Temsirolimus (Torisel®) and Erlotinib (Tarceva®) in Platinum-Refractory/Ineligible, Advanced, Squamous Cell Carcinoma
Condition: Squamous Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Squamous Cell
Intervention: Erlotinib; Temsirolimus
Intervention description: Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of informed consent.; In the absence of Grade 3 or higher toxicity, a single, intra-patient dose increase of temsirolims to 20 mg intravenously weekly is permitted after the first 28 day cycle. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of informed consent.
Intervention MeSH terms: Sirolimus; Erlotinib Hydrochloride; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: squamous cell carcinoma; head; neck; aerodigestive

Summary:

      The primary hypothesis of this study is that the addition of mammalian target of rapamycin
      (mTOR) blockade to conventional epidermal growth factor receptor (EGFR) blockade will result
      in synergistic clinical activity in Squamous Cell Carcinoma of the Head and Neck (SCCHN),
      consistent with preclinical xenograft data. Patients will be treated with the combination of
      temsirolimus and erlotinib, at the previously established Maximal Tolerated Dose (MTD). The
      primary signal of efficacy will be progression free survival (PFS), anticipating that PFS
      will be prolonged compared to historical PFS in SCCHN patients treated with erlotinib or
      cetuximab monotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically or cytologically confirmed squamous cell carcinoma of the head and
             neck, from any primary site. Nasopharyngeal carcinoma, World Health Organization (WHO)
             Grade I, will be included.

          2. Advanced disease, fulfilling one of the criteria defined below:

               -  Incurable disease as assessed by surgical or radiation oncology

               -  Metastatic (M1) disease

               -  Persistent or progressive disease following curative-intent radiation, and not a
                  candidate for surgical salvage due to incurability or morbidity

          3. Platinum-refractory or platinum-ineligible, fulfilling one of the criteria defined
             below:

               -  disease progression during or after 4-6 cycles of platinum-containing therapy in
                  the advanced setting

               -  disease progression within 6 months of curative-intent treatment, which included
                  platinum-based chemotherapy

               -  ineligible for platinum-containing therapy, in the opinion of the medical
                  oncologist, due to medical comorbidities or unacceptable risk for toxicity

               -  patient refuses platinum-containing therapy

          4. Measurable disease based on response evaluation criteria in solid tumors (RECIST)

             - disease in previously irradiated sites is considered measurable if there has been
             unequivocal progression of the lesion after radiotherapy, or the lesion contains
             residual carcinoma by biopsy more than 6 weeks after completion of radiotherapy

          5. Easter Cooperative Oncology Group (ECOG) performance status 0-2 at time of informed
             consent

          6. Adequate hematologic reserve and organ function

               -  Absolute neutrophil count > 1200/µl

               -  Platelet count > 100,000/µl

               -  Renal function: Serum Creatinine ≤ 1.5x upper limit of normal (ULN)

               -  Liver function: Total bilirubin ≤ 1.5x ULN, Aspartate aminotransferase (AST) and
                  alanine aminotransferase (ALT) ≤ 2.5x ULN

          7. Able to provide written, voluntary consent

          8. Patients with reproductive potential must use an effective contraceptive method.

          9. Male or female, age ≥ 18 years

         10. Life expectancy ≥ 12 weeks

        Exclusion Criteria:

          1. Nasopharyngeal primary site, if WHO grade II or III

          2. Prior treatment blocking the epidermal growth factor receptor (EGFR), in the advanced
             disease setting

          3. Prior treatment blocking EGFR in the curative-intent setting, if delivered in the
             previous 6 months

          4. Prior treatment with a drug blocking the mammalian target of rapamycin (mTOR)

          5. Sensitivity to temsirolimus or erlotinib

          6. Uncontrolled metastatic disease of the central nervous system

          7. Radiotherapy within the 2 weeks before Cycle 1' Day 1

          8. Surgery within the 2 weeks before Cycle 1' Day 1

          9. Pregnant or lactating females

         10. Myocardial infarction or ischemia within the 6 months preceding study treatment

         11. Any co morbid condition that' in the view of the attending physician' renders the
             patient at high risk from treatment complications

         12. No other concurrent, investigational anti-neoplastic agent will be permitted

         13. History of prior malignancy within the prior five years, with the exception of
             non-melanoma carcinomas of the skin, and carcinoma in situ of the cervix