NLP SNP

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 Peritoneal Cavity Cancer Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: cytoreductive surgery

MeSH: Peritoneal Neoplasms Fever

HPO: Fever

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

2 Phase II(Window) Preoperative Study of Olaparib With Cisplatin or With Durvalumab (MEDI4736) or Alone or no Treatment in Patients With Histologically Proven Squamous Cell Carcinoma of the Head and Neck Who Are Candidates for Surgery.

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.

NCT02882308 Squamous Cell Carcinoma of the Head and Neck Drug: Olaparib Drug: Cisplatin Drug: Olaparib Drug: Durvalumab

MeSH: Carcinoma Carcinoma, Squamous Cell Squamous Cell Carcinoma of Head and Neck

HPO: Carcinoma Squamous cell carcinoma

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