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Squamous Cell CarcinomaPhase 1NCT00966472

Phase I Study of a Statin + Erlotinib for Advanced Solid Malignancies With Focus on Squamous Cell Carcinomas and NSCLC

A Phase 1 study testing Erlotinib + Rosuvastatin in people with Squamous Cell Carcinoma and Non-Small Cell Lung Cancer, run by Ottawa Hospital Research Institute at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine the recommended phase II dose (RP2D) of rosuvastatin that can be given in combination with standard erlotinib treatment in patients with advanced incurable squamous cell cancer and NSCLC. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Erlotinib + Rosuvastatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteCanada
Study dates
Mar 2009to Sep 2014
Phase
Phase 1
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically documented advanced and/or metastatic incurable tumor (especially squamous cell carcinoma or NSCLC).
  • Clinically or radiologically documented (measurable or evaluable)disease.
  • 18 years or older and less than 70 years of age.
  • ECOG performance status: 0, 1 or 2
  • No previous therapy with EGFR inhibitor (monoclonal antibody or TKI).
  • Must have recovered from any treatment related toxicities prior to registration.
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  • Curative radiotherapy must be completed at least 3 months prior to registration
  • Palliative radiotherapy is permitted providing a minimum of 14 days have elapsed between the end of radiotherapy and registration onto the study and patients have recovered from any acute toxic effects from radiation prior to registration.
  • Previous surgery is permitted provided wound healing has occurred and at least 14 days have elapsed prior to registration if surgery was major.
  • Adequate hematopoietic, hepatic and renal function defined as follows: hemoglobin >= 90g/L, platelets > 100 x 10^9/L, bilirubin <1.5 x ULN, ALT or AST <1.5 x ULN, proteinuria < grade 1, normal thyroid function (normal TSH or free T4 level after correction), serum creatinine institution normal limits or calculated creatinine clearance > 60 mls/min (except for patients with cervical cancer who require a creatinine clearance of 72 mls/min.)
  • Women must be post menopausal, surgically sterile or use two reliable forms of contraception. Women of childbearing potential must have a serum or urine pregnancy test taken and proven negative within 7 days prior to registration. Men must be surgically sterile or use a barrier method of contraception
  • Accessible for repeat dosing and follow-up

Who cannot join

  • Asian ethnicity (Filipino, Chinese, Japanese, Korean, Vietnamese, or South Asian origin)
  • History of other malignancies, except adequately treated non-melanoma skin cancer or other solid tumors curatively treated with no evidence of disease for > 5 years.
  • Untreated brain or meningeal metastases. Patients with treated and radiologic or clinical evidence of stable brain metastases are eligible providing that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 4 weeks prior to registration).
  • Untreated and/or uncontrolled cardiovascular conditions and/or symptomatic cardiac dysfunction.
  • Active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol.
  • Concurrent treatment with other experimental drugs or anti-cancer therapy.
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  • Patients who require oral anticoagulants (coumadin, warfarin) are eligible provided there is strict vigilance with respect to monitoring INR. The investigator should consider switching these patients to LMW heparin or an oral anti-platelet agent such as aspirin
  • Patients who are taking concomitant medications, which are highly protein bound, nephrotoxic, or which are known strong inhibitors or inducers of the hepatic p450 (especially CYP3A4) system, which have not been discontinued prior to study registration. Caution should be exercised, and patients monitored closely, for patients taking concomitant drugs with the potential to inhibit or induce the hepatic p450 (especially CYP3A4) system.
  • Any use of hypocholesterolemia agent such as niacin, fibrates or any statin should be discontinued at least 7 days prior to study registration.
  • Personal or family history of hereditary muscular disorders
  • Previous history of muscular toxicity with another HMG-CoA reductase inhibitor
  • Alcohol abuse
  • Any condition that could affect absorption of study oral drugs (erlotinib and rosuvastatin)
  • Inflammatory bowel disease
  • Uncontrolled hypothyroidism
  • Chronic liver disease (ex: biliary sclerosis)
  • Suffering from infection with HIV, Tuberculosis, Hepatitis C or Hepatitis
  • Inability to give written, informed consent prior to study participation.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • The Ottawa Hospital Cancer Centre

    Ottawa, Ontario, K1H 8L6

Other trials in Canada

About this study

Official title: A Phase I, Dose Finding Study of the Combination of High-dose Statin Agent (Rosuvastatin) With Erlotinib in Patients With Advanced Solid Malignancies, With a Focus on Squamous Cell Carcinomas and NSCLC.

The purpose of this study is to determine the recommended phase II dose (RP2D) of rosuvastatin that can be given in combination with standard erlotinib treatment in patients with advanced incurable squamous cell cancer and NSCLC.

Read the detailed description

Cytotoxic chemotherapy remains the mainstay of anti-cancer medical treatment for the vast majority of patients with locally advanced or metastatic squamous cell cancers. However, curative success remains low and most patients eventually succumb to the disease or its complications. Moreover, cytotoxic chemotherapy is frequently associated with severe unwanted side effects. Therefore, in this patient population the unmet therapeutic need is high and new treatment is required.

Statins are drugs which inhibit the cellular mevalonate pathway and are conventionally used in the treatment of hypercholesterolemia in cardiovascular disorders. Increasing evidence suggests that statins might be used for cancer prevention/treatment through their interactions with essential cellular functions, such as cell proliferation and differentiation. Recent in vitro data indicate that statins induce growth arrest and apoptosis, inhibit secretion of proteolytic enzymes, reduce invasiveness and inhibit angiogenesis. These effects contribute to the reduction of tumor growth and metastases in preclinical in vivo models of a variety of tumors suggesting that statins may be useful in anticancer therapy. Studies previously performed by our group demonstrated that targeting the mevalonate pathway can induce tumor specific cytotoxicity in a number of tumor types that included squamous cell carcinomas, myeloid leukemia and a variety of pediatric cancers. Additionally, several clinical trials have also assessed the antitumor activity of statins.

Pre-clinically, we have demonstrated additive cytotoxic effects when combining lovastatin with tyrosine kinase inhibitors of the Epidermal Growth Factor Receptor (EGFR) in HNSCC cells (AG1478) and in 8 squamous cell carcinomas (gefitinib). Mechanistically, lovastatin treatment inhibited EGF induced EGFR autophosphorylation by 24hrs and showed co-operative targeting of the EGFR in combination with gefitinib. Taken together, these results demonstrate that targeting the mevalonate pathway can inhibit EGFR function and suggest the potential utility of combining these classes of drugs (i.e. an EGFR tyrosine kinase inhibitor and a statin).

The use of lovastatin is not optimal due to greatly enhanced toxicity with drugs such as gefitinib and erlotinib that are simultaneously metabolized by the same enzyme (cytP450A4). In contrast, rosuvastatin a relatively novel potent mevalonate pathway inhibitor is not metabolized significantly by cytP450A4. Due to the enhanced clinical activity of erlotinib in comparison to other EGFR tyrosine kinase inhibitors, the combination of erlotinib and rosuvastatin appears ideal.

Being tested
Erlotinib + Rosuvastatin
Keywords
Rosuvastatin, Erlotinib, Squamous Cell Carcinoma, Nom-Small Cell Lung Cancer
Medical subject headings
Carcinoma, Squamous Cell, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Erlotinib + RosuvastatinDrug

    Also called Tarceva, Crestor

    Patients will receive Erlotinib 150mg po daily. They will also receive Rosuvastatin at escalating dose levels starting at 1mg/kg po daily for 3 weeks, followed by a 1-week rest period. Patients may continue to receive rosuvastatin and erlotinib in the absence of disease progression or unacceptable toxicity.

Study groups in NCT00966472
Study groupRoleWhat they receive
Erlotinib + RosuvastatinExperimentalTo determine the recommended phase II dose (RP2D) of rosuvastatin that can be given in combination with standard erlotinib treatment in patients with advanced incurable squamous cell cancer and NSCLC.
Receives: Drug: Erlotinib + Rosuvastatin

What is being measured

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

  1. To determine the RPTD of rosuvastatin given orally daily x 3 weeks then 1 week off (28-day cycle) in combination with erlotinib given orally daily in patients with advanced solid tumors, especially squamous cell carcinomas and NSCLC.

    To determine the RPTD of rosuvastatin

    Measured: Within 6 months

Secondary outcomes (2)

  1. To determine the safety, tolerability, toxicity profile, dose limiting toxicities and PK profile of rosuvastatin and erlotinib when given as combination therapy.

    To determine the safety, tolerability, toxicity profile, dose limiting toxicities

    Measured: Within 6 months

  2. To perform preliminary assessment of the anti-tumor activity of rosuvastatin in combination with erlotinib in patients with measurable disease.

    To perform preliminary assessment of the anti-tumor activity

    Measured: Within one year

Timeline

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

  1. First posted27 Aug 2009 (estimated)
  2. Study startMar 2009
  3. Primary completionSep 2014
  4. Study completionSep 2014

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00966472
Sponsor's protocol ID
2007908-01H (OTT 08-07)
Status last verified
Apr 2020
First submitted
26 Aug 2009
Last updated
21 Apr 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Goss GD, Jonker DJ, Laurie SA, Weberpals JI, Oza AM, Spaans JN, la Porte C, Dimitroulakos J. A phase I study of high-dose rosuvastatin with standard dose erlotinib in patients with advanced solid malignancies. J Transl Med. 2016 Mar 31;14:83. doi: 10.1186/s12967-016-0836-6.

    PubMed 27036206

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Erlotinib + Rosuvastatin in people with Squamous Cell Carcinoma and Non-Small Cell Lung Cancer, run by Ottawa Hospital Research Institute at 1 site in Canada.

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 12 inclusion and 18 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 21 Apr 2020. 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 Canada. 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 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.

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?

To determine the RPTD of rosuvastatin given orally daily x 3 weeks then 1 week off (28-day cycle) in combination with erlotinib given orally daily in patients with advanced solid tumors, especially squamous cell carcinomas and NSCLC. (time frame: Within 6 months). 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 NCT00966472, which also lists 1 linked publication.

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 21 Apr 2020.

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