RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil,
work in different ways to stop the growth of tumor cells, either by killing the cells or by
stopping them from dividing. Hyperthermia therapy kills tumor cells by heating them to
several degrees above normal body temperature. Peritoneal infusion of heated and nonheated
chemotherapy drugs after surgery may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of hyperthermic
intraperitoneal oxaliplatin followed by intraperitoneal leucovorin and fluorouracil in
treating patients with peritoneal cancer.
NCT00625092 Conditions
- Peritoneal Cavity Cancer
Interventions
- Drug: fluorouracil
- Drug: leucovorin calcium
- Drug: oxaliplatin
- Procedure: cytoreductive surgery
The infusion will be repeated on day 2.
Blood samples are collected prior to surgery for pharmacogenetic studies and analyzed for the
presence of genetic polymorphisms in the XPD and XRCC1 DNA repair genes and the GSTP1 and
GSTM1 glutathione-S-transferase enzymes (i.e., XPD, Asp312Asn, XPD K751Q, XRCC1 Arg399GIn,
XRCC1 Arg399Q, GSTP1 l105V, and GSTM1 DEL). --- Asp312Asn --- --- K751Q ---
Primary Outcomes
Measure: Maximum tolerated dose of hyperthermic intraperitoneal oxaliplatin Time: 30 Days Post Treatment
Secondary Outcomes
Description: Using the Functional Assessment of Cancer Therapy for Colorectal Cancer (FACT-C) and SF-36 (Quality of Life Evaluation in Dialysis Patients) questionnaires, the quality of life following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPC) will be reported and compared to the preoperative baseline.
Measure: Changes in quality-of-life
Time: Baseline and at 4, 8, and 12 months
Measure: Overall survival
Time: 1 Year and 5 Years
Measure: Time to Disease Progression
Time: Monthly
OPHELIA (OPHELIA (OlaParib and durvalumab in HEad and neck squamous celL carcInomA) trial is
a Greek, investigator-initiated, randomized open-label window-of-opportunity phase II study.
Patients with operable histologically documented squamous-cell carcinoma of the oral cavity,
oropharynx, hypopharynx or larynx will be randomized between combination with durvalumab and
olaparib, cisplatin and olaparib, monotherapy with olaparib or no treatment, before starting
standard treatment.
Single-nucleotide polymorphisms:ERCC2 Lys751Gln (T/G). --- Lys751Gln ---
Single-nucleotide polymorphisms: XPD Lys751Gln (A/C, C/C). --- Lys751Gln ---
Primary Outcomes
Measure: Investigation of the change in the tumour Ki-67 before and after treatment with the combination of olaparib + durvalumab or olaparib + cisplatin or olaparib monotherapy. Time: At baseline and at the day of the surgery or 2nd biopsy (at days 23-29 days)
Secondary Outcomes
Measure: Objective response rate according to RECIST 1.1 criteria Time: Imaging studies will be performed at baseline and on week 4
Measure: Pathologic complete response rate Time: On week 4 only for operable patients
Measure: Metabolic response rate assessed by FDG-PET/CT scan (optional) Time: At baseline, on week 4
Measure: Number of participants with tolerability to the treatment. Time: From the 1st day of therapy and every week for 4 weeks maximum and 90 days after last therapy administration
Measure: Surgical complication rate Time: Up to 30 days after surgery or the day of initiation of the next anticancer therapy
Measure: Mutations in genes associated with DNA repair Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)
Measure: Expression of tissue biomarker: PARP1 Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)
Measure: Expression of tissue biomarker: BRACA1,2 Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)
Measure: Expression of tissue biomarker: ERCC1 Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)
Measure: Expression of tissue biomarker: PDL-1 Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)
Measure: Expression of tissue biomarker: TILs Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)
Measure: Plasma methylation biomarker: PARP1 methylation in plasma cell-free DNA Time: At baseline, a day before surgery and 90 days after surgery
Measure: Plasma methylation biomarker: BRCA1,2 methylation in plasma cell-free DNA Time: At baseline, a day before surgery and 90 days after surgery
Measure: Plasma methylation biomarker: ERCC1 methylation in plasma cell-free DNA Time: At baseline, a day before surgery and 90 days after surgery
Measure: Plasma methylation biomarker: RAD51C methylation in plasma cell-free DNA Time: At baseline, a day before surgery and 90 days after surgery
Measure: Single-nucleotide polymorphisms: PARP-1 Val762Ala Time: Sample will be collected once at baseline
Measure: Single-nucleotide polymorphisms: ERCC1 Asn118Asn (C/T) Time: Sample will be collected once at baseline
Measure: Single-nucleotide polymorphisms:ERCC2 Lys751Gln (T/G) Time: Sample will be collected once at baseline
Measure: Single-nucleotide polymorphisms: GSTP1 Ile105Val (A/G) Time: Sample will be collected once at baseline
Measure: Single-nucleotide polymorphisms: XPD Lys751Gln (A/C, C/C) Time: Sample will be collected once at baseline
Measure: Single-nucleotide polymorphisms: XRCC1 Arg399Gln (G/A) Time: Sample will be collected once at baseline
Measure: Circulating tumor cells (CTCs) evaluated for DNA repair biomarkers Time: At baseline, a day before surgery and 90 days after surgery
Measure: Circulating tumor cells (CTCs) evaluated for PD-L1 Time: At baseline, a day before surgery and 90 days after surgery