REFGCT: A Phase II Study of Two Drugs for Relapsed or Refractory Malignant Germ Cell Tumors

A Phase II Study of Sirolimus and Erlotinib in Recurrent and Refractory Germ Cell Tumors

Categories:

Solid Tumor

Phase I/II

Diseases Treated:

Refractory and recurrent solid tumors

Eligibility Overview:

  • Participant is between 1-25 years old e at the time of enrollment (Note:  eligibility up to age 50 years for other participating sites).
  • Participant has had histologic verification of an extracranial germ cell tumor that is not a pure teratoma (mature or immature), pure germinoma, or pure seminoma.
  • Participant has relapsed or refractory disease following at least two prior platinum-containing chemotherapy regimens.
  • Patients must have measurable disease, documented according to RECIST criteria, or evaluable disease with a standard tumor marker (AFP and/or HCG) greater than 10 times the upper limit of normal.
  • Other requirements for this study.

Description

This research study is enrolling participants who have a malignant (cancerous) germ cell tumor that has come back after treatment (recurrent) or did not respond to treatment (refractory). Recurrent or resistant malignant germ cell tumors are commonly treated with a combination of surgery and chemotherapy. Some doctors might recommend high dose chemotherapy followed by bone stem cell transplantation. Although several treatment plans have been used none are considered to be the standard. The doctors in this study will be using two (2) drugs called sirolimus and erlotinib. These two (2) drugs will be used in combination. The doctors are using these drugs because they block the growth of specific proteins which are felt to be important in how germ cell tumors grow. Sirolimus has been approved by the Food and Drug Administration (FDA) to prevent rejection of kidney transplants in patients over thirteen (13) years of age, but has not been approved to treat cancer in adults or children. Erlotinib is approved by the FDA to treat adults with some types of lung and pancreatic cancers, but has not been approved to treat any cancers in children. The combination of sirolimus and erlotinib has been given to both adults and children who have brain tumors in clinical trials, but has never been given together to patients with germ cell tumors.

Goals

  • To find out if sirolimus and erlotinib will be an effective treatment for relapsed or refractory malignant germ cell tumors
  • To learn more about the side effects of the drug combination
  • To perform laboratory research studies on blood and tumor tissue to learn more about the biology of germ cell tumors and the effect of these drugs on the body

Inclusion criteria: (among others)

  • Participant is greater than twelve (12) months and less than twenty-five (25) years (at St. Jude) of age at the time of enrollment (Note:  eligibility up to age fifty (50) years for other participating sites).
  • Participant has had histologic verification of an extracranial germ cell tumor that is not a pure teratoma (mature or immature), pure germinoma, or pure seminoma.
  • Participant has relapsed or refractory disease following at least two prior platinum-containing chemotherapy regimens.
  • Patients must have measurable disease, documented according to RECIST criteria, or evaluable disease with a standard tumor marker (AFP and/or HCG) greater than 10 times the upper limit of normal.
  • Participant’s life expectancy is greater than eight (8) weeks.
  • Participant is greater than seven  (7) days since treatment with hematopoietic growth factor (greater than fourteen (14) days for Neulasta)
  • Participant is greater than forty-two (42) days since completion of any immunotherapy (i.e., tumor vaccines).
  • Participant is greater than two (2) weeks since most recent palliative RT.

Exclusion criteria: (among others)

  • Participant has active brain metastases (lethal intratumoral hemorrhages have been reported with erlotinib therapy). (Note: Patient has brain metastasis that has been treated and stable for thirty (30) days following treatment are eligible).
  • Participant is currently receiving another investigational drug.
  • Participant is currently receiving other anti-cancer agents.
  • Participant has an uncontrolled infection.
  • Participant has smoked within ten (10) days prior to enrollment and will not agree to not smoke for the duration of therapy (Note: smoking induces CYP3A4/5 enzymes and decreases exposure to sirolimus and erlotinib).
  • Participant has had major surgery within three (3) weeks prior to enrollment. (Note: procedures such as placement of a central vascular catheter, or limited tumor biopsy, are not considered major surgery).
  • Patients who have received prior therapy targeting EGFR with small molecule tyrosine kinase inhibitors or monoclonal antibodies are NOT eligible.
  • Prior treatment with mTOR or TORC1/2 inhibitors (eg, rapamycin, temsirolimus, everolimus, deferolimus) is NOT allowed.
  • Patients who are unable to swallow erlotinib tablets are not eligible.

For the current eligibility status of this clinical study, referring physicians must contact St. Jude Children's Research Hospital at 1-866-2ST-JUDE (1-866-278-5833).

Contact

Mark Hatley, MD, PhD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334

Referring or consulting clinicians only: protocolinfo@stjude.org
For all other inquiries about St. Jude Children's Research Hospital studies: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.