A Study of Vismodegib (GDC-0449) in Patients Treated With Vismodegib in a Previous Genentech-sponsored Phase I or II Cancer Study

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00959647
• Collaborator: (none)
• Enrollment: 19
• Locations: 10
• Arm: 1
• Duration (Months): 52
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This was a multicenter, open-label extension study. Patients who received vismodegib (GDC-0449) in a Genentech-sponsored study and who had completed the parent study or who continued to receive vismodegib at the time the parent study closed were eligible for continued treatment in this protocol.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer; Basal Cell Carcinoma; Metastatic Colorectal Cancer	Drug: Vismodegib; Drug: FOLFOX; Drug: FOLFIRI; Drug: Bevacizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multicenter Extension Study of GDC-0449 (Hedgehog Pathway Inhibitor) in Patients Treated With GDC-0449 in a Previous Genentech-sponsored Phase I or Phase II Cancer Study
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Vismodegib 150 mg Participants received 150 mg vismodegib orally once a day until disease progression, intolerable toxicity, or withdrawal from the study. If a participant had been receiving combination chemotherapy and/or biotherapy (FOLFOX, FOLFIRI, bevacizumab) in a parent study, the same combination chemotherapy and/or biotherapy as specified in the parent study could be continued in this study at the discretion of the investigator.

Drug: Vismodegib; Vismodegib was supplied in capsules.; Other Names: Erivedge GDC-0449 RO5450815 ; Drug: FOLFOX; FOLFOX (folinic acid [FOL, leucovorin], fluorouracil [F, 5-FU], and oxaliplatin [OX]) was supplied as solutions for intravenous administration.; Drug: FOLFIRI; FOLFIRI (folinic acid [FOL, leucovorin], fluorouracil [F, 5-FU], and irinotecan [IRI]) was supplied as solutions for intravenous administration.; Drug: Bevacizumab; Bevacizumab was supplied as a solution for intravenous administration.; Other Names: Avastin

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Experienced at Least 1 Adverse Event [Baseline until 30 days following the last administration of study treatment]

2. Percentage of Participants Who Discontinued Treatment Due to an Adverse Event [Baseline until 30 days following the last administration of study treatment]

Secondary Outcome Measures

1. Incidence and Severity of All Adverse Events and Serious Adverse Events [30 days following the last administration of study treatment]

2. Incidence of Adverse Events Leading to GDC-0449 Discontinuation [30 days following the last administration of study treatment]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

This study only enrolled participants who took part in previous studies of vismodegib conducted by Genentech.

Inclusion Criteria:

• Completed vismodegib treatment within 2-4 weeks in a Genentech-sponsored parent study or continued to receive vismodegib at the time the Genentech-sponsored parent study closed.

• Expectation by the investigator that the participant may continue to benefit from additional vismodegib treatment.

Exclusion Criteria:

• Intervening anti-tumor therapy not specified in the parent study (ie, non-protocol-specified chemotherapy, other targeted therapy, radiation therapy, or photodynamic therapy).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Scottsdale	Arizona	United States	85258
2		Oakland	California	United States	94609
3		Palm Springs	California	United States	92262
4		Stanford	California	United States	94305
5		Baltimore	Maryland	United States	21231
6		Ann Arbor	Michigan	United States	48109-0934
7		Detroit	Michigan	United States	48201
8		Las Vegas	Nevada	United States	89106
9		Cincinnati	Ohio	United States	45242
10		Houston	Texas	United States	77030

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Josina Reddy, MD, PhD, Genentech, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT00959647
• Other Study ID Numbers: SHH4437g; GO01352
• First Posted: Aug 14, 2009
• Last Update Posted: Jan 7, 2015
• Last Verified: Dec 1, 2014

• Keywords provided by Genentech, Inc.: Hedgehog pathway inhibitor
• Additional relevant MeSH terms: Carcinoma, Basal Cell; Bevacizumab

Study Results

Participant Flow

Arm/Group Title	Vismodegib 150 mg
Arm/Group Description	Participants received 150 mg vismodegib orally once a day until disease progression, intolerable toxicity, or withdrawal from the study. If a participant had been receiving combination chemotherapy and/or biotherapy (FOLFOX, FOLFIRI, bevacizumab) in a parent study, the same combination chemotherapy and/or biotherapy as specified in the parent study could be continued in this study at the discretion of the investigator.
Period Title: Overall Study
STARTED	19
COMPLETED	0
NOT COMPLETED	19

Baseline Characteristics

Arm/Group Title	Vismodegib 150 mg
Arm/Group Description	Participants received 150 mg vismodegib orally once a day until disease progression, intolerable toxicity, or withdrawal from the study. If a participant had been receiving combination chemotherapy and/or biotherapy (FOLFOX, FOLFIRI, bevacizumab) in a parent study, the same combination chemotherapy and/or biotherapy as specified in the parent study could be continued in this study at the discretion of the investigator.
Overall Participants	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.4 (15.4)
Sex: Female, Male (Count of Participants)
Female	4 21.1%
Male	15 78.9%

Outcome Measures

1. Secondary Outcome

Title	Incidence and Severity of All Adverse Events and Serious Adverse Events
Time Frame	30 days following the last administration of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

2. Secondary Outcome

Title	Incidence of Adverse Events Leading to GDC-0449 Discontinuation
Time Frame	30 days following the last administration of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Primary Outcome

Title	Percentage of Participants Who Experienced at Least 1 Adverse Event
Time Frame	Baseline until 30 days following the last administration of study treatment

Outcome Measure Data

Analysis Population Description

Safety population: All participants who had received at least 1 dose of study medication.

Arm/Group Title	Vismodegib 150 mg
Arm/Group Description	Participants received 150 mg vismodegib orally once a day until disease progression, intolerable toxicity, or withdrawal from the study. If a participant had been receiving combination chemotherapy and/or biotherapy (FOLFOX, FOLFIRI, bevacizumab) in a parent study, the same combination chemotherapy and/or biotherapy as specified in the parent study could be continued in this study at the discretion of the investigator.
Measure Participants	19
Number [Percentage of participants]	89.5 471.1%

4. Primary Outcome

Title	Percentage of Participants Who Discontinued Treatment Due to an Adverse Event
Time Frame	Baseline until 30 days following the last administration of study treatment

Outcome Measure Data

Analysis Population Description

Safety population: All participants who had received at least 1 dose of study medication.

Arm/Group Title	Vismodegib 150 mg
Arm/Group Description	Participants received 150 mg vismodegib orally once a day until disease progression, intolerable toxicity, or withdrawal from the study. If a participant had been receiving combination chemotherapy and/or biotherapy (FOLFOX, FOLFIRI, bevacizumab) in a parent study, the same combination chemotherapy and/or biotherapy as specified in the parent study could be continued in this study at the discretion of the investigator.
Measure Participants	19
Number [Percentage of participants]	10.5 55.3%

Adverse Events

Time Frame	From Baseline until 30 days following the last administration of study treatment.
Adverse Event Reporting Description	Safety population: All participants who had received at least 1 dose of study medication.
Arm/Group Title	Vismodegib 150 mg
Arm/Group Description	Participants received 150 mg vismodegib orally once a day until disease progression, intolerable toxicity, or withdrawal from the study. If a participant had been receiving combination chemotherapy and/or biotherapy (FOLFOX, FOLFIRI, bevacizumab) in a parent study, the same combination chemotherapy and/or biotherapy as specified in the parent study could be continued in this study at the discretion of the investigator.
All Cause Mortality
	Vismodegib 150 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vismodegib 150 mg
	Affected / at Risk (%)	# Events
Total	3/19 (15.8%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/19 (5.3%)
Hepatobiliary disorders
Bile duct obstruction	1/19 (5.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	1/19 (5.3%)
Reproductive system and breast disorders
Tubo-ovarian abscess	1/19 (5.3%)
Other (Not Including Serious) Adverse Events
	Vismodegib 150 mg
	Affected / at Risk (%)	# Events
Total	17/19 (89.5%)
Blood and lymphatic system disorders
Anaemia	3/19 (15.8%)
Anaemia macrocytic	1/19 (5.3%)
Iron deficiency anaemia	1/19 (5.3%)
Eye disorders
Dry eye	1/19 (5.3%)
Eyelid cyst	1/19 (5.3%)
Vision blurred	1/19 (5.3%)
Gastrointestinal disorders
Diarrhoea	10/19 (52.6%)
Nausea	6/19 (31.6%)
Constipation	5/19 (26.3%)
Flatulence	3/19 (15.8%)
Vomiting	3/19 (15.8%)
Gastritis	2/19 (10.5%)
Abdominal discomfort	1/19 (5.3%)
Abdominal pain upper	1/19 (5.3%)
Dental caries	1/19 (5.3%)
Dyspepsia	1/19 (5.3%)
Gastrointestinal haemorrhage	1/19 (5.3%)
Inguinal hernia	1/19 (5.3%)
General disorders
Fatigue	8/19 (42.1%)
Pyrexia	2/19 (10.5%)
Asthenia	1/19 (5.3%)
Chest pain	1/19 (5.3%)
Hernia	1/19 (5.3%)
Influenza like illness	1/19 (5.3%)
Local swelling	1/19 (5.3%)
Oedema peripheral	1/19 (5.3%)
Pain	1/19 (5.3%)
Polyp	1/19 (5.3%)
Swelling	1/19 (5.3%)
Immune system disorders
Seasonal allergy	1/19 (5.3%)
Infections and infestations
Upper respiratory tract infection	2/19 (10.5%)
Cellulitis	1/19 (5.3%)
Herpes zoster	1/19 (5.3%)
Purulent discharge	1/19 (5.3%)
Rash pustular	1/19 (5.3%)
Respiratory tract infection	1/19 (5.3%)
Sinusitis	1/19 (5.3%)
Urinary tract infection	1/19 (5.3%)
Injury, poisoning and procedural complications
Contusion	1/19 (5.3%)
Excoriation	1/19 (5.3%)
Incision site pain	1/19 (5.3%)
Laceration	1/19 (5.3%)
Muscle strain	1/19 (5.3%)
Post procedural discharge	1/19 (5.3%)
Procedural pain	1/19 (5.3%)
Rib fracture	1/19 (5.3%)
Investigations
Weight decreased	6/19 (31.6%)
Hepatic enzyme increased	2/19 (10.5%)
Aspartate aminotransferase increased	1/19 (5.3%)
Blood bilirubin increased	1/19 (5.3%)
Blood pressure increased	1/19 (5.3%)
Prostatic specific antigen increased	1/19 (5.3%)
Metabolism and nutrition disorders
Decreased appetite	3/19 (15.8%)
Hypokalaemia	3/19 (15.8%)
Dehydration	2/19 (10.5%)
Hyperglycaemia	1/19 (5.3%)
Hyperlipidaemia	1/19 (5.3%)
Hypomagnesaemia	1/19 (5.3%)
Lactose intolerance	1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Muscle spasms	9/19 (47.4%)
Arthralgia	2/19 (10.5%)
Arthritis	1/19 (5.3%)
Back pain	1/19 (5.3%)
Muscular weakness	1/19 (5.3%)
Musculoskeletal chest pain	1/19 (5.3%)
Myalgia	1/19 (5.3%)
Spinal osteoarthritis	1/19 (5.3%)
Trismus	1/19 (5.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	1/19 (5.3%)
Metastases to bone	1/19 (5.3%)
Tumour pain	1/19 (5.3%)
Nervous system disorders
Dysgeusia	6/19 (31.6%)
Dizziness	3/19 (15.8%)
Headache	1/19 (5.3%)
Parkinson's disease	1/19 (5.3%)
Parosmia	1/19 (5.3%)
Psychiatric disorders
Insomnia	4/19 (21.1%)
Anxiety	2/19 (10.5%)
Renal and urinary disorders
Haematuria	1/19 (5.3%)
Nocturia	1/19 (5.3%)
Urinary straining	1/19 (5.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/19 (10.5%)
Epistaxis	1/19 (5.3%)
Lung disorder	1/19 (5.3%)
Nasal congestion	1/19 (5.3%)
Rhinorrhoea	1/19 (5.3%)
Skin and subcutaneous tissue disorders
Alopecia	6/19 (31.6%)
Ecchymosis	2/19 (10.5%)
Rash	2/19 (10.5%)
Rash pruritic	2/19 (10.5%)
Actinic keratosis	1/19 (5.3%)
Eczema	1/19 (5.3%)
Erythema	1/19 (5.3%)
Hyperhidrosis	1/19 (5.3%)
Hyperkeratosis	1/19 (5.3%)
Rash follicular	1/19 (5.3%)
Vascular disorders
Hot flush	1/19 (5.3%)
Hypertension	1/19 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.