)	0	0/2 (0%)	0
Hyperglycaemia	2/3 (66.7%)	3	2/3 (66.7%)	3	1/2 (50%)	3
Hyperkalaemia	1/3 (33.3%)	1	1/3 (33.3%)	2	0/2 (0%)	0
Hypernatraemia	0/3 (0%)	0	0/3 (0%)	0	1/2 (50%)	1
Hypoalbuminaemia	1/3 (33.3%)	1	1/3 (33.3%)	3	0/2 (0%)	0
Hypocalcaemia	0/3 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
Hypoglycaemia	1/3 (33.3%)	1	1/3 (33.3%)	1	1/2 (50%)	1
Hypokalaemia	0/3 (0%)	0	1/3 (33.3%)	1	1/2 (50%)	2
Hypomagnesaemia	0/3 (0%)	0	0/3 (0%)	0	1/2 (50%)	2
Hyponatraemia	3/3 (100%)	4	1/3 (33.3%)	1	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/3 (33.3%)	1	0/3 (0%)	0	1/2 (50%)	1
Back pain	0/3 (0%)	0	1/3 (33.3%)	2	1/2 (50%)	1
Bone pain	1/3 (33.3%)	1	0/3 (0%)	0	0/2 (0%)	0
Myalgia	3/3 (100%)	3	0/3 (0%)	0	0/2 (0%)	0
Nervous system disorders
Dizziness	1/3 (33.3%)	2	1/3 (33.3%)	1	1/2 (50%)	2
Dysgeusia	1/3 (33.3%)	1	1/3 (33.3%)	1	0/2 (0%)	0
Headache	0/3 (0%)	0	0/3 (0%)	0	1/2 (50%)	1
Neuropathy	1/3 (33.3%)	2	0/3 (0%)	0	1/2 (50%)	1
Peripheral sensory neuropathy	0/3 (0%)	0	1/3 (33.3%)	7	1/2 (50%)	1
Psychiatric disorders
Confusional state	0/3 (0%)	0	0/3 (0%)	0	1/2 (50%)	1
Insomnia	1/3 (33.3%)	1	2/3 (66.7%)	2	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/3 (33.3%)	2	1/3 (33.3%)	1	0/2 (0%)	0
Dyspnoea	2/3 (66.7%)	2	1/3 (33.3%)	1	1/2 (50%)	2
Skin and subcutaneous tissue disorders
Alopecia	2/3 (66.7%)	3	1/3 (33.3%)	1	0/2 (0%)	0
Dermatitis acneiform	2/3 (66.7%)	6	0/3 (0%)	0	0/2 (0%)	0
Hyperhidrosis	1/3 (33.3%)	1	1/3 (33.3%)	1	0/2 (0%)	0
Nail disorder	0/3 (0%)	0	1/3 (33.3%)	2	0/2 (0%)	0
Palmar-plantar erythrodysaesthesia syndrome	2/3 (66.7%)	2	0/3 (0%)	0	1/2 (50%)	1
Photosensitivity reaction	0/3 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
Rash	1/3 (33.3%)	2	0/3 (0%)	0	1/2 (50%)	1

Limitations/Caveats

Due to the study's early termination and inadequate number of patients no statistical inference of the primary and secondary aims were carried forth.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.