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Recurrent Skin CancerPhase 1/2NCT01465815

Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)

A Phase 1/2 study testing erlotinib hydrochloride, linsitinib and radiation therapy in people with Recurrent Skin Cancer and Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, run by OHSU Knight Cancer Institute at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I/II trial studies the side effects and best dose of linsitinib when given together with erlotinib hydrochloride and radiation therapy after surgery in treating patients with advanced or recurrent head and neck cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
erlotinib hydrochloride, linsitinib and radiation therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteUnited States
Study dates
Dec 2011to Sep 2013
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

  • Patients must have primary or recurrent advanced-stage (III/IV) squamous cell carcinoma of the skin of the face, ear, scalp or neck or of the lip
  • A biopsy or preserved representative tumor block is required to confirm the diagnosis
  • Patients must be surgical candidates with resectable disease; macroscopic complete resection of all tumor must be planned with curative intent
  • Patients must be willing to receive postoperative radiation therapy and treatment with study drugs
  • Both men and women and members of all races and ethnic groups will be included
  • Life expectancy of greater than 12 months
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  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count >= 1,500/microliter(uL)
  • Hemoglobin >= 9 g/dL
  • Platelets >= 100,000/uL
  • International normalized ratio (INR) < institutional upper limit of normal (ULN)
  • Total bilirubin =< 1.5 x institutional ULN
  • Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) =< 2.5 X institutional ULN
  • Creatinine =< 1.5 X institutional ULN
  • Fasting blood glucose < 125 mg/dL at baseline
  • Patients-both males and females-with reproductive potential (i.e., menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study; women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients with known distant metastasis
  • Patients who have had prior radiation treatment of the index cancer or area of disease
  • Patients who have received any other investigational medication within 6 weeks of enrollment, or who are scheduled to receive an investigational drug during the course of the study
  • Prior treatment with EGFR inhibitor for index cancer
  • Prior treatment with an IGF-1R antagonist (small molecule inhibitor or antibody)
  • Breast-feeding, pregnancy or of childbearing potential (including less than two years postmenopausal) and unable to confirm adequate contraception due to possible risk to fetus or infant
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  • Insulin-dependent and non-insulin dependent diabetes mellitus including any metformin or insulin use on an ongoing basis prior to enrollment
  • Known severe hypersensitivity to erlotinib, other small molecule inhibitors of EGFR, or its excipients
  • Hepatitis B or C infection (acute or chronic), known human immunodeficiency virus (HIV), or active uncontrolled infection, because of possible risk of lethal infection when treated with marrow suppressive therapy
  • History of uncontrolled cardiac disease such as unstable angina pectoris, myocardial infarction within prior 6 months, untreated coronary artery disease, uncontrolled congestive heart failure, or cardiomyopathy with decreased ejection fraction
  • Uncontrolled peptic or gastric ulcer disease or gastrointestinal bleeding within prior 6 months
  • Corrected QT interval (QTc) > 450 msec; congenital long QT syndrome or previous history of QTc prolongation as a result from other medication
  • Presence of left bundle branch block (LBBB); QTc with Bazett's correction that is unmeasurable, or >= 450 msec on screening electrocardiogram (EKG)
  • Any concomitant medication that may cause QTc prolongation or concomitant medication that is associated with Torsades de Pointes
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Active smokers unwilling to quit smoking during treatment
  • Use of the potent cytochrome P450 3A4 (CYP3A4) and cytochrome P450 1A2 (CYP1A2) inhibitors is not allowed; other less potent CYP3A4 and CYP1A2 inhibitors/inducers are not excluded
  • Participation in another investigational trial while on this study is not allowed
  • History of poorly controlled gastrointestinal disorders including acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, Crohn's disease, ulcerative colitis or other diseases which have the potential for bowel perforation
  • Other malignancies except for resected cervical cancer in situ

Trial locations and contacts

1 site in 1 country.

United States1 site

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: Phase I/II Study of Postoperative Adjuvant Chemoradiation for cSCCHN

This phase I/II trial studies the side effects and best dose of linsitinib when given together with erlotinib hydrochloride and radiation therapy after surgery in treating patients with advanced or recurrent head and neck cancer. Erlotinib hydrochloride and linsitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy together with erlotinib hydrochloride and linsitinib may kill more tumor cells. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the MTD (maximally tolerated dose) of OSI-906 (linsitinib) when used in combination with erlotinib (erlotinib hydrochloride) and radiation therapy after surgery for advanced-stage cutaneous squamous cell carcinoma of the head and neck (cSCCHN). (Phase I) II. To estimate the 2-year overall survival (OS) compared to historical controls. (Phase II)

SECONDARY OBJECTIVES:

  1. To determine the safety and tolerability of OSI-906 in combination with erlotinib and radiation therapy after surgery for advanced-stage cSCCHN.

II. To estimate the 2-year disease specific and disease free survival. III. To determine the time to recurrence and patterns of failure. IV. To evaluate the effects of short-term preoperative treatment with erlotinib and OSI-906 on the expression epidermal growth factor receptor (EGFR), insulin-like growth factor 1 receptor (IGF-1R) and parallel or downstream molecular targets in cSCCHN in one third of the patients.

OUTLINE:

Optional non-therapeutic (biomarker) portion: Patients are randomized to 1 of 3 treatment arms.

Arm A: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) and linsitinib PO twice daily (BID) on days 1-7 or 1-14.

Arm B: Patients receive erlotinib hydrochloride PO QD and placebo PO QD or BID on days 1-7 or 1-14.

Arm C: Patients receive linsitinib PO BID and placebo PO QD or BID on days 1-7 or 1-14.

Treatment continues until 1 day before planned surgical resection (for up to 28 days if surgery is delayed).

Therapeutic portion: This is a phase I dose-escalation study of linsitinib followed by a phase II study.

Patients undergo standard QD conventional radiotherapy at the discretion of the treating physician. Patients receive concurrent linsitinib PO BID and erlotinib hydrochloride PO QD during the entire course of radiation in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 6 and 12 weeks, every 12-16 weeks for 2 years, every 6 months for 3 years, and then annually thereafter.

Being tested
erlotinib hydrochloride, linsitinib, placebo, radiation therapy, therapeutic conventional surgery
Medical subject headings
Skin Neoplasms

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 PO

  • linsitinibDrug

    Also called OSI-906

    Given PO

  • placeboDrug

    Also called PLCB

    Given PO

  • radiation therapyRadiation

    Also called irradiation, radiotherapy, therapy, radiation

    Undergo radiation therapy

  • therapeutic conventional surgeryProcedure or surgery

    Undergo planned surgery

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01465815
Study groupRoleWhat they receive
Treatment (adjuvant enzyme inhibitor and radiation therapy)ExperimentalOptional non-therapeutic (biomarker) portion: Patients are randomized to 1 of 3 treatment arms. Arm A: Patients receive erlotinib hydrochloride PO QD and linsitinib PO BID on days 1-7 or 1-14. Treatment continues until 1 day before planned surgical resection (for up to 28 days if surgery is delayed). Therapeutic portion: This is a phase I dose-escalation study of linsitinib followed by a phase II study. Patients undergo standard QD conventional radiotherapy at the discretion of the treating physician. Patients receive concurrent linsitinib PO BID and erlotinib hydrochloride PO QD during the entire course of radiation in the absence of disease progression or unacceptable toxicity.
Receives: Drug: erlotinib hydrochloride; Drug: linsitinib; Radiation: radiation therapy; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis
Erlotinib and Placebo (Sugar Pill)ExperimentalArm B: Patients receive erlotinib hydrochloride PO QD and placebo PO QD or BID on days 1-7 or 1-14. Treatment continues until 1 day before planned surgical resection (for up to 28 days if surgery is delayed). Therapeutic portion: This is a phase I dose-escalation study of linsitinib followed by a phase II study. Patients undergo standard QD conventional radiotherapy at the discretion of the treating physician. Patients receive concurrent linsitinib PO BID and erlotinib hydrochloride PO QD during the entire course of radiation in the absence of disease progression or unacceptable toxicity.
Receives: Drug: erlotinib hydrochloride; Drug: placebo
OSI-906 and Placebo (Sugar Pill)ExperimentalArm C: Patients receive linsitinib PO BID and placebo PO QD or BID on days 1-7 or 1-14. Treatment continues until 1 day before planned surgical resection (for up to 28 days if surgery is delayed). Therapeutic portion: This is a phase I dose-escalation study of linsitinib followed by a phase II study. Patients undergo standard QD conventional radiotherapy at the discretion of the treating physician. Patients receive concurrent linsitinib PO BID and erlotinib hydrochloride PO QD during the entire course of radiation in the absence of disease progression or unacceptable toxicity.
Receives: Drug: linsitinib; Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with overall survival(OS) after two years of treatment (Phase II)

    The 2-year OS and 95% confidence interval will be determined using Kaplan-Meier method.

    Measured: Up to 2 years

  2. The maximum tolerated dose (MTD) of linsitinib when used in combination with erlotinib hydrochloride and radiation therapy (phase 1)

    The MTD of linsitinib when used in combination with erlotinib hydrochloride and radiation therapy will be determined using a standard 3x3 dose-escalation scheme. The dose limiting toxicity (DLT) will be defined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.02). DLT is defined as any grade 3 non-hematologic toxicity attributed to treatment or grade 4 hematologic toxicity, neutropenic fever requiring hospitalization, or treatment delay due to hematologic toxicity.

    Measured: up to 24 months

  3. The maximum tolerated dose (MTD) of linsitinib when used in combination with erlotinib hydrochloride and radiation therapy (phase 1)

    The MTD of linsitinib when used in combination with erlotinib hydrochloride and radiation therapy will be determined using a standard 3x3 dose-escalation scheme. The dose limiting toxicity (DLT) will be defined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events CTCAE (v4.02). DLT is defined as any grade 3 non-hematologic toxicity attributed to treatment or grade 4 hematologic toxicity, neutropenic fever requiring hospitalization, or treatment delay due to hematologic toxicity.

    Measured: Up to 5 years

Secondary outcomes (6)

  1. Number of participants with disease free survival

    Measured: At 2 years

  2. Time to recurrence and patterns of failure

    Measured: Up to 2 years

  3. Effects of short-term preoperative treatment with erlotinib hydrochloride and linsitinib on the expression EGFR, IGF-1R and parallel or downstream molecular targets in cSCCHN in one third of the patients

    Measured: From baseline to time of surgery (after 7-14 days of study drug administration)

  4. Number of adverse events observed from linsitinib in combination with erlotinib hydrochloride and radiation therapy.

    Measured: After completion of study therapy at 6 and 12 weeks

  5. Number of adverse events observed from linsitinib in combination with erlotinib hydrochloride and radiation therapy

    Measured: Every 12-16 weeks for 2 years

  6. Number of adverse events observed from linsitinib in combination with erlotinib hydrochloride and radiation therapy

    Measured: Every 6 months for 3 years and then annually thereafter

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2011 (estimated)
  2. Study startDec 2011
  3. Primary completionSep 2013
  4. Study completionSep 2013

Why it stopped: Drug manufacturer, Astellas Pharma, informed us that safety and efficacy of Erlotinib and OSI-906 in other oncology studies was determined to be unfavorable.

Resources

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01465815
Sponsor's protocol ID
6901 (5466)
Other IDs
NCI-2011-01225
Status last verified
Nov 2014
First submitted
26 Oct 2011
Last updated
19 Nov 2014
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing erlotinib hydrochloride, linsitinib and radiation therapy in people with Recurrent Skin Cancer and Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, run by OHSU Knight Cancer Institute 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 17 inclusion and 20 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: withdrawn, as of the sponsor's last update on 19 Nov 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 was withdrawn before enrolling participants, so there are no results.

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?

Number of participants with overall survival(OS) after two years of treatment (Phase II) (time frame: Up to 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01465815.

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 19 Nov 2014.

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