Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell CarcinomaPhase 1/2NCT00101348
Erlotinib and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Kidney, Colorectal, Head and Neck, Pancreatic, or Non-Small Cell Lung Cancer
A Phase 1/2 study testing erlotinib hydrochloride, cetuximab and bevacizumab in people with Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma and Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This randomized phase I/II trial studies the side effects, best way to give, and best dose of erlotinib and bevacizumab when given with cetuximab and how well giving erlotinib and cetuximab together with or without bevacizumab works in treating patients with metastatic or unresectable kidney, colorectal, head and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Basal Cell Carcinoma of the Lip
- What is being tested?
- erlotinib hydrochloride, cetuximab and bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to May 2008
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- One of the following histologically confirmed diagnoses:
- Renal cell cancer
- Clear cell histology
- Metastatic or unresectable disease AND meets 1 of the following criteria:
- Recurrent disease
- Refractory to interleukin-2 (IL-2)- or interferon-based therapy
Show all 76Show fewer
- Previously untreated AND not a candidate for IL-2-based therapy
- Colorectal, head and neck, pancreatic, or non-small cell lung cancer
- Metastatic or unresectable disease
- Progression after prior standard treatment
- No evidence of CNS disease, including the following (part 2 only):
- Primary brain tumor
- Brain metastases
- Paraffin embedded tumor blocks available
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100%
- More than 12 weeks
- Absolute neutrophil count ≥ 1,500 mm^3
- Platelet count ≥ 100,000 mm^3
- Bilirubin ≤ 1.5 mg/dL
- AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastasis is present)
- PTT and INR ≤ 1.5, unless receiving full-dose warfarin (part 2 only)
- Creatinine ≤ 1.5 times ULN
- Creatinine clearance ≥ 60 mL/min
- Calcium < 10 mg/dL (hypocalcemic agents allowed)
- No proteinuria*
- Protein < 1 g on 24-hour urine collection*
- No unstable angina pectoris
- No cardiac arrhythmia
- No symptomatic congestive heart failure
- None of the following are allowed for part 2:
- Myocardial infarction within the past 6 months
- New York Heart Association class II-IV heart disease
- Serious cardiac arrhythmia requiring medication
- Peripheral vascular disease ≥ grade II
- Recent history of cerebrovascular accident
- Uncontrolled hypertension (blood pressure ≥ 150/85 mm Hg despite medication)
- Other clinically significant cardiovascular disease
- No gastrointestinal (GI) tract disease resulting in an inability to take oral medication
- No GI tract disease resulting in a requirement for IV alimentation
- No active peptic ulcer disease
- No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drugs
- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (part 2 only)
- No ongoing or active infection
- No active infection requiring parenteral antibiotics (part 2 only)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 2 months after study treatment
- No significant traumatic injury within the past 28 days (part 2 only)
- No history of abnormalities of the cornea (e.g., dry eye syndrome, Sjögren's syndrome, or congenital abnormality [e.g., Fuch's dystrophy])
- No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the breast or cervix
- No psychiatric illness or social situation that would preclude study compliance
- No serious or non-healing wound ulcer or bone fracture (part 2 only)
- No other uncontrolled illness
- See Disease Characteristics
- More than 4 weeks since prior immunotherapy
- No prior cetuximab
- No prior bevacizumab
- Concurrent epoetin alfa or darbepoetin alfa allowed
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- More than 4 weeks since prior radiotherapy
- No prior surgical procedures affecting absorption
- Prior nephrectomy or resection of metastatic lesions allowed provided patient has fully recovered
- More than 7 days since prior core biopsy*
- More than 28 days since prior major surgery or open biopsy*
- No concurrent major surgery*
- Recovered from all prior therapy
- No prior erlotinib
- Concurrent bisphosphonates allowed
- Concurrent full-dose anticoagulants allowed provided the following criteria are met (part 2 only):
- In-range INR (usually between 2 and 3) AND on a stable dose of warfarin or low molecular weight heparin
- No active bleeding
- No pathological conditions that carry a high risk of bleeding (e.g., tumor involving major vessels or varices)
- No other concurrent investigational agents
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer therapy
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
Official title: A Phase I, and Biologic Correlative Study of Erlotinib, in Combination With Cetuximab and Bevacizumab in Patients With Metastatic Renal Cell Carcinoma
This randomized phase I/II trial studies the side effects, best way to give, and best dose of erlotinib and bevacizumab when given with cetuximab and how well giving erlotinib and cetuximab together with or without bevacizumab works in treating patients with metastatic or unresectable kidney, colorectal, head and neck, pancreatic, or non-small cell lung cancer. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab and bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving erlotinib together with cetuximab and/or bevacizumab may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose (MTD) of erlotinib when combined with cetuximab in patients with metastatic or unresectable renal cell, colorectal, head and neck, pancreatic, or non-small cell lung cancer (part 1).
II. Determine the MTD of bevacizumab when combined with cetuximab and erlotinib in these patients (part 2).
III. Determine the toxic effects, both quantitatively and qualitatively, of these regimens in these patients.
IV. Determine the antitumor activity of these regimens, in terms of tumor response, short-term survival, and progression-free survival, in these patients.
SECONDARY OBJECTIVES:
- Compare, preliminarily, the toxicity and antitumor activity profiles of these regimens in these patients.
OUTLINE: This is an open-label, multicenter, dose-escalation study of erlotinib and bevacizumab.
Part 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22.
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Part 2: Patients receive erlotinib as in part 1 at the MTD and cetuximab as in part 1. Patients also receive bevacizumab IV over 1½ hours on day 1 and over 1 hour on day 15.
Cohorts of 3-6 patients receive escalating doses of bevacizumab until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
In both groups, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
After completion of study treatment, patients are followed at 1 month.
- Conditions
- Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Basal Cell Carcinoma of the Lip, Recurrent Colon Cancer, Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
- Being tested
- erlotinib hydrochloride, cetuximab, bevacizumab, laboratory biomarker analysis
- Medical subject headings
- Colonic Neoplasms, Esthesioneuroblastoma, Olfactory, Carcinoma, Non-Small-Cell Lung, Pancreatic Neoplasms, Rectal Neoplasms, Salivary Gland Neoplasms, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
erlotinib hydrochlorideDrug
Also called CP-358,774, erlotinib, OSI-774
Given orally
cetuximabBiological
Also called C225, C225 monoclonal antibody, IMC-C225, MOAB C225
Given IV
bevacizumabBiological
Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (erlotinib hydrochloride, cetuximab, bevacizumab) | Experimental | Part 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22.
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Part 2: Patients receive erlotinib as in part 1 at the MTD and cetuximab as in part 1. Patients also receive bevacizumab IV over 1½ hours on day 1 and over 1 hour on day 15.
Cohorts of 3-6 patients receive escalating doses of bevacizumab until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
In both groups, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Receives: Drug: erlotinib hydrochloride; Biological: cetuximab; Biological: bevacizumab; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of erlotinib hydrochloride combined with cetuximab determined by dose-limiting toxicities (DLT) graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3 (Part I)
The occurrence and maximal grade of toxicity for the whole duration of treatment will be listed and tabulated by type.
Measured: 28 days
MTD of bevacizumab combined with cetuximab and erlotinib hydrochloride determined by DLT graded according to the CTCAE version 3 (Part II)
The occurrence and maximal grade of toxicity for the whole duration of treatment will be listed and tabulated by type.
Measured: 28 days
Secondary outcomes (3)
Antitumor activity defined as the number and extent (complete or partial) objective responses as well as objective stable disease as measured by RECIST criteria
The estimated rate and their 95% confidence interval, will be reported.
Measured: 6 months
Median time to progression
Measured: Up to 1 month
Progression-free survival
Measured: From the start of the treatment until the date the criteria for progression are met or the date the patient is taken off study for any reason, assessed up to 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2005 (estimated)
- Study startJan 2005
- Primary completionOct 2007
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Alain Mita, Principal investigator, Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00101348
- Sponsor's protocol ID
- NCI-2012-02639
- Other IDs
- NCI-2012-02639, CDR0000401514, NCI-6588, CTRC-IDD-0332, 6588, U01CA069853, P30CA054174
- Status last verified
- Dec 2012
- First submitted
- 7 Jan 2005
- Last updated
- 11 Jun 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, and Biologic Correlative Study of Erlotinib, in Combination With Cetuximab and Bevacizumab in Patients With Metastatic Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT00101348
- Acronym / sponsor ID
- NCI-2012-02639
- Conditions
- Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Basal Cell Carcinoma of the Lip, Recurrent Colon Cancer, Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 2005
- Primary completion
- Oct 2007 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 10 Jan 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase I/II trial studies the side effects, best way to give, and best dose of erlotinib and bevacizumab when given with cetuximab and how well giving erlotinib and cetuximab together with or without bevacizumab works in treating patients with metastatic or unresectable kidney, colorectal, head and neck, pancreatic, or non-small cell lung cancer. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab and bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving erlotinib together with cetuximab and/or bevacizumab may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose (MTD) of erlotinib when combined with cetuximab in patients with metastatic or unresectable renal cell, colorectal, head and neck, pancreatic, or non-small cell lung cancer (part 1).
II. Determine the MTD of bevacizumab when combined with cetuximab and erlotinib in these patients (part 2).
III. Determine the toxic effects, both quantitatively and qualitatively, of these regimens in these patients.
IV. Determine the antitumor activity of these regimens, in terms of tumor response, short-term survival, and progression-free survival, in these patients.
SECONDARY OBJECTIVES:
- Compare, preliminarily, the toxicity and antitumor activity profiles of these regimens in these patients.
OUTLINE: This is an open-label, multicenter, dose-escalation study of erlotinib and bevacizumab.
Part 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22.
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Part 2: Patients receive erlotinib as in part 1 at the MTD and cetuximab as in part 1. Patients also receive bevacizumab IV over 1½ hours on day 1 and over 1 hour on day 15.
Cohorts of 3-6 patients receive escalating doses of bevacizumab until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
In both groups, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
After completion of study treatment, patients are followed at 1 month.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (erlotinib hydrochloride, cetuximab, bevacizumab) | Experimental | Drug: erlotinib hydrochloride, Biological: cetuximab, Biological: bevacizumab, Other: laboratory biomarker analysisPart 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Part 2: Patients receive erlotinib as in part 1 at the MTD and cetuximab as in part 1. Patients also receive bevacizumab IV over 1½ hours on day 1 and over 1 hour on day 15. Cohorts of 3-6 patients receive escalating doses of bevacizumab until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. In both groups, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (76 listed)
- One of the following histologically confirmed diagnoses:
- No evidence of CNS disease, including the following (part 2 only):
- Paraffin embedded tumor blocks available
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100%
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| erlotinib hydrochlorideAlso: CP-358,774, erlotinib, OSI-774Given orally | Drug | Treatment (erlotinib hydrochloride, cetuximab, bevacizumab) |
| cetuximabAlso: C225, C225 monoclonal antibody, IMC-C225, MOAB C225Given IV | Biological | Treatment (erlotinib hydrochloride, cetuximab, bevacizumab) |
| bevacizumabAlso: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGFGiven IV | Biological | Treatment (erlotinib hydrochloride, cetuximab, bevacizumab) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (erlotinib hydrochloride, cetuximab, bevacizumab) |
Primary outcome
Maximum tolerated dose (MTD) of erlotinib hydrochloride combined with cetuximab determined by dose-limiting toxicities (DLT) graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3 (Part I)
Time frame: 28 days
The occurrence and maximal grade of toxicity for the whole duration of treatment will be listed and tabulated by type.
MTD of bevacizumab combined with cetuximab and erlotinib hydrochloride determined by DLT graded according to the CTCAE version 3 (Part II)
Time frame: 28 days
The occurrence and maximal grade of toxicity for the whole duration of treatment will be listed and tabulated by type.
3 secondary outcomes
Antitumor activity defined as the number and extent (complete or partial) objective responses as well as objective stable disease as measured by RECIST criteria
Time frame: 6 months
Median time to progression
Time frame: Up to 1 month
Progression-free survival
Time frame: From the start of the treatment until the date the criteria for progression are met or the date the patient is taken off study for any reason, assessed up to 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alain Mita principal investigator
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing erlotinib hydrochloride, cetuximab and bevacizumab in people with Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma and Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 76 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) of erlotinib hydrochloride combined with cetuximab determined by dose-limiting toxicities (DLT) graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3 (Part I) (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2014.